Paradoxically, the immune system can both benefit and antagonise the growth of cancer. Therefore, understanding how the cells of the immune system interact with the cancer microenvironment is of crucial importance. In their updated seminal review 'Hallmarks of Cancer: The Next Generation', Hanahan and Weinberg underline the importance of 'Avoiding immune destruction' and 'Tumour-promoting inflammation' to cancer biology. The immune cell compartment of cancer is composed of tissue resident immune cells and leukocytes that infiltrate from the circulation. The development of the cancer immune environment is inherently dynamic and the processes that regulate immune cell recruitment and function are not well understood. In recent years, the field has discovered that immune cells play roles in initiation of primary tumours, tumour maintenance and growth, and in aiding cancer metastasis. Recent success in directing and strengthening the immune system's anti-cancer functions (e.g. Tumour Infiltrating Lymphocyte; TIL therapy and immune check-point inhibition) highlight the potential for new therapies that can come from better understanding of how leukocytes are (dys)regulated in inflammation and cancer. However, current tumour immunotherapy strategies do not work for all patients or cancers.
Left: 3D imaging of lung adenocarcinoma. Tumour (green), large blood vessels (red), bronchioles (magenta), perivascular space (yellow). Right: neutrophils in the vasculature of the lung
We aim to better understand the immune system's role at the sites of primary tumour development and at the sites of cancer metastasis. All tumours have some influence on the local vasculature, either modifying it to meet their own needs or using it as a route to spread throughout the body. This has important consequences for our understanding of how the cells of the immune interact with the vasculature. Since it was first studied by microscopy more than 120 years ago, leukocyte extravasation has been refined in molecular detail in the post-capillary vessels, the major sites of immune cell infiltration in many (but, importantly, not all) anatomic sites. The way that leukocytes interact with the specialised vasculature of the lung, spleen, bone marrow, tumour co-opted vasculature and tumour neovasculature are relatively understudied often due to the technical difficulties of imaging some of these vascular beds. Due to the heterogeneity of the vasculature, these are exactly the areas that are least likely to fit the paradigms of leukocyte adhesion and transmigration established in the post-capillary venules. More recently, several innovative techniques have been developed to address these specialised sites by microscopy. This has helped to further investigate mechanisms of immune cell regulation, e.g. showing how immune cells interact with each other at sites of infection or injury to allow fine-tuning of the immune response and a greater portfolio of immune functions to be achieved. Therefore, a thorough examination of the localisation and regulation of leukocytes in situ is a clear unmet need to understand the fundamental mechanisms underlying onco-immunology.
We use advanced light microscopy in combination with other experimental approaches (flow cytometry, proteomics, transcriptomics) to better understand how the regulation of leukocyte dynamics contributes to the tumour environment in the context of both 'avoiding immune-destruction' and 'tumour-promoting inflammation'. Recent data point to multiple levels of immune regulation in cancer development and progression that parallel or redirect pathways that also mediate immune cell homeostasis and inflammation. Our overarching goal is to better understand how cancer evades and exploits the fundamental mechanisms of immune regulation and use this information to uncover new or better therapeutic strategies.
pdf Carlin Lab Report (299 KB)
Mackey JBG, McFarlane AJ, Jamieson T, Jackstadt R, Raffo-Iraolagoitia XL, Secklehner J, Cortes-Lavaud X, Fercoq F, Clarke W, Hedley A, Gilroy K, Lilla S, Vuononvirta J, Graham GJ, De Filippo K, Murphy DJ, Steele CW, Norman JC, Bird TG, Mann DA, Morton JP, Zanivan S, Sansom OJ, Carlin LM. Maturation, developmental site, and pathology dictate murine neutrophil function. bioRxiv. 2021.
McFarlane AJ, Fercoq F, Coffelt SB, Carlin LM. Neutrophil dynamics in the tumor microenvironment. J Clin Invest. 2021;131: ed2021.
Mackey JBG, Coffelt SB, Carlin LM. Neutrophil Maturity in Cancer. Frontiers in immunology. 2019; 10: 1912.
Carlin LM, Stamatiades EG, Auffray C, Hanna RN, Glover L, Vizcay-Barrena G, Hedrick CC, Cook HT, Diebold S, Geissmann F Nr4a1-dependent Ly6Clow monocytes monitor endothelial cells and orchestrate their disposal. Cell. 2013; 153: 362-75. (cover image).
2004: PhD, Imperial College London, Supervisor Dan Davis
2000: BSc (Hons) Immunology, University College London
2016-present: Group Leader/Head, Beatson Advanced Imaging Resource (BAIR), CRUK Scotland Institute, Glasgow
2013-2016: Lecturer in Respiratory Science/Group Leader, Imperial College London
2009-2013: Postdoctoral Fellow with Frédéric Geissmann, King's College London
2005-2009: Postdoctoral Fellow with Tony Ng, King's College London
Derby SJ, Dutton L, Strathdee KE, Stevenson K, Koessinger A, Jackson M, Tian Y, Yu W, McLay K, Misquitta J, Alsharif S, Clarke CJ, Gilmour L, Thomason P, McGhee E, McGarrity-Cottrell CL, Vanderlinden A, Collis SJ, Rominyi O, Lemgruber L, Solecki G, Olson M, Winkler F, Carlin LM, Heiland DH, Inman GJ, Chalmers AJ, Norman JC, Carruthers R, Birch JL. Inhibition of ATR opposes glioblastoma invasion through disruption of cytoskeletal networks and integrin internalization via macropinocytosis. Neuro Oncol. 2024;26(4):625-639.
Fercoq F, Cairns GS, Donatis MD, Mackey JBG, Floerchinger A, McFarlane A, Raffo-Iraolagoitia XL, Whyte D, Arnott LWG, Nixon C, Wiesheu R, Kilbey A, Brown L, Al-Khalidi S, Norman JC, Roberts EW, Blyth K, Coffelt SB, Carlin LM. Integrin inactivation slows down neutrophils congesting the pre-metastatic lung in a model of breast cancer. bioRxiv. 2024:2024.2003.2019.585724.
Fetit R, McLaren A, White M, Mills ML, Falconer J, Cortes-Lavaud X, Gilroy K, Lannagan TR, Ridgway RA, Nixon C, Naiker V, Njunge R, Clarke CJ, Whyte D, Kirschner K, Jackstadt R, Norman JC, Carlin LM, Campbell AD, Sansom OJ, Steele CW. Characterising neutrophil subtypes in cancer using scRNA sequencing demonstrates the importance of IL-1β/CXCR2 axis in generation of metastasis specific neutrophils. Cancer Res Commun. 2024.
Li C, Liu Q, Han L, Immler R, Rathkolb B, Secklehner J, Angelis MHd, Yildirim AÖ, Nicke A, Carlin LM, Sperandio M, Stoeger T, Rehberg M. eATP/P2X7R axis drives nanoparticle induced neutrophil recruitment in the pulmonary microcirculation. bioRxiv. 2024:2024.2003.2011.584398.
Matchett KP, Wilson-Kanamori JR, Portman JR, Kapourani CA, Fercoq F, May S, Zajdel E, Beltran M, Sutherland EF, Mackey JBG, Brice M, Wilson GC, Wallace SJ, Kitto L, Younger NT, Dobie R, Mole DJ, Oniscu GC, Wigmore SJ, Ramachandran P, Vallejos CA, Carragher NO, Saeidinejad MM, Quaglia A, Jalan R, Simpson KJ, Kendall TJ, Rule JA, Lee WM, Hoare M, Weston CJ, Marioni JC, Teichmann SA, Bird TG, Carlin LM, Henderson NC. Multimodal decoding of human liver regeneration. Nature. 2024.
Santi A, Kay EJ, Neilson LJ, McGarry L, Lilla S, Mullin M, Paul NR, Fercoq F, Koulouras G, Rodriguez Blanco G, Athineos D, Mason S, Hughes M, Thomson G, Kieffer Y, Nixon C, Blyth K, Mechta-Grigoriou F, Carlin LM, Zanivan S. Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Sci Signal. 2024;17(827):eade0580.
Whyte D, Voorde JV, Sumpton D, Dhayade S, Dornier E, Moore M, Novo D, Peters J, Wiesheu R, Mackey JBG, McFarlane AJ, Fercoq F, Fisher S, Caballero CD, Gilroy K, Redmond KL, Mitchell LE, Anderson E, Thomson G, Dzierozynski LN, Saab JJA, Lewis CA, Muir A, Halbrook CJ, Strathdee D, Jackstadt R, Nixon C, Dunne P, Steele CW, Carlin LM, Macpherson IR, Roberts EW, Coffelt SB, Blyth K, Sansom OJ, Norman JC, Clarke CJ. Uridine Phosphorylase-1 supports metastasis of mammary cancer by altering immune and extracellular matrix landscapes of the lung. bioRxiv. 2024:2024.2007.2002.601676.
Farahmand P, Gyuraszova K, Rooney C, Raffo-Iraolagoitia XL, Jayasekera G, Hedley A, Johnson E, Chernova T, Malviya G, Hall H, Monteverde T, Blyth K, Duffin R, Carlin LM, Lewis D, Le Quesne J, MacFarlane M, Murphy DJ. Asbestos accelerates disease onset in a genetic model of malignant pleural mesothelioma. Frontiers in Toxicology. 2023;5.
Hewitt RJ, Puttur F, Gaboriau DCA, Fercoq F, Fresquet M, Traves WJ, Yates LL, Walker SA, Molyneaux PL, Kemp SV, Nicholson AG, Rice A, Roberts E, Lennon R, Carlin LM, Byrne AJ, Maher TM, Lloyd CM. Lung extracellular matrix modulates KRT5(+) basal cell activity in pulmonary fibrosis. Nat Commun. 2023;14(1):6039.
Raffo-Iraolagoitia XL, McFarlane AJ, Kruspig B, Fercoq F, Secklehner J, Donatis MD, Mackey JBG, Wiesheu R, Laing S, Hsieh Y-C, Shaw R, Corbyn R, Nixon C, Miller C, Kirschner K, Bain CC, Daniel J. Murphy, Seth B. Coffelt, Carlin LM. γδ T cells impair airway macrophage differentiation in lung adenocarcinoma. bioRxiv. 2023:2023.2009.2014.557344.
Santi A, Kay EJ, Neilson LJ, McGarry L, Lilla S, Mullin M, Paul NR, Fercoq F, Koulouras G, Blanco GR, Athineos D, Mason S, Hughes M, Kieffer Y, Nixon C, Blyth K, Mechta-Grigoriou F, Carlin LM, Zanivan S. Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. bioRxiv. 2023;Volume:2023.2001.2013.523951.
Schmidt T, Dabrowska A, Waldron JA, Hodge K, Koulouras G, Gabrielsen M, Munro J, Tack DC, Harris G, McGhee E, Scott D, Carlin Leo M, Huang D, Le Quesne J, Zanivan S, Wilczynska A, Bushell M. eIF4A1-dependent mRNAs employ purine-rich 5’UTR sequences to activate localised eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation. Nucleic Acids Research. 2023; 51: 1859–1879
Humpton TJ, Hock AK, Kiourtis C, De Donatis M, Fercoq F, Nixon C, Bryson S, Strathdee D, Carlin LM, Bird TG, Blyth K, Vousden KH. A noninvasive iRFP713 p53 reporter reveals dynamic p53 activity in response to irradiation and liver regeneration in vivo. Sci Signal. 2022;15:eabd9099.
Leslie J, Mackey JBG, Jamieson T, Ramon-Gil E, Drake TM, Fercoq F, Clark W, Gilroy K, Hedley A, Nixon C, Luli S, Laszczewska M, Pinyol R, Esteban-Fabró R, Willoughby CE, Haber PK, Andreu-Oller C, Rahbari M, Fan C, Pfister D, Raman S, Wilson N, Müller M, Collins A, Geh D, Fuller A, McDonald D, Hulme G, Filby A, Cortes-Lavaud X, Mohamed N-E, Ford CA, Raffo Iraolagoitia XL, McFarlane AJ, McCain MV, Ridgway RA, Roberts EW, Barry ST, Graham GJ, Heikenwälder M, Reeves HL, Llovet JM, Carlin LM, Bird TG, Sansom OJ, Mann DA. CXCR2 inhibition enables NASH-HCC immunotherapy. Gut. 2022;
Schmidt T, Dabrowska A, Waldron JA, Hodge K, Koulouras G, Gabrielsen M, Munro J, Tack DC, Harris G, McGhee E, Scott D, Carlin LM, Huang D, Le Quesne J, Zanivan S, Wilczynska A, Bushell M. Purine-rich RNA sequences in the 5’UTR site-specifically regulate eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation. bioRxiv. 2022;Volume:2022.2008.2008.503179.
Brownlie D, Doughty-Shenton D, Soong DY, Nixon C, Carragher NO, Carlin LM, Kitamura T. Metastasis-associated macrophages constrain antitumor capability of natural killer cells in the metastatic site at least partially by membrane bound transforming growth factor β. J Immunother Cancer. 2021;9:e001740
Juzenaite G, Secklehner J, Vuononvirta J, Helbawi Y, Mackey JBG, Dean C, Harker JA, Carlin LM, Rankin S, De Filippo K. Lung Marginated and Splenic Murine Resident Neutrophils Constitute Pioneers in Tissue-Defense During Systemic E. coli Challenge. Front Immunol. 2021;12:597595.
Mackey JBG, McFarlane AJ, Jamieson T, Jackstadt R, Raffo-Iraolagoitia XL, Secklehner J, Cortes-Lavaud X, Fercoq F, Clarke W, Hedley A, Gilroy K, Lilla S, Vuononvirta J, Graham GJ, De Filippo K, Murphy DJ, Steele CW, Norman JC, Bird TG, Mann DA, Morton JP, Zanivan S, Sansom OJ, Carlin LM. Maturation, developmental site, and pathology dictate murine neutrophil function. bioRxiv. 2021.
McCowan J, Fercoq F, Kirkwood PM, T'Jonck W, Hegarty LM, Mawer CM, Cunningham R, Mirchandani AS, Hoy A, Humphries DC, Jones GR, Hansen CG, Hirani N, Jenkins SJ, Henri S, Malissen B, Walmsley SR, Dockrell DH, Saunders PTK, Carlin LM, Bain CC. The transcription factor EGR2 is indispensable for tissue-specific imprinting of alveolar macrophages in health and tissue repair. Sci Immunol. 2021 Nov 19;6(65):eabj2132.
Ntala C, Salji M, Salmond J, Officer L, Teodosio AV, Blomme A, McGhee EJ, Powley I, Ahmad I, Kruithof-de Julio M, Thalmann G, Roberts E, Goodyear CS, Jamaspishvili T, Berman DM, Carlin LM, Le Quesne J, Leung HY. Analysis of Prostate Cancer Tumor Microenvironment Identifies Reduced Stromal CD4 Effector T-cell Infiltration in Tumors with Pelvic Nodal Metastasis. Eur Urol Open Sci. 2021;29:19-29.
Fercoq F, Carlin LM. "Mind the GAP": RGS1 hinders antitumor lymphocytes. Nat Immunol. 2021; 22:802-804.
McFarlane AJ, Fercoq F, Coffelt SB, Carlin LM. Neutrophil dynamics in the tumor microenvironment. J Clin Invest. 2021;131: ed2021.
Fercoq F, Remion E, Vallarino-Lhermitte N, Alonso J, Raveendran L, Nixon C, Le Quesne J, Carlin LM, Martin C. Microfilaria-dependent thoracic pathology associated with eosinophilic and fibrotic polyps in filaria-infected rodents. Parasit Vectors. 2020;13(1):551.
Leung EYL, Ennis DP, Kennedy PR, Hansell C, Dowson S, Farquharson M, Spiliopoulou P, Nautiyal J, McNamara S, Carlin LM, Fisher K, Davis DM, Graham G, McNeish IA. NK Cells Augment Oncolytic Adenovirus Cytotoxicity in Ovarian Cancer. Molecular therapy oncolytics. 2020; 16: 289-301.
Muthalagu N, Monteverde T, Raffo-Iraolagoitia X, Wiesheu R, Whyte D, Hedley A, Laing S, Kruspig B, Upstill-Goddard R, Shaw R, Neidler S, Rink C, Karim SA, Gyuraszova K, Nixon C, Clark W, Biankin AV, Carlin LM, Coffelt SB, Sansom OJ, Morton JP, Murphy DJ. Repression of the Type I Interferon pathway underlies MYC & KRAS-dependent evasion of NK & B cells in Pancreatic Ductal Adenocarcinoma. Cancer discovery. 2020;
Pillay J, Tregay N, Juzenaite G, Carlin LM, Pirillo C, Gaboriau DCA, Farahi N, Summers C, Lo Celso C, Chilvers ER, Rankin S, De Filippo K. Effect of the CXCR4 antagonist plerixafor on endogenous neutrophil dynamics in the bone marrow, lung and spleen. Journal of Leukocyte Biology. 2020; 107: 1175– 1185
Plant T, Eamsamarng S, Sanchez-Garcia MA, Reyes L, Renshaw SA, Coelho P, Mirchandani AS, Morgan JM, Ellett FE, Morrison T, Humphries D, Watts ER, Murphy F, Raffo-Iraolagoitia XL, Zhang A, Cash JL, Loynes C, Elks PM, Van Eeden F, Carlin LM, Furley AJW, Whyte MKB, Walmsley SR. Semaphorin 3F signaling actively retains neutrophils at sites of inflammation. The Journal of clinical investigation. 2020;130:3221-3237
Fercoq F, Remion E, Frohberger SJ, Vallarino-Lhermitte N, Hoerauf A, Le Quesne J, Landmann F, Hubner MP, Carlin LM, Martin C. IL-4 receptor dependent expansion of lung CD169+ macrophages in microfilaria-driven inflammation. PLoS neglected tropical diseases. 2019; 13: e0007691.
Mackey JBG, Coffelt SB, Carlin LM. Neutrophil Maturity in Cancer. Frontiers in immunology. 2019; 10: 1912.
McCormick B, Craig HE, Chu JY, Carlin LM, Canel M, Wollweber F, Toivakka M, Michael M, Astier AL, Norton L, Lilja J, Felton JM, Sasaki T, Ivaska J, Hers I, Dransfield I, Rossi AG, Vermeren S. A Negative Feedback Loop Regulates Integrin Inactivation and Promotes Neutrophil Recruitment to Inflammatory Sites. Journal of immunology. 2019;
Patel DF, Peiro T, Bruno N, Vuononvirta J, Akthar S, Puttur F, Pyle CJ, Suveizdyte K, Walker SA, Singanayagam A, Carlin LM, Gregory LG, Lloyd CM, Snelgrove RJ. Neutrophils restrain allergic airway inflammation by limiting ILC2 function and monocyte-dendritic cell antigen presentation. Science immunology. 2019; 4.
Puttur F, Denney L, Gregory LG, Vuononvirta J, Oliver R, Entwistle LJ, Walker SA, Headley MB, McGhee EJ, Pease JE, Krummel MF, Carlin LM, Lloyd CM. Pulmonary environmental cues drive group 2 innate lymphoid cell dynamics in mice and humans. Science immunology. 2019; 4.
Brown E, Carlin LM, Nerlov C, Lo Celso C, Poole, AW. Multiple membrane extrusion sites drive megakaryocyte migration into bone marrow blood vessels. Life Science Alliance. 2018; 1:
Duarte D, Hawkins ED, Akinduro O, Ang H, De Filippo K, Kong IY, Haltalli M, Ruivo N, Straszkowski L, Vervoort SJ, McLean C, Weber TS, Khorshed R, Pirillo C, Wei A, Ramasamy SK, Kusumbe AP, Duffy K, Adams RH, Purton LE et al. Inhibition of Endosteal Vascular Niche Remodeling Rescues Hematopoietic Stem Cell Loss in AML. Cell Stem Cell 2018; 22: 64-77 e6
Novo D, Heath N, Mitchell L, Caligiuri G, MacFarlane A, Reijmer D, Charlton L, Knight J, Calka M, McGhee E, Dornier E, Sumpton D, Mason S, Echard A, Klinkert K, et al. Mutant p53s generate pro-invasive niches by influencing exosome podocalyxin levels. Nat Commun 2018; 9: 5069
Riley JS, Quarato G, Cloix C, Lopez J, O'Prey J, Pearson M, Chapman J, Sesaki H, Carlin LM, Passos JF, Wheeler AP, Oberst A, Ryan KM, Tait SW. Mitochondrial inner membrane permeabilisation enables mtDNA release during apoptosis. EMBO J. 2018; 37: e99238.
Tung SL, Boardman DA, Sen M, Letizia M, Peng Q, Cianci N, Dioni L, Carlin LM, Lechler R, Bollati V, Lombardi G, Smyth LA. Regulatory T cell-derived extracellular vesicles modify dendritic cell function. Sci Rep. 2018; 8: 6065.
Irshad S, Flores-Borja F, Lawler K, Monypenny J, Evans R, Male V, Gordon P, Cheung A, Gazinska P, Noor F, Wong F, Grigoriadis A, Fruhwirth GO, Barber PR, Woodman N, Patel D, Rodriguez-Justo M, Owen J, Martin SG, Pinder SE et al. RORgammat(+) Innate Lymphoid Cells Promote Lymph Node Metastasis of Breast Cancers. Cancer Res 2017; 77: 1083-96
Karadjian G, Fercoq F, Pionnier N, Vallarino-Lhermitte N, Lefoulon E, Nieguitsila A, Specht S, Carlin LM, Martin C. Migratory phase of Litomosoides sigmodontis filarial infective larvae is associated with pathology and transient increase of S100A9 expressing neutrophils in the lung. PLoS Negl Trop Dis. 2017; 11: e0005596
Reid SE, Kay EJ, Neilson LJ, Henze AT, Serneels J, McGhee EJ, Dhayade S, Nixon C, Mackey JB, Santi A, Swaminathan K, Athineos D, Papalazarou V, Patella F, Roman-Fernandez A, ElMaghloob Y, Hernandez-Fernaud JR, Adams RH, Ismail S, Bryant DM et al. Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium. EMBO J 2017; 36: 2373-89
Secklehner J, Lo Celso C, Carlin LM. Intravital microscopy in historic and contemporary immunology. Immunol Cell Biol 2017; 95: 506-13
Integrins are cell adhesion receptors involved in mediating the invasive migration, growth and metastasis of cancer cells. Data from our lab and our collaborators has established that Rab-regulated integrin trafficking contributes to cancer cell migration.
Indeed, we have now obtained detailed descriptions of the molecular machinery of integrin transport and determined how this contributes to invasive migration of cancer cells through three-dimensional matrices.
Furthermore, we have identified components of the cell's machinery for processing and transporting mRNA that make key contributions to cancer cell invasion. We are currently evaluating the molecular components of these novel pathways as potential targets for anti-cancer therapy and patient screening strategies.
Christoforides C, Rainero E, Brown KK, Norman JC* and Toker A*. PKD Controls αvβ3 Integrin Recycling and Tumor Cell Invasive Migration Through its Substrate Rabaptin-5. Dev Cell. 2012; 23:560-572 *joint corresponding authors
Muller PA, Trinidad AG, Timpson P, Morton JP, Zanivan S, van den Berghe PV, Nixon C, Karim SA, Caswell PT, Noll JE, Coffill CR, Lane DP, Sansom OJ, Neilsen PM, Norman JC*, Vousden KH*. Mutant p53 enhances MET trafficking and signalling to drive cell scattering and invasion. Oncogene. 2013 32: 1252-65 *joint corresponding authors
Dozynkiewicz MA, Jamieson NB, Macpherson I, Grindlay J, van den Berghe PV, von Thun A, Morton JP, Gourley C, Timpson P, Nixon C, McKay CJ, Carter R, Strachan D, Anderson K, Sansom OJ, Caswell PT, Norman JC. Rab25 and CLIC3 Collaborate to Promote Integrin Recycling from Late Endosomes/Lysosomes and Drive Cancer Progression. Dev Cell. 2012; 17: 131-45
Rainero E, Caswell PT, Muller PA, Grindlay J, McCaffrey MW, Zhang Q, Wakelam MJ, Vousden KH, Graziani A, Norman JC. Diacylglycerol kinase α controls RCP-dependent integrin trafficking to promote invasive migration. J Cell Biology. 2012; 196: 277-295
von Thun A, Birtwistle M, Kalna G, Grindlay J, Strachan D, Kolch W and von Kriegsheim A, Norman JC. ERK2 drives tumour cell migration in 3D microenvironments by suppressing expression of Rab17 and Liprin-β2. J Cell Science. 2012; 125: 1465-77
1992: PhD, University of London
1985: BSc, Biochemistry, University of Southampton
2009-present: Senior Group Leader, CRUK Scotland Institute
2005-2009: Junior Group Leader, CRUK Beatson Institute
2000-2005: Lecturer, Dept. Biochemistry, University of Leicester
1999-2004: Wellcome Career Development Fellow, Dept. Biochemistry, University of Leicester
1996-1998: Postdoctoral Fellow, Dept. Biochemistry, University of Leicester
1994-1996: Postdoctoral Fellow, Physiological Laboratory, University of Cambridge
1992-1994: Postdoctoral Fellow, Dept. Physiology, University College London
Wellcome Trust Career Development Award, 1999-2004
Derby SJ, Dutton L, Strathdee KE, Stevenson K, Koessinger A, Jackson M, Tian Y, Yu W, McLay K, Misquitta J, Alsharif S, Clarke CJ, Gilmour L, Thomason P, McGhee E, McGarrity-Cottrell CL, Vanderlinden A, Collis SJ, Rominyi O, Lemgruber L, Solecki G, Olson M, Winkler F, Carlin LM, Heiland DH, Inman GJ, Chalmers AJ, Norman JC, Carruthers R, Birch JL. Inhibition of ATR opposes glioblastoma invasion through disruption of cytoskeletal networks and integrin internalization via macropinocytosis. Neuro Oncol. 2024;26(4):625-639.
Fercoq F, Cairns GS, Donatis MD, Mackey JBG, Floerchinger A, McFarlane A, Raffo-Iraolagoitia XL, Whyte D, Arnott LWG, Nixon C, Wiesheu R, Kilbey A, Brown L, Al-Khalidi S, Norman JC, Roberts EW, Blyth K, Coffelt SB, Carlin LM. Integrin inactivation slows down neutrophils congesting the pre-metastatic lung in a model of breast cancer. bioRxiv. 2024:2024.2003.2019.585724.
Fetit R, McLaren A, White M, Mills ML, Falconer J, Cortes-Lavaud X, Gilroy K, Lannagan TR, Ridgway RA, Nixon C, Naiker V, Njunge R, Clarke CJ, Whyte D, Kirschner K, Jackstadt R, Norman JC, Carlin LM, Campbell AD, Sansom OJ, Steele CW. Characterising neutrophil subtypes in cancer using scRNA sequencing demonstrates the importance of IL-1β/CXCR2 axis in generation of metastasis specific neutrophils. Cancer Res Commun. 2024.
Gounis M, Campos AV, Shokry E, Mitchell L, Dornier E, Rooney N, Dhayade S, Pardo L, Moore M, Novo D, Mowat J, Jamieson C, Kay E, Zanivan S, Nixon C, Macpherson I, Tardito S, Sumpton D, Blyth K, Norman JC, Clarke CJ. Metabolic adaptations of micrometastases alter EV production to generate invasive microenvironments. bioRxiv. 2024:2024.2005.2012.593552.
Whyte D, Voorde JV, Sumpton D, Dhayade S, Dornier E, Moore M, Novo D, Peters J, Wiesheu R, Mackey JBG, McFarlane AJ, Fercoq F, Fisher S, Caballero CD, Gilroy K, Redmond KL, Mitchell LE, Anderson E, Thomson G, Dzierozynski LN, Saab JJA, Lewis CA, Muir A, Halbrook CJ, Strathdee D, Jackstadt R, Nixon C, Dunne P, Steele CW, Carlin LM, Macpherson IR, Roberts EW, Coffelt SB, Blyth K, Sansom OJ, Norman JC, Clarke CJ. Uridine Phosphorylase-1 supports metastasis of mammary cancer by altering immune and extracellular matrix landscapes of the lung. bioRxiv. 2024:2024.2007.2002.601676.
Koessinger D, Novo D, Koessinger A, Campos A, Peters J, Dutton L, Paschke P, Zerbst D, Moore M, Mitchell L, Neilson M, Stevenson K, Chalmers A, Tait S, Birch J, Norman J. Glioblastoma extracellular vesicles influence glial cell hyaluronic acid deposition to promote invasiveness. Neuro-Oncology Advances. 2023;5:vdad067.
Moore M, Pardo L, Mitchell L, Schmidt T, May S, Mueller M, Strathdee D, Bryson S, Hodge K, Lilla S, Zanivan S, Waldron J, McGarry L, Peter-Durairaj R, Kanellos G, Nixon C, Ballantyne F, LeQuesne J, Sansom OJ, Bird T, Bushell M, Norman JC. The eIF4A2 negative regulator of mRNA translation promotes extracellular matrix deposition to accelerate hepatocellular carcinoma initiation. bioRxiv. 2023;Volume:2023.2008.2016.553544.
Nikolatou K, Sandilands E, Román-Fernández A, Cumming EM, Freckmann E, Lilla S, Buetow L, McGarry L, Neilson M, Shaw R, Strachan D, Miller C, Huang DT, McNeish IA, Norman JC, Zanivan S, Bryant DM. PTEN deficiency exposes a requirement for an ARF GTPase module for integrin-dependent invasion in ovarian cancer. The EMBO Journal. 2023;n/a:e113987.
Román-Fernández A, Mansour MA, Kugeratski FG, Anand J, Sandilands E, Galbraith L, Rakovic K, Freckmann EC, Cumming EM, Park J, Nikolatou K, Lilla S, Shaw R, Strachan D, Mason S, Patel R, McGarry L, Katoch A, Campbell KJ, Nixon C, Miller CJ, Leung HY, Le Quesne J, Norman JC, Zanivan S, Blyth K, Bryant DM. Spatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function. Sci Adv. 2023;9:eabq1858.
Waldron JA, Kanellos G, Smith RCL, Knight JRP, Munro J, Alexandrou C, Vlahov N, Pardo-Fernandez L, Moore M, Gillen SL, Strathdee D, Stevenson D, Warrander FC, Gilroy K, Nixon C, Cadden B, Powley I, Officer-Jones L, Ballantyne F, Hay J, Pennel K, Edwards J, Campbell AD, Ridgway RA, Coffelt SB, Norman J, Quesne JL, Bushell M, Sansom OJ. eIF4A1 is essential for reprogramming the translational landscape of Wnt-driven colorectal cancers. bioRxiv. 2023:2023.2011.2010.566546.
Wilson B, Flett C, Gemperle J, Lawless C, Hartshorn M, Hinde E, Harrison T, Chastney M, Taylor S, Allen J, Norman JC, Zacharchenko T, Caswell P. Proximity labelling identifies pro-migratory endocytic recycling cargo and machinery of the Rab4 and Rab11 families. J Cell Sci. 2023;136:jcs260468.
Jamshidiha M, Lanyon-Hogg T, Sutherell CL, Craven GB, Tersa M, De Vita E, Brustur D, Pérez-Dorado I, Hassan S, Petracca R, Morgan RM, Sanz-Hernández M, Norman JC, Armstrong A, Mann DJ, Cota E, Tate EW. Identification of the first structurally validated covalent ligands of the small GTPase RAB27A. RSC Med Chem. 2022;13:150-155.
Koessinger AL, Cloix C, Koessinger D, Heiland DH, Bock FJ, Strathdee K, Kinch K, Martínez-Escardó L, Paul NR, Nixon C, Malviya G, Jackson MR, Campbell KJ, Stevenson K, Davis S, Elmasry Y, Ahmed A, O’Prey J, Ichim G, Schnell O, Stewart W, Blyth K, Ryan KM, Chalmers AJ, Norman JC, Tait SWG. Increased apoptotic sensitivity of glioblastoma enables therapeutic targeting by BH3-mimetics. Cell Death & Differentiation. 2022; 29: 2089–2104
Koessinger D, Novo D, Birch J, Mitchell L, Moore M, Zerbst D, Chalmers A, Koessinger A, Stevenson K, Nielson M, Norman JC. Glioblastoma exosomes influence glial cell hyaluronic acid deposition to promote invasiveness. bioRxiv. 2022;
Närvä E, Taskinen ME, Lilla S, Isomursu A, Pietilä M, Weltner J, Isola J, Sihto H, Joensuu H, Zanivan S, Norman J, Ivaska J. MASTL is enriched in cancerous and pluripotent stem cells and influences OCT1/OCT4 levels. iScience. 2022;25:104459.
Nikolatou K, Sandilands E, Roman-Fernandez A, Cumming EM, Freckmann EC, Lilla S, Buetow L, McGarry L, Neilson M, Shaw R, Strachan D, Miller C, Huang DT, McNeish IA, Norman JC, Zanivan S, Bryant D. PTEN deficiency exposes a requirement for an ARF GTPase module in integrin-dependent invasion in ovarian cancer. bioRxiv. 2022;Volume:2022.2011.2029.518198.
Rathan-Kumar S, Roland JT, Momoh M, Goldstein A, Lapierre LA, Manning E, Mitchell L, Norman J, Kaji I, Goldenring JR. Rab11FIP1-Deficient Mice Develop Spontaneous Inflammation and Show Increased Susceptibility to Colon Damage. Am J Physiol Gastrointest Liver Physiol. 2022; 323:G239-G254
Mackey JBG, McFarlane AJ, Jamieson T, Jackstadt R, Raffo-Iraolagoitia XL, Secklehner J, Cortes-Lavaud X, Fercoq F, Clarke W, Hedley A, Gilroy K, Lilla S, Vuononvirta J, Graham GJ, De Filippo K, Murphy DJ, Steele CW, Norman JC, Bird TG, Mann DA, Morton JP, Zanivan S, Sansom OJ, Carlin LM. Maturation, developmental site, and pathology dictate murine neutrophil function. bioRxiv. 2021.
Marco S, Neilson M, Moore M, Perez-Garcia A, Hall H, Mitchell L, Lilla S, Blanco GR, Hedley A, Zanivan S, Norman JC. Nuclear-capture of endosomes depletes nuclear G-actin to promote SRF/MRTF activation and cancer cell invasion. Nat Commun. 2021 Nov 24;12(1):6829.
Nászai M, Bellec K, Yu Y, Román-Fernández A, Sandilands E, Johansson J, Campbell AD, Norman JC, Sansom OJ, Bryant DM, Cordero JB. RAL GTPases mediate EGFR-driven intestinal stem cell proliferation and tumourigenesis. Elife. 2021;10.
Phatak V, von Grabowiecki Y, Janus J, Officer L, Behan C, Aschauer L, Pinon L, Mackay H, Zanivan S, Norman JC, Kelly M, Le Quesne J, Muller PAJ. Mutant p53 promotes RCP-dependent chemoresistance coinciding with increased delivery of P-glycoprotein to the plasma membrane. Cell Death Dis. 2021;12(2):207.
Rabas N, Palmer S, Mitchell L, Ismail S, Gohlke A, Riley JS, Tait SWG, Gammage P, Soares LL, Macpherson IR, Norman JC. PINK1 drives production of mtDNA-containing extracellular vesicles to promote invasiveness. J Cell Biol. 2021;220:e202006049
Jackstadt R, Norman JC. Stromal WNTer Keeps the Tumor Cold and Drives Metastasis. Dev Cell. 2021;56:3-4.
Koessinger AL, Koessinger D, Stevenson K, Cloix C, Mitchell L, Nixon C, Gomez-Roman N, Chalmers AJ, Norman JC, Tait SWG. Quantitative in vivo bioluminescence imaging of orthotopic patient-derived glioblastoma xenografts. Scientific Reports. 2020;10(1):15361.
Sundararaman A, Fukushima Y, Norman JC, Uemura A, Mellor H. RhoJ Regulates α5β1 Integrin Trafficking to Control Fibronectin Remodeling during Angiogenesis. Current Biology. 2020; 30: 2146 - 2155.e5
Taskinen ME, Närvä E, Conway JRW, Hinojosa LS, Lilla S, Mai A, De Franceschi N, Elo LL, Grosse R, Zanivan S, Norman JC, Ivaska J. MASTL promotes cell contractility and motility through kinase-independent signaling. J Cell Biol. 2020; 219: e201906204.
Auciello FR, Bulusu V, Oon C, Tait-Mulder J, Berry M, Bhattacharyya S, Tumanov S, Allen-Petersen BL, Link J, Kendsersky ND, Vringer E, Schug M, Novo D, Hwang RF, Evans RM, Nixon C, Dorrell C, Morton JP, Norman JC, Sears RC, Kamphorst JJ, Sherman MH. A stromal lysolipid-autotaxin signaling axis promotes pancreatic tumor progression. Cancer Discov. 2019; 9: 617-627
Juin A, Spence HJ, Martin KJ, McGhee E, Neilson M, Cutiongco MFA, Gadegaard N, Mackay G, Fort L, Lilla S, Kalna G, Thomason P, Koh YWH, Norman JC, Insall RH, Machesky LM. N-WASP Control of LPAR1 Trafficking Establishes Response to Self-Generated LPA Gradients to Promote Pancreatic Cancer Cell Metastasis. Developmental cell. 2019; 51: 431-445
Linnane E, Davey P, Zhang P, Puri S, Edbrooke M, Chiarparin E, Revenko AS, Macleod AR, Norman JC, Ross SJ. Differential uptake, kinetics and mechanisms of intracellular trafficking of next-generation antisense oligonucleotides across human cancer cell lines. Nucleic Acids Res. 2019; 47: 4375–4392
Dornier E, Norman JC. Cancer cells with trapped nuclei cut their way through the extracellular matrix. Nat Commun 2018; 9: 3954
Novo D, Heath N, Mitchell L, Caligiuri G, MacFarlane A, Reijmer D, Charlton L, Knight J, Calka M, McGhee E, Dornier E, Sumpton D, Mason S, Echard A, Klinkert K, et al. Mutant p53s generate pro-invasive niches by influencing exosome podocalyxin levels. Nat Commun 2018; 9: 5069.
Diaz-Vera J, Palmer S, Hernandez-Fernaud JR, Dornier E, Mitchell LE, MacPherson I, Edwards J, Zanivan S, Norman JC. A proteomic approach to identify endosomal cargoes controlling cancer invasiveness. J Cell Sci 2017; 130: 697-711
Dornier E, Rabas N, Mitchell L, Novo D, Dhayade S, Marco S, Mackay G, Sumpton D, Pallares M, Nixon C, Blyth K, MacPherson I, Rainero E, Norman JC. Glutaminolysis drives membrane trafficking to promote cancer invasion. Nat Comms 2017; 8: 2255
Gundry C, Marco S, Rainero E, Miller B, Dornier E, Mitchell L, Caswell PT, Campbell AD, Hogeweg A, Sansom OJ, Morton JP, Norman JC. Phosphorylation of Rab-coupling protein by LMTK3 controls Rab14-dependent EphA2 trafficking to promote cell:cell repulsion. Nat Commun 2017; 8: 14646
Hall PS, Smith A, Hulme C, Vargas-Palacios A, Makris A, Hughes-Davies L, Dunn JA, Bartlett JMS, Cameron DA, Marshall A, Campbell A, Macpherson IR, Dan Rea, Francis A, Earl H, Morgan A, Stein RC, McCabe C; OPTIMA Trial Management Group. Value of information analysis of multiparameter tests for chemotherapy in early breast cancer: The OPTIMA Prelim Trial. Value Health 2017; 20: 1311-8
Hernandez-Fernaud JR, Ruengeler E, Casazza A, Neilson LJ, Pulleine E, Santi A, Ismail S, Lilla S, Dhayade S, MacPherson IR, McNeish I, Ennis D, Ali H, Kugeratski FG, Al Khamici H, van den Biggelaar M, van den Berghe PV, Cloix C, McDonald L, Millan D et al. Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity. Nat Commun 2017; 8: 14206
Dornier E, Norman JC. Tensin links energy metabolism to extracellular matrix assembly. J Cell Biol 2017; 216: 867-9
Norman J, Zanivan S. Chloride intracellular channel 3: A secreted pro-invasive oxidoreductase. Cell Cycle 2017; 16: 1993-4
Birch J, Clarke CJ, Campbell AD, Campbell K, Mitchell L, Liko D, Kalna G, Strathdee D, Sansom OJ, Neilson M, Blyth K, Norman JC. The initiator methionine tRNA drives cell migration and invasion leading to increased metastatic potential in melanoma. Biol Open. 2016; 5: 1371-9
Boulay PL, Mitchell L, Turpin J, Huot-Marchand JE, Lavoie C, Sanguin-Gendreau V, Jones L, Mitra S, Livingstone JM, Campbell S, Hallett M, Mills GB, Park M, Chodosh L, Strathdee D, Norman JC, Muller WJ. Rab11-FIP1C is a critical negative regulator in ErbB2-mediated mammary tumor progression. Cancer Res. 2016; 76: 2662-74
Clarke CJ, Berg TJ, Birch J, Ennis D, Mitchell L, Cloix C, Campbell A, Sumpton D, Nixon C, Campbell K, Bridgeman VL, Vermeulen PB, Foo S, Kostaras E, Jones JL, Haywood L, Pulleine E, Yin HB, Strathdee D, Sansom O Blyth K, McNeish I, Zanivan S, Reynolds AR, Norman JC. The initiator methionine tRNA drives secretion of type II collagen from stromal fibroblasts to promote tumor growth and angiogenesis. Curr Biol. 2016; 26: 755-65
Cassie Clarke
Vanessa Gonzalez
Luis Pardo-Fernandez
Madeleine Moore
Iain MacPherson
Sonam Ansel
Sophie Fisher
Jasmine Peters (joint with Ed Roberts)
Lucy Somerville
Colorectal cancer (CRC)—the third most common cancer in the UK and the second leading cause of cancer mortality—is a heterogeneous disease comprising distinct molecular subgroups that differ in their histopathological features, prognosis, and response to therapy. Despite advances in the detection and treatment of early-stage disease, patients with advanced, recurrent, or metastatic CRCs have few therapeutic options and a dismal prognosis. Utilising state-of-the-art preclinical models harbouring key driver mutations, our group is interrogating the molecular mechanisms underpinning CRC initiation, progression, response to therapy, and metastasis. Our overarching goals are to identify early-stage diagnostic biomarkers and develop stage- and subtype-specific targeted therapies.
As part of these efforts, we are major contributors to a number of large cancer consortia, with the aim of driving more effective therapeutic approaches in colorectal cancer. Our group leads a Europe-wide, CRUK-funded consortium of basic, translational, and clinical scientists (ACRCelerate—Colorectal Cancer Stratified Medicine Network) to identify new therapeutic targets for the different CRC subtypes and deliver molecular insights with the potential to inform clinical decision-making and patient stratification. Similarly, through participation in the CRUK Grand Challenge Rosetta consortium, we are working to therapeutically exploit the altered metabolic dependencies of oncogene-addicted CRCs, and determine how distinct tumour metabolic profiles can confer resistance or predict sensitivity to standard-of-care or novel targeted therapies. Moreover, as a key contributor to the CRUK Grand Challenge SpecifiCancer consortium, we are employing transcriptional, epigenetic, and proteomic approaches to understand why there are tissue- and cell type-specific differences in the response to oncogenic mutations, with the aim of developing methods to suppress the impact of these mutations in cancer.
In addition, we are partnering with a number of leading industry innovator to accelerate the path from bench to bedside. For example, in partnership with Novartis, we are working towards the development of novel KRAS inhibitors, to address a pressing clinical need in colorectal cancer.
Read about his 2009 Nature paper on the CRUK science blog and listen to him talking about bowel cancer stem cells.
See a Google Hangout on the subject of red meat and cancer featuring Owen Sansom and Kathryn Bradbury from the University of Oxford: https://www.youtube.com/watch?v=jS1QW74wJRw
Jackstadt R, van Hooff SR, Leach JD, Cortes-Lavaud X, Lohuis JO, Ridgway RA, Wouters VM, Roper J, Kendall TJ, Roxburgh CS, Horgan PG, Nixon C, Nourse C, Gunzer M, Clark W, Hedley A, Yilmaz OH, Rashid M, Bailey P, Biankin AV, Campbell AD, Adams DJ, Barry ST, Steele CW, Medema JP, Sansom OJ. Epithelial NOTCH Signaling Rewires the Tumor Microenvironment of Colorectal Cancer to Drive Poor-Prognosis Subtypes and Metastasis. Cancer cell. 2019; 36: 319-336.e317.
Johansson J, Naszai M, Hodder MC, Pickering KA, Miller BW, Ridgway RA, Yu Y, Peschard P, Brachmann S, Campbell AD, Cordero JB, Sansom OJ. RAL GTPases Drive Intestinal Stem Cell Function and Regeneration through Internalization of WNT Signalosomes. Cell Stem Cell. 2019; 24: 592-607.e7.
Faller WJ, Jackson TJ, Knight JR, Ridgway RA, Jamieson T, Karim SA, Jones C, Radulescu S, Huels DJ, Myant KB, Dudek KM, Casey HA, Scopelliti A, Cordero JB, Vidal M, Pende M, Ryazanov AG, Sonenberg N, Meyuhas O, Hall MN, Bushell M, Willis AE, Sansom OJ. mTORC1-mediated translational elongation limits intestinal tumour initiation and growth. Nature. 2014; 517: 497–500
Myant KB, Cammareri P, McGhee EJ, Ridgway RA, Huels DJ, Cordero JB, Schwitalla S, Kalna G, Ogg EL, Athineos D, Timpson P, Vidal M, Murray GI, Greten FR, Anderson KI, Sansom OJ. ROS production and NF-κB activation triggered by RAC1 facilitate WNT-driven intestinal stem cell proliferation and colorectal cancer initiation. Cell Stem Cell. 2013; 12: 761-73
Ashton GH, Morton JP, Myant K, Phesse TJ, Ridgway RA, Marsh V, Wilkins JA, Athineos D, Muncan V, Kemp R, Neufeld K, Clevers H, Brunton V, Winton DJ, Wang X, Sears RC, Clarke AR, Frame MC, Sansom OJ. Focal adhesion kinase is required for intestinal regeneration and tumorigenesis downstream of Wnt/c-Myc signaling. Dev Cell. 2010; 19: 259-69
Morton JP, Timpson P, Karim SA, Ridgway RA, Athineos D, Doyle B, Jamieson NB, Oien KA, Lowy AM, Brunton VG, Frame MC, Evans TR, Sansom OJ. Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer. Proc Natl Acad Sci USA. 2010; 107: 246-51
Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, Danenberg E, Clarke AR, Sansom OJ, Clevers H. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature. 2009 457: 608-11
Sansom OJ, Meniel VS, Muncan V, Phesse TJ, Wilkins JA, Reed KR, Vass JK, Athineos DA, Clevers H, Clarke AR. c-Myc deletion rescues Apc deficiency in the small intestine. Nature. 2007; 446: 676-9
Sansom OJ, Reed KR, Hayes AJ, Ireland H, Brinkmann H, Newton IP, Batlle E, Simon-Assmann P, Clevers H, Nathke IS, Clarke AR, Winton DJ. Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration. Genes Dev. 2004; 18: 1385-90
2002: PhD, University of Edinburgh, Supervisors Alan Clarke and Andrew Wylie
1997: MRes, Biology, University of Manchester
1996: BSc, Genetics (First Class Honours), University of Nottingham
2017-present: Director, CRUK Scotland Institute, Glasgow
2011-2017 Deputy Director, CRUK Beatson Institute, Glasgow
2005-present: Group Leader, CRUK Scotland Institute, Glasgow
2000-2005: Postdoctoral Fellow with Alan Clarke, University of Cardiff
NC3Rs Student Panel
CRUK Programme Grants interviewer
CRUK Drug Discovery Panel
North West Cancer Research Panel
CRUK Pancreatic Cancer Strategy Panel
Advisory Board, MRC Toxicology Unit, Leicester
Advisory Board, Center for Personalized Cancer Therapeutics, Mount Sinai
Advisory Board, Centre of Excellence in Translational Cancer Biology, Academy of Finland
Editorial Board, Disease Models and Mechanisms
Organising Committee, NCRI Cancer Conference, Liverpool
Fellow of the Academy of Medical Sciences, 2017
CRUK Future Leaders in Cancer Research Prize, 2012
Fellow of the Royal Society of Edinburgh, 2012
BACR/AstraZeneca Young Scientist Frank Rose Award, 2007
Domingo E, Kelly C, Hay J, Sansom O, Maka N, Oien K, Iveson T, Saunders M, Kerr R, Tomlinson I, Edwards J, Harkin A, Nowak M, Koelzer V, Easton A, Boukovinas I, Moustou E, Messaritakis I, Chondrozoumaki M, Karagianni M, Pagès F, Arnoux F, Lautard C, Lovera Y, Boquet I, Catteau A, Galon J, Souglakos I, Church DN. Prognostic and Predictive Value of Immunoscore in Stage III Colorectal Cancer: Pooled Analysis of Cases From the SCOT and IDEA-HORG Studies. J Clin Oncol. 2024:Jco2301648.
Fetit R, McLaren A, White M, Mills ML, Falconer J, Cortes-Lavaud X, Gilroy K, Lannagan TR, Ridgway RA, Nixon C, Naiker V, Njunge R, Clarke CJ, Whyte D, Kirschner K, Jackstadt R, Norman JC, Carlin LM, Campbell AD, Sansom OJ, Steele CW. Characterising neutrophil subtypes in cancer using scRNA sequencing demonstrates the importance of IL-1β/CXCR2 axis in generation of metastasis specific neutrophils. Cancer Res Commun. 2024.
Ford CA, Koludrovic D, Centeno PP, Foth M, Tsonou E, Vlahov N, Sphyris N, Gilroy K, Bull C, Nixon C, Serrels B, Munro AF, Dawson JC, Carragher NO, Pavet V, Hornigold DC, Dunne PD, Downward J, Welch HCE, Barry ST, Sansom OJ, Campbell AD. A targetable PREX2/RAC1/PI3Kβ signalling axis confers resistance to clinically relevant therapeutic approaches in melanoma. bioRxiv. 2024:2024.2002.2026.580534.
Frei AL, McGuigan A, Sinha R, Jabbar F, Gneo L, Tomasevic T, Harkin A, Iveson T, Saunders MP, Oien KA, Maka N, Pezzella F, Campo L, Browne M, Glaire M, Kildal W, Danielsen HE, Hay J, Edwards J, Sansom O, Kelly C, Tomlinson I, Kerr R, Kerr D, Domingo E, Church DN, Koelzer VH. Multiplex analysis of intratumoural immune infiltrate and prognosis in patients with stage II-III colorectal cancer from the SCOT and QUASAR 2 trials: a retrospective analysis. Lancet Oncol. 2024;25(2):198-211.
Harryvan T, Abudukelimu S, Stouten I, van der Wel E, Janson S, Lenos K, Lannagan T, White M, Sansom O, Verdegaal E, Hawinkels L. TGFβ signaling in cancer-associated fibroblasts drives a hepatic gp130-dependent pro-metastatic inflammatory program in CMS4 colorectal cancer subtype. bioRxiv. 2024:2024.2006.2025.600311.
Loi P, Schade AE, Rodriguez CL, Krishnan A, Perurena N, Nguyen VTM, Xu Y, Watanabe M, Davis RA, Gardner A, Pilla NF, Mattioli K, Popow O, Gunduz N, Lannagan TRM, Fitzgerald S, Sicinska ET, Lin JR, Tan W, Brais LK, Haigis KM, Giannakis M, Ng K, Santagata S, Helin K, Sansom OJ, Cichowski K. Epigenetic and oncogenic inhibitors cooperatively drive differentiation and kill KRAS-mutant colorectal cancers. Cancer Discov. 2024.
Lu Y, Travnickova J, Badonyi M, Rambow F, Coates A, Khan Z, Marques J, Murphy LC, Garcia-Martinez P, Marais R, Louphrasitthiphol P, Chan AHY, Schofield CJ, von Kriegsheim A, Marsh JA, Pavet V, Sansom OJ, Illingworth RS, Patton EE. ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma. Cell Rep. 2024;43(7):114406.
Malla SB, Byrne RM, Lafarge MW, Corry SM, Fisher NC, Tsantoulis PK, Mills ML, Ridgway RA, Lannagan TRM, Najumudeen AK, Gilroy KL, Amirkhah R, Maguire SL, Mulholland EJ, Belnoue-Davis HL, Grassi E, Viviani M, Rogan E, Redmond KL, Sakhnevych S, McCooey AJ, Bull C, Hoey E, Sinevici N, Hall H, Ahmaderaghi B, Domingo E, Blake A, Richman SD, Isella C, Miller C, Bertotti A, Trusolino L, Loughrey MB, Kerr EM, Tejpar S, Maughan TS, Lawler M, Campbell AD, Leedham SJ, Koelzer VH, Sansom OJ, Dunne PD. Pathway level subtyping identifies a slow-cycling biological phenotype associated with poor clinical outcomes in colorectal cancer. Nature Genetics. 2024.
Mulholland E, Belnoue-Davis H, Valbuena G, Gunduz N, Ligezal A, Biswasl S, Vasquez EG, Omwengal S, Nasreddinl N, Hodder M, Wang L, Irshad S, Ng A, Jennings L, Midwood K, Dedi N, Ridgeway R, Phesse T, East J, Tomlinson I, Davies G, Sansom O, Leedham S. GREMLIN1 disrupts intestinal epithelial-mesenchymal crosstalk to induce a wnt-dependent ectopic stem cell niche via stromal remodelling. bioRxiv. 2024:2024.2004.2028.591245.
Najumudeen AK, Fey SK, Millett LM, Ford CA, Gilroy K, Gunduz N, Ridgway RA, Anderson E, Strathdee D, Clark W, Nixon C, Morton JP, Campbell AD, Sansom OJ. KRAS allelic imbalance drives tumour initiation yet suppresses metastasis in colorectal cancer in vivo. Nat Commun. 2024;15(1):100.
Pennel KAF, Hatthakarnkul P, Wood CS, Lian GY, Al-Badran SSF, Quinn JA, Legrini A, Inthagard J, Alexander PG, van Wyk H, Kurniawan A, Hashmi U, Gillespie MA, Mills M, Ammar A, Hay J, Andersen D, Nixon C, Rebus S, Chang DK, Kelly C, Harkin A, Graham J, Church D, Tomlinson I, Saunders M, Iveson T, Lannagan TRM, Jackstadt R, Maka N, Horgan PG, Roxburgh CSD, Sansom OJ, McMillan DC, Steele CW, Jamieson NB, Park JH, Roseweir AK, Edwards J. JAK/STAT3 represents a therapeutic target for colorectal cancer patients with stromal-rich tumors. J Exp Clin Cancer Res. 2024;43(1):64.
Pereira BA, Ritchie S, Chambers CR, Gordon KA, Magenau A, Murphy KJ, Nobis M, Tyma VM, Liew YF, Lucas MC, Naeini MM, Barkauskas DS, Chacon-Fajardo D, Howell AE, Parker AL, Warren SC, Reed DA, Lee V, Metcalf XL, Lee YK, O'Regan LP, Zhu J, Trpceski M, Fontaine ARM, Stoehr J, Rouet R, Lin X, Chitty JL, Porazinski S, Wu SZ, Filipe EC, Cadell AL, Holliday H, Yang J, Papanicolaou M, Lyons RJ, Zaratzian A, Tayao M, Da Silva A, Vennin C, Yin J, Dew AB, McMillan PJ, Goldstein LD, Deveson IW, Croucher DR, Samuel MS, Sim HW, Batten M, Chantrill L, Grimmond SM, Gill AJ, Samra J, Jeffry Evans TR, Sasaki T, Phan TG, Swarbrick A, Sansom OJ, Morton JP, Pajic M, Parker BL, Herrmann D, Cox TR, Timpson P. Temporally resolved proteomics identifies nidogen-2 as a cotarget in pancreatic cancer that modulates fibrosis and therapy response. Sci Adv. 2024;10(27):eadl1197.
Salvador-Barbero B, Alatsatianos M, Morton JP, Sansom OJ, Hogan C. Oncogenic KRAS cells use Wnt signalling and cell dormancy to override homeostatic cell elimination mechanisms in adult pancreas. bioRxiv. 2024:2024.2002.2013.579930.
Whyte D, Voorde JV, Sumpton D, Dhayade S, Dornier E, Moore M, Novo D, Peters J, Wiesheu R, Mackey JBG, McFarlane AJ, Fercoq F, Fisher S, Caballero CD, Gilroy K, Redmond KL, Mitchell LE, Anderson E, Thomson G, Dzierozynski LN, Saab JJA, Lewis CA, Muir A, Halbrook CJ, Strathdee D, Jackstadt R, Nixon C, Dunne P, Steele CW, Carlin LM, Macpherson IR, Roberts EW, Coffelt SB, Blyth K, Sansom OJ, Norman JC, Clarke CJ. Uridine Phosphorylase-1 supports metastasis of mammary cancer by altering immune and extracellular matrix landscapes of the lung. bioRxiv. 2024:2024.2007.2002.601676.
Tesson M, Stevenson K, Karim SA, Nixon C, Chalmers AJ, Sansom OJ, O'Neil E, Jones K, Morton JP. Targeted irradiation in an autochthonous mouse model of pancreatic cancer. Dis Model Mech. 2024.
Amirkhah R, Gilroy K, Malla SB, Lannagan TRM, Byrne RM, Fisher NC, Corry SM, Mohamed N-E, Naderi-Meshkin H, Mills ML, Campbell AD, Ridgway RA, Ahmaderaghi B, Murray R, Llergo AB, Sanz-Pamplona R, Villanueva A, Batlle E, Salazar R, Lawler M, Sansom OJ, Dunne PD. MmCMS: mouse models’ consensus molecular subtypes of colorectal cancer. British Journal of Cancer. 2023;128: 1333–1343
Bailey P, Ridgway RA, Cammareri P, Treanor-Taylor M, Bailey UM, Schoenherr C, Bone M, Schreyer D, Purdie K, Thomson J, Rickaby W, Jackstadt R, Campbell AD, Dimonitsas E, Stratigos AJ, Arron ST, Wang J, Blyth K, Proby CM, Harwood CA, Sansom OJ, Leigh IM, Inman GJ. Driver gene combinations dictate cutaneous squamous cell carcinoma disease continuum progression. Nat Commun. 2023;14:5211.
Chen F, Gurler SB, Novo D, Selli C, Alferez DG, Eroglu S, Pavlou K, Zhang J, Sims AH, Humphreys NE, Adamson A, Campbell A, Sansom OJ, Tournier C, Clarke RB, Brennan K, Streuli CH, Ucar A. RAC1B function is essential for breast cancer stem cell maintenance and chemoresistance of breast tumor cells. Oncogene. 2023; 42: 679–692
Conway JRW, Warren SC, Lee YK, McCulloch AT, Magenau A, Lee V, Metcalf XL, Stoehr J, Haigh K, Abdulkhalek L, Guaman CS, Reed DA, Murphy KJ, Pereira BA, Mélénec P, Chambers C, Latham SL, Lenthall H, Deenick EK, Ma Y, Phan T, Lim E, Joshua AM, Walters S, Grey ST, Shi YC, Zhang L, Herzog H, Croucher DR, Philp A, Scheele C, Herrmann D, Sansom OJ, Morton JP, Papa A, Haigh JJ, Nobis M, Timpson P. Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse. Sci Adv. 2023;9:eadf9063.
Fetit R, White M, Mills ML, Cortes-Lavaud X, McLaren A, Falconer J, Gilroy K, Nixon C, Kirschner K, Jackstadt R, Campbell AD, Sansom OJ, Steele CW. Characterising neutrophil subtypes in cancer using human and murine single-cell RNA sequencing datasets. bioRxiv. 2023;Volume:2023.2007.2013.548820.
Fey SK, Najumudeen AK, Ford C, Gilroy K, Upstill-Goddard R, Chang DK, Clark W, Nixon C, Barry ST, Morton JP, Campbell AD, Sansom OJ. Kras loss of heterozygosity promotes MAPK dependent pancreatic ductal adenocarcinoma and induces therapeutic sensitivity. bioRxiv. 2023:2023.2008.2029.552598.
Frei AL, McGuigan A, Sinha RR, Glaire MA, Jabbar F, Gneo L, Tomasevic T, Harkin A, Iveson TJ, Saunders M, Oein K, Maka N, Pezella F, Campo L, Hay J, Edwards J, Sansom OJ, Kelly C, Tomlinson I, Kildal W, Kerr RS, Kerr DJ, Danielsen HE, Domingo E, Church DN, Koelzer VH.Accounting for intensity variation in image analysis of large-scale multiplexed clinical trial datasets. J Pathol Clin Res. 2023.
Holt AK, Najumudeen AK, Collard TJ, Li H, Millett LM, Hoskin AJ, Legge DN, Mortensson EMH, Flanagan DJ, Jones N, Kollareddy M, Timms P, Hitchings MD, Cronin J, Sansom OJ, Williams AC, Vincent EE. Aspirin reprogrammes colorectal cancer cell metabolism and sensitises to glutaminase inhibition. Cancer Metab. 2023;11(1):18.
Lu Y, Travnickova J, Badonyi M, Rambow F, Coates A, Khan Z, Marques J, Murphy L, Garcia-Martinez P, Marais R, Louphrasitthiphol P, Kriegsheim AV, Marsh JA, Pavet V, Sansom OJ, Illingworth R, Patton EE. ALDH1A3-acetaldehyde re-wires neural crest stem cell and high metabolism states to potentiate melanoma heterogeneity. bioRxiv. 2023:2023.2010.2028.564337.
Malik N, Hay J, Almuhanna HNB, Dunn KM, Lees J, Cassels J, Li J, Nakagawa R, Sansom OJ, Michie AM. mTORC1-selective activation of translation elongation promotes disease progression in chronic lymphocytic leukemia. Leukemia. 2023.
May S, Müller M, Livingstone CR, Skalka GL, Walsh PJ, Nixon C, Hedley A, Shaw R, Clark W, Voorde JV, Officer-Jones L, Ballantyne F, Powley IR, Drake TM, Kiourtis C, Keith A, Rocha AS, Tardito S, Sumpton D, Le Quesne J, Bushell M, Sansom OJ, Bird TG. Absent expansion of AXIN2+ hepatocytes and altered physiology in Axin2CreERT2 mice challenges the role of pericentral hepatocytes in homeostatic liver regeneration. J Hepatol. 2023; 78:1028-1036
Moore M, Pardo L, Mitchell L, Schmidt T, May S, Mueller M, Strathdee D, Bryson S, Hodge K, Lilla S, Zanivan S, Waldron J, McGarry L, Peter-Durairaj R, Kanellos G, Nixon C, Ballantyne F, LeQuesne J, Sansom OJ, Bird T, Bushell M, Norman JC. The eIF4A2 negative regulator of mRNA translation promotes extracellular matrix deposition to accelerate hepatocellular carcinoma initiation. bioRxiv. 2023;Volume:2023.2008.2016.553544.
Mzoughi S, Schwarz M, Wang X, Demircioglu D, Ulukaya G, Mohammed K, Tullio FD, Company C, Dramaretska Y, Leushacke M, Giotti B, Lannagan T, Lozano-Ojalvo D, Hasson D, Tsankov A, Sansom OJ, Marine J-C, Barker N, Gargiulo G, Guccione E. A Mutation-driven oncofetal regression fuels phenotypic plasticity in colorectal cancer. bioRxiv. 2023:2023.2012.2010.570854.
Perurena N, Lock R, Davis RA, Raghavan S, Pilla NF, Ng R, Loi P, Guild CJ, Miller AL, Sicinska E, Cleary JM, Rubinson DA, Wolpin BM, Gray NS, Santagata S, Hahn WC, Morton JP, Sansom OJ, Aguirre AJ, Cichowski K. USP9X mediates an acute adaptive response to MAPK suppression in pancreatic cancer but creates multiple actionable therapeutic vulnerabilities. Cell Rep Med. 2023;4:101007
Suzuki T, Kilbey A, Casa Rodriguez N, Lawlor A, Georgakopoulou A, Hayman H, Yin Swe KL, Nordin A, Cantù C, Vantourout P, Ridgway RA, Byrne RM, Chen L, Verzi MP, Gay DM, Gil Vazquez E, Belnoue-Davis HL, Gilroy K, Kostner AH, Kersten C, Thuwajit C, Andersen DK, Wiesheu R, Jandke A, Blyth K, Roseweir AK, Leedham SJ, Dunne PD, Edwards J, Hayday A, Sansom OJ, Coffelt SB. β-catenin drives butyrophilin-like molecule loss and γδ T-cell exclusion in colon cancer. Cancer Immunology Research. 2023;11:1137–1155
Vande Voorde J, Steven RT, Najumudeen AK, Ford CA, Dexter A, Gonzalez-Fernandez A, Nikula CJ, Xiang Y, Ford L, Maneta Stavrakaki S, Gilroy K, Zeiger LB, Pennel K, Hatthakarnkul P, Elia EA, Nasif A, Murta T, Manoli E, Mason S, Gillespie M, Lannagan TRM, Vlahov N, Ridgway RA, Nixon C, Raven A, Mills M, Athineos D, Kanellos G, Nourse C, Gay DM, Hughes M, Burton A, Yan B, Sellers K, Wu V, De Ridder K, Shokry E, Huerta Uribe A, Clark W, Clark G, Kirschner K, Thienpont B, Li VSW, Maddocks ODK, Barry ST, Goodwin RJA, Kinross J, Edwards J, Yuneva MO, Sumpton D, Takats Z, Campbell AD, Bunch J, Sansom OJ. Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target. Nature Metabolism. 2023;10.1038/s42255-023-00857-0.
van Driel MS, Linssen JDG, Flanagan DJ, Vlahov N, Nijman LE, de Groot NE, Elbers CC, Koster J, Sansom OJ, Vermeulen L, van Neerven SM. Caffeine limits expansion of Apc-deficient clones in the intestine by NOTUM inhibition. Cell Mol Gastroenterol Hepatol. 2023;10.1016/j.jcmgh.2023.06.008.
Villar VH, Allega MF, Deshmukh R, Ackermann T, Nakasone MA, Vande Voorde J, Drake TM, Oetjen J, Bloom A, Nixon C, Müller M, May S, Tan EH, Vereecke L, Jans M, Blancke G, Murphy DJ, Huang DT, Lewis DY, Bird TG, Sansom OJ, Blyth K, Sumpton D, Tardito S. Hepatic glutamine synthetase controls N5-methylglutamine in homeostasis and cancer. Nature Chemical Biology. 2023;19:292-300.
Waldron JA, Kanellos G, Smith RCL, Knight JRP, Munro J, Alexandrou C, Vlahov N, Pardo-Fernandez L, Moore M, Gillen SL, Strathdee D, Stevenson D, Warrander FC, Gilroy K, Nixon C, Cadden B, Powley I, Officer-Jones L, Ballantyne F, Hay J, Pennel K, Edwards J, Campbell AD, Ridgway RA, Coffelt SB, Norman J, Quesne JL, Bushell M, Sansom OJ. eIF4A1 is essential for reprogramming the translational landscape of Wnt-driven colorectal cancers. bioRxiv. 2023:2023.2011.2010.566546.
Wood CS, Pennel KAF, Leslie H, Legrini A, Cameron AJ, Melissourgou-Syka L, Quinn JA, van Wyk HC, Hay J, Roseweir AK, Nixon C, Roxburgh CSD, McMillan DC, Biankin AV, Sansom OJ, Horgan PG, Edwards J, Steele CW, Jamieson NB. Spatially Resolved Transcriptomics Deconvolutes Prognostic Histological Subgroups in Patients with Colorectal Cancer and Synchronous Liver Metastases. Cancer Res. 2023;83:1329-1344.
Ahmaderaghi B, Amirkhah R, Jackson J, Lannagan TRM, Gilroy K, Malla SB, Redmond KL, Quinn G, McDade S, Consortium A, Maughan T, Leedham S, Campbell AS, Sansom OJ, Lawler M, Dunne PD. The molecular subtyping resource (MouSR): a user-friendly tool for rapid biological discovery from transcriptional data. Dis Model Mech. 2022;15: dmm049257.
Ali A, Jamieson NB, Khan IN, Chang D, Giovannetti E, Funel N, Frampton AE, Morton J, Sansom O, Evans TRJ, Duthie F, McKay CJ, Samra J, Gill AJ, Biankin A, Oien KA. Prognostic implications of microRNA-21 overexpression in pancreatic ductal adenocarcinoma: an international multicenter study of 686 patients. Am J Cancer Res. 2022;12:5668-5683.
Azkanaz M, Corominas-Murtra B, Ellenbroek SIJ, Bruens L, Webb AT, Laskaris D, Oost KC, Lafirenze SJA, Annusver K, Messal HA, Iqbal S, Flanagan DJ, Huels DJ, Rojas-Rodríguez F, Vizoso M, Kasper M, Sansom OJ, Snippert HJ, Liberali P, Simons BD, Katajisto P, Hannezo E, van Rheenen J. Retrograde movements determine effective stem cell numbers in the intestine. Nature. 2022;607:548-554.
Cook DR, Kang M, Martin TD, Galanko JA, Loeza GH, Trembath DG, Justilien V, Pickering KA, Vincent DF, Jarosch A, Jurmeister P, Waters AM, Hibshman PS, Campbell AD, Ford CA, Keku TO, Yeh JJ, Lee MS, Cox AD, Fields AP, Sandler RS, Sansom OJ, Sers C, Schaefer A, Der CJ. Aberrant expression and subcellular localization of ECT2 drives colorectal cancer progression and growth. Cancer Res. 2022; 82:90-104
Corry SM, McCorry AM, Lannagan TR, Leonard NA, Fisher NC, Byrne RM, Tsantoulis P, Cortes-Lavaud X, Amirkhah R, Redmond KL, McCooey AJ, Malla SB, Rogan E, Sakhnevych S, Gillespie MA, White M, Richman SD, Jackstadt RF, Campbell AD, Maguire S, McDade SS, Longley 1137–1155DB, Loughrey MB, Coleman HG, Kerr EM, Tejpar S, Maughan T, Leedham SJ, Small DM, Ryan AE, Sansom OJ, Lawler M, Dunne PD. Activation of innate-adaptive immune machinery by poly(I:C) exposes a therapeutic vulnerability to prevent relapse in stroma-rich colon cancer. Gut. 2022;71:2502-2517
Fisher NC, Byrne RM, Leslie H, Wood C, Legrini A, Cameron AJ, Ahmaderaghi B, Corry SM, Malla SB, Amirkhah R, McCooey AJ, Rogan E, Redmond KL, Sakhnevych S, Domingo E, Jackson J, Loughrey MB, Leedham S, Maughan T, Lawler M, Sansom OJ, Lamrock F, Koelzer VH, Jamieson NB, Dunne PD. Biological Misinterpretation of Transcriptional Signatures in Tumor Samples can Unknowingly Undermine Mechanistic Understanding and Faithful Alignment with Preclinical Data. Clinical Cancer Research. 2022;10.1158/1078-0432.Ccr-22-1102:OF1-OF14.
Flanagan DJ, Amirkhah R, Vincent DF, Gundaz N, Gentaz P, Cammareri P, McCooey AJ, McCorry AMB, Fisher NC, Davis HL, Ridgway RA, Lohuis J, Leach JDG, Jackstadt R, Gilroy K, Mariella E, Nixon C, Clark W, Hedley A, Markert EK, Strathdee D, Bartholin L, Redmond KL, Kerr EM, Longley DB, Ginty F, Cho S, Coleman HG, Loughrey MB, Bardelli A, Maughan TS, Campbell AD, Lawler M, Leedham SJ, Barry ST, Inman GJ, van Rheenen J, Dunne PD, Sansom OJ. Epithelial TGFβ engages growth-factor signalling to circumvent apoptosis and drive intestinal tumourigenesis with aggressive features. Nat Commun. 2022;13:7551.
Freckmann EC, Sandilands E, Cumming E, Neilson M, Román-Fernández A, Nikolatou K, Nacke M, Lannagan TRM, Hedley A, Strachan D, Salji M, Morton JP, McGarry L, Leung HY, Sansom OJ, Miller CJ, Bryant DM. Traject3d allows label-free identification of distinct co-occurring phenotypes within 3D culture by live imaging. Nat Commun. 2022;13:5317.
Gil Vasquez E, Nasreddin N, Valbuena GN, Mulholland EJ, Belnoue-Davis HL, Eggington H, Schenck RO, Wouters VM, Wirapati P, Gilroy K, Lannagan TRM, Flanagan DJ, Najumudeen AK, Omwenga S, McCorry AMB, Easton A, Koelzer VH, East JE, Morton D, Trusolino L, Maughan T, Campbell AD, Loughrey MB, Dunne PD, Tsantoulis P, Huels DJ, Tejpar S, Sansom O, Leedham SJ. Molecular phenotyping of colorectal neoplasia shows dynamic and adaptive cancer stem cell population admixture. bioRxiv. 2022;Volume:2022.2006.2011.495729.
Hedayioglu F, Mead EJ, O'Connor PBF, Skiotys M, Sansom OJ, Mallucci GR, Willis AE, Baranov PV, Smales CM, von der Haar T. Evaluating data integrity in ribosome footprinting datasets through modelled polysome profiles. Nucleic Acids Res. 2022;50:e112
Kidger AM, Saville MK, Rushworth LK, Davidson J, Stellzig J, Ono M, Kuebelsbeck LA, Janssen KP, Holzmann B, Morton JP, Sansom OJ, Caunt CJ, Keyse SM. Suppression of mutant Kirsten-RAS (KRAS(G12D))-driven pancreatic carcinogenesis by dual-specificity MAP kinase phosphatases 5 and 6. Oncogene. 2022;41:2811–2823
Knight JRP, Proud CG, Mallucci G, Haar TV, Smales CM, Willis AE, Sansom OJ. eEF2K activity is required for the phenotypes of the Rpl24(Bst) mouse. J Invest Dermatol. 2022;142:3346-3348.e1
Leslie J, Mackey JBG, Jamieson T, Ramon-Gil E, Drake TM, Fercoq F, Clark W, Gilroy K, Hedley A, Nixon C, Luli S, Laszczewska M, Pinyol R, Esteban-Fabró R, Willoughby CE, Haber PK, Andreu-Oller C, Rahbari M, Fan C, Pfister D, Raman S, Wilson N, Müller M, Collins A, Geh D, Fuller A, McDonald D, Hulme G, Filby A, Cortes-Lavaud X, Mohamed N-E, Ford CA, Raffo Iraolagoitia XL, McFarlane AJ, McCain MV, Ridgway RA, Roberts EW, Barry ST, Graham GJ, Heikenwälder M, Reeves HL, Llovet JM, Carlin LM, Bird TG, Sansom OJ, Mann DA. CXCR2 inhibition enables NASH-HCC immunotherapy. Gut. 2022;
Malik N, Hay J, Dunn KM, Nakagawa R, Sansom OJ, Michie AM. mTORC1 activity is essential for disease progression in chronic lymphocytic leukemia. bioRxiv; 10.1101/2022.04.19.4887782022:2022.2004.2019.488778.
May S, Greenow KR, Higgins AT, Derrick AV, Taylor E, Pan P, Konstantinou M, Nixon C, Wooley TE, Sansom OJ, Wang LS, Parry L. Modification of Diet to Reduce the Stemness and Tumorigenicity of Murine and Human Intestinal Cells. Mol Nutr Food Res. 2022;66:2200234
Parker C, Chambers AC, Flanagan DJ, Ho JWY, Collard TJ, Ngo G, Baird DM, Timms P, Morgan RG, Sansom OJ, Williams AC. BCL-3 loss sensitises colorectal cancer cells to DNA damage by targeting homologous recombination. DNA Repair (Amst). 2022;115:103331.
Patel R, Ford CA, Rodgers L, Rushworth LK, Fleming J, Mui E, Zhang T, Watson D, Lynch V, Mackay G, Sumpton D, Sansom OJ, Vande Voorde J, Leung HY. Cyclocreatine suppresses creatine metabolism and impairs prostate cancer progression. Cancer Res. 2022;82: 2565–2575
Ramadan R, Wouters VM, van Neerven SM, de Groot NE, Martins GT, Muncan V, Franklin OD, Battle M, Carlson KS, Leach J, Sansom OJ, Boulard O, Chamaillard M, Vermeulen L, Medema JP, Huels DJ. The extracellular matrix controls stem cell specification and crypt morphology in the developing and adult mouse gut. Biol Open. 2022;11:bio059544
Strittmatter N, Richards FM, Race AM, Ling S, Sutton D, Nilsson A, Wallez Y, Barnes J, Maglennon G, Gopinathan A, Brais R, Wong E, Serra MP, Atkinson J, Smith A, Wilson J, Hamm G, Johnson TI, Dunlop CR, Kaistha BP, Bunch J, Sansom OJ, Takats Z, Andrén PE, Lau A, Barry ST, Goodwin RJA, Jodrell DI. Method To Visualize the Intratumor Distribution and Impact of Gemcitabine in Pancreatic Ductal Adenocarcinoma by Multimodal Imaging. Anal Chem. 2022;94:1795–1803
Vasquez EG, Nasreddin N, Valbuena GN, Mulholland EJ, Belnoue-Davis HL, Eggington HR, Schenck RO, Wouters VM, Wirapati P, Gilroy K, Lannagan TRM, Flanagan DJ, Najumudeen AK, Omwenga S, McCorry AMB, Easton A, Koelzer VH, East JE, Morton D, Trusolino L, Maughan T, Campbell AD, Loughrey MB, Dunne PD, Tsantoulis P, Huels DJ, Tejpar S, Sansom OJ, Leedham SJ. Dynamic and adaptive cancer stem cell population admixture in colorectal neoplasia. Cell Stem Cell. 2022;29:1213-1228.e1218.
Walter RJ, Sonnentag SJ, Munoz-Sagredo L, Merkel M, Richert L, Bunert F, Heneka YM, Loustau T, Hodder M, Ridgway RA, Sansom OJ, Mely Y, Rothbauer U, Schmitt M, Orian-Rousseau V. Wnt signaling is boosted during intestinal regeneration by a CD44-positive feedback loop. Cell Death Dis. 2022;13:168.
Bristow RG, Engel J, Jayasinghe I, Kampmann M, James Sansom O, Bryant DM. Conversations with LGBT+ scientists about visibility, leadership and climbing the career ladder. Journal of Cell Science. 2022;135.
Flanagan DJ, Woodcock SA, Phillips C, Eagle C, Sansom OJ. Targeting ligand-dependent wnt pathway dysregulation in gastrointestinal cancers through porcupine inhibition. Pharmacol Ther. 2022:108179.
Sansom O. A new network for the synergistic translation of mouse research. Dis Model Mech. 2022;15:dmm049865
Alexander PG, Roseweir AK, Pennel KAF, van Wyk HC, Powell A, McMillan DC, Horgan PG, Kelly C, Hay J, Sansom O, Harkin A, Roxburgh CSD, Graham J, Church DN, Tomlinson I, Saunders M, Iveson TJ, Edwards J, Park JH. The Glasgow Microenvironment Score associates with prognosis and adjuvant chemotherapy response in colorectal cancer. Br J Cancer. 2021;124:786-796.
Dreyer SB, Upstill-Goddard R, Paulus-Hock V, Paris C, Lampraki EM, Dray E, Serrels B, Caligiuri G, Rebus S, Plenker D, Galluzzo Z, Brunton H, Cunningham R, Tesson M, Nourse C, Bailey UM, Jones M, Moran-Jones K, Wright DW, Duthie F, Oien K, Evers L, McKay CJ, McGregor GA, Gulati A, Brough R, Bajrami I, Pettitt S, Dziubinski ML, Candido J, Balkwill F, Barry ST, Grützmann R, Rahib L, Johns A, Pajic M, Froeling FEM, Beer P, Musgrove EA, Petersen GM, Ashworth A, Frame MC, Crawford HC, Simeone DM, Lord C, Mukhopadhyay D, Pilarsky C, Tuveson DA, Cooke SL, Jamieson NB, Morton JP, Sansom OJ, Bailey PJ, Biankin AV, Chang DK. Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer. Gastroenterology. 2021;160(1):362-377.e313.
Dunbar K, Valanciute A, Lima ACS, Vinuela PF, Jamieson T, Rajasekaran V, Blackmur J, Ochocka-Fox AM, Guazzelli A, Cammareri P, Arends MJ, Sansom OJ, Myant KB, Farrington SM, Dunlop MG, Din FVN. Aspirin Rescues Wnt-Driven Stem-like Phenotype in Human Intestinal Organoids and Increases the Wnt Antagonist Dickkopf-1. Cell Mol Gastroenterol Hepatol. 2021;11(2):465-489.
Falcomata C, Barthel S, Ulrich A, Diersch S, Veltkamp C, Rad L, Boniolo F, Solar M, Steiger K, Seidler B, Zukowska M, Madej J, Wang M, Ollinger R, Maresch R, Barenboim M, Eser S, Tschurtschenthaler M, Mehrabi A, Roessler S, Goeppert B, Kind A, Schnieke A, Robles MS, Bradley A, Schmid RM, Schmidt-Supprian M, Reichert M, Weichert W, Sansom OJ, Morton JP, Rad R, Schneider G, Saur D. Genetic screens identify a context-specific PI3K/p27Kip1 node driving extrahepatic biliary cancer. Cancer Discov. 2021;11:3158–3177
Flanagan DJ, Pentinmikko N, Luopajärvi K, Willis NJ, Gilroy K, Raven AP, McGarry L, Englund JI, Webb AT, Scharaw S, Nasreddin N, Hodder MC, Ridgway RA, Minnee E, Sphyris N, Gilchrist E, Najumudeen AK, Romagnolo B, Perret C, Williams AC, Clevers H, Nummela P, Lähde M, Alitalo K, Hietakangas V, Hedley A, Clark W, Nixon C, Kirschner K, Jones EY, Ristimäki A, Leedham SJ, Fish PV, Vincent JP, Katajisto P, Sansom OJ. NOTUM from Apc-mutant cells biases clonal competition to initiate cancer. Nature. 2021;594(7863):430-435.
Floerchinger A, Murphy KJ, Latham SL, Warren SC, McCulloch AT, Lee YK, Stoehr J, Mélénec P, Guaman CS, Metcalf XL, Lee V, Zaratzian A, Da Silva A, Tayao M, Rolo S, Phimmachanh M, Sultani G, McDonald L, Mason SM, Ferrari N, Ooms LM, Johnsson AE, Spence HJ, Olson MF, Machesky LM, Sansom OJ, Morton JP, Mitchell CA, Samuel MS, Croucher DR, Welch HCE, Blyth K, Caldon CE, Herrmann D, Anderson KI, Timpson P, Nobis M. Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: Guidance using optical window intravital FRET imaging. Cell Rep. 2021;36(11):109689.
Galbraith LCA, Mui E, Nixon C, Hedley A, Strachan D, MacKay G, Sumpton D, Sansom OJ, Leung HY, Ahmad I. PPAR-gamma induced AKT3 expression increases levels of mitochondrial biogenesis driving prostate cancer. Oncogene. 2021;40:2355-2366.
Grosso S, Marini A, Gyuraszova K, Voorde JV, Sfakianos A, Garland GD, Tenor AR, Mordue R, Chernova T, Morone N, Sereno M, Smith CP, Officer L, Farahmand P, Rooney C, Sumpton D, Das M, Teodósio A, Ficken C, Martin MG, Spriggs RV, Sun XM, Bushell M, Sansom OJ, Murphy D, MacFarlane M, Le Quesne JPC, Willis AE. The pathogenesis of mesothelioma is driven by a dysregulated translatome. Nat Commun. 2021;12:4920.
Gudiño V, Pohl S, Billard CV, Cammareri P, Bolado A, Aitken S, Stevenson D, Hall AE, Agostino M, Cassidy J, Nixon C, von Kriegsheim A, Freile P, Popplewell L, Dickson G, Murphy L, Wheeler A, Dunlop M, Din F, Strathdee D, Sansom OJ, Myant KB. RAC1B modulates intestinal tumourigenesis via modulation of WNT and EGFR signalling pathways. Nat Commun. 2021;12:2335.
Guillermin O, Angelis N, Sidor CM, Ridgway R, Baulies A, Kucharska A, Antas P, Rose MR, Cordero J, Sansom O, Li VSW, Thompson BJ. Wnt and Src signals converge on YAP-TEAD to drive intestinal regeneration. Embo j. 2021:e105770.
Heino S, Fang S, Lähde M, Högström J, Nassiri S, Campbell A, Flanagan D, Raven A, Hodder M, Nasreddin N, Xue HH, Delorenzi M, Leedham S, Petrova TV, Sansom O, Alitalo K. Lef1 restricts ectopic crypt formation and tumor cell growth in intestinal adenomas. Sci Adv. 2021;7(47):eabj0512.
Hill W, Zaragkoulias A, Salvador-Barbero B, Parfitt GJ, Alatsatianos M, Padilha A, Porazinski S, Woolley TE, Morton JP, Sansom OJ, Hogan C. EPHA2-dependent outcompetition of KRASG12D mutant cells by wild-type neighbors in the adult pancreas. Curr Biol. 2021;31:2550-2560.e5
Hutton C, Heider F, Blanco-Gomez A, Banyard A, Kononov A, Zhang X, Karim S, Paulus-Hock V, Watt D, Steele N, Kemp S, Hogg EKJ, Kelly J, Jackstadt RF, Lopes F, Menotti M, Chisholm L, Lamarca A, Valle J, Sansom OJ, Springer C, Malliri A, Marais R, Pasca di Magliano M, Zelenay S, Morton JP, Jørgensen C. Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity. Cancer Cell. 2021; 39: 1227-1244.e20
Knight JRP, Alexandrou C, Skalka GL, Vlahov N, Pennel K, Officer L, Teodosio A, Kanellos G, Gay DM, May-Wilson S, Smith EM, Najumudeen AK, Gilroy K, Ridgway RA, Flanagan DJ, Smith RCL, McDonald L, MacKay C, Cheasty A, McArthur K, Stanway E, Leach JD, Jackstadt R, Waldron JA, Campbell AD, Vlachogiannis G, Valeri N, Haigis KM, Sonenberg N, Proud CG, Jones NP, Swarbrick ME, McKinnon HJ, Faller WJ, Le Quesne J, Edwards J, Willis AE, Bushell M, Sansom OJ. MNK Inhibition Sensitizes KRAS-Mutant Colorectal Cancer to mTORC1 Inhibition by Reducing eIF4E Phosphorylation and c-MYC Expression. Cancer Discov. 2021;11(5):1228-1247.
Knight JR, Vlahov N, Gay DM, Ridgway RA, Faller WJ, Proud C, Mallucci GR, von der Haar T, Smales CM, Willis AE, Sansom OJ. Rpl24(Bst) mutation suppresses colorectal cancer by promoting eEF2 phosphorylation via eEF2K. Elife. 2021;10:e69729
Krotenberg Garcia A, Fumagalli A, Le HQ, Jackstadt R, Lannagan TRM, Sansom OJ, van Rheenen J, Suijkerbuijk SJE. Active elimination of intestinal cells drives oncogenic growth in organoids. Cell Rep. 2021;36:109307.
Lähde M, Heino S, Högström J, Kaijalainen S, Anisimov A, Flanagan D, Kallio P, Leppänen VM, Ristimäki A, Ritvos O, Wu K, Tammela T, Hodder M, Sansom OJ, Alitalo K. Expression of R-Spondin 1 in Apc(Min/+) Mice Suppresses Growth of Intestinal Adenomas by Altering Wnt and Transforming Growth Factor Beta Signaling. Gastroenterology. 2021;160(1):245-259.
Lampis A, Hahne JC, Gasparini P, Cascione L, Hedayat S, Vlachogiannis G, Murgia C, Fontana E, Edwards J, Horgan PG, Terracciano L, Sansom OJ, Martins CD, Kramer-Marek G, Croce CM, Braconi C, Fassan M, Valeri N. MIR21-induced loss of junctional adhesion molecule A promotes activation of oncogenic pathways, progression and metastasis in colorectal cancer. Cell Death Differ. 2021; 28: 2970–2982
Leach JDG, Vlahov N, Tsantoulis P, Ridgway RA, Flanagan DJ, Gilroy K, Sphyris N, Vázquez EG, Vincent DF, Faller WJ, Hodder MC, Raven A, Fey S, Najumudeen AK, Strathdee D, Nixon C, Hughes M, Clark W, Shaw R, van Hooff SR, Huels DJ, Medema JP, Barry ST, Frame MC, Unciti-Broceta A, Leedham SJ, Inman GJ, Jackstadt R, Thompson BJ, Campbell AD, Tejpar S, Sansom OJ. Oncogenic BRAF, unrestrained by TGFβ-receptor signalling, drives right-sided colonic tumorigenesis. Nat Commun. 2021;12:3464.
Mackey JBG, McFarlane AJ, Jamieson T, Jackstadt R, Raffo-Iraolagoitia XL, Secklehner J, Cortes-Lavaud X, Fercoq F, Clarke W, Hedley A, Gilroy K, Lilla S, Vuononvirta J, Graham GJ, De Filippo K, Murphy DJ, Steele CW, Norman JC, Bird TG, Mann DA, Morton JP, Zanivan S, Sansom OJ, Carlin LM. Maturation, developmental site, and pathology dictate murine neutrophil function. bioRxiv. 2021.
Minnis-Lyons SE, Ferreira-González S, Aleksieva N, Man TY, Gadd VL, Williams MJ, Guest RV, Lu WY, Dwyer BJ, Jamieson T, Nixon C, Van Hul N, Lemaigre FP, McCafferty J, Leclercq IA, Sansom OJ, Boulter L, Forbes SJ. Notch-IGF1 signaling during liver regeneration drives biliary epithelial cell expansion and inhibits hepatocyte differentiation. Sci Signal. 2021;14:eaay9185
Murphy KJ, Reed DA, Vennin C, Conway JRW, Nobis M, Yin JX, Chambers CR, Pereira BA, Lee V, Filipe EC, Trpceski M, Ritchie S, Lucas MC, Warren SC, Skhinas JN, Magenau A, Metcalf XL, Stoehr J, Major G, Parkin A, Bidanel R, Lyons RJ, Zaratzian A, Tayao M, Da Silva A, Abdulkhalek L, Gill AJ, Johns AL, Biankin AV, Samra J, Grimmond SM, Chou A, Goetz JG, Samuel MS, Lyons JG, Burgess A, Caldon CE, Horvath LG, Daly RJ, Gadegaard N, Wang Y, Sansom OJ, Morton JP, Cox TR, Pajic M, Herrmann D, Timpson P. Intravital imaging technology guides FAK-mediated priming in pancreatic cancer precision medicine according to Merlin status. Sci Adv. 2021;7:eabh0363.
Murta T, Steven RT, Nikula CJ, Thomas SA, Zeiger LB, Dexter A, Elia EA, Yan B, Campbell AD, Goodwin RJA, Takáts Z, Sansom OJ, Bunch J. Implications of Peak Selection in the Interpretation of Unsupervised Mass Spectrometry Imaging Data Analyses. Anal Chem. 2021; 93: 2309–2316
Najumudeen AK, Ceteci F, Fey SK, Hamm G, Steven RT, Hall H, Nikula CJ, Dexter A, Murta T, Race AM, Sumpton D, Vlahov N, Gay DM, Knight JRP, Jackstadt R, Leach JDG, Ridgway RA, Johnson ER, Nixon C, Hedley A, et al. The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer. Nat Genet. 2021;53:16-26.
Nászai M, Bellec K, Yu Y, Román-Fernández A, Sandilands E, Johansson J, Campbell AD, Norman JC, Sansom OJ, Bryant DM, Cordero JB. RAL GTPases mediate EGFR-driven intestinal stem cell proliferation and tumourigenesis. Elife. 2021;10:e63807
Nielsen SR, Strøbech JE, Horton ER, Jackstadt R, Laitala A, Bravo MC, Maltese G, Jensen ARD, Reuten R, Rafaeva M, Karim SA, Hwang CI, Arnes L, Tuveson DA, Sansom OJ, Morton JP, Erler JT. Suppression of tumor-associated neutrophils by lorlatinib attenuates pancreatic cancer growth and improves treatment with immune checkpoint blockade. Nat Commun. 2021;12(1):3414.
O'Connor MN, Kallenberg DM, Camilli C, Pilotti C, Dritsoula A, Jackstadt R, Bowers CE, Watson HA, Alatsatianos M, Ohme J, Dowsett L, George J, Blackburn JWD, Wang X, Singhal M, Augustin HG, Ager A, Sansom OJ, Moss SE, Greenwood J. LRG1 destabilizes tumor vessels and restricts immunotherapeutic potency. Med (N Y). 2021;2:1231-1252.e1210.
Pickering KA, Gilroy K, Cassidy JW, Fey SK, Najumudeen AK, Zeiger LB, Vincent DF, Gay DM, Johansson J, Fordham RP, Miller B, Clark W, Hedley A, Unal EB, Kiel C, McGhee E, Machesky LM, Nixon C, Johnsson AE, Bain M, et al. A RAC-GEF network critical for early intestinal tumourigenesis. Nat Commun. 2021;12:56.
Race AM, Sutton D, Hamm G, Maglennon G, Morton JP, Strittmatter N, Campbell A, Sansom OJ, Wang Y, Barry ST, Takáts Z, Goodwin RJA, Bunch J. Deep Learning-Based Annotation Transfer between Molecular Imaging Modalities: An Automated Workflow for Multimodal Data Integration. Anal Chem. 2021;93(6):3061-3071.
Ramesh P, Lannagan TRM, Jackstadt R, Atencia Taboada L, Lansu N, Wirapati P, van Hooff SR, Dekker D, Pritchard J, Kirov AB, van Neerven SM, Tejpar S, Kops G, Sansom OJ, Medema JP. BCL-XL is crucial for progression through the adenoma-to-carcinoma sequence of colorectal cancer. Cell Death Differ. 2021;28:3282–3296
Sacchetti A, Teeuwssen M, Verhagen M, Joosten R, Xu T, Stabile R, van der Steen B, Watson MM, Gusinac A, Kim WK, Ubink I, Van de Werken HJ, Fumagalli A, Paauwe M, Van Rheenen J, Sansom OJ, Kranenburg O, Fodde R. Phenotypic plasticity underlies local invasion and distant metastasis in colon cancer. Elife. 2021;10:61461
Sharbeen G, McCarroll JA, Akerman A, Kopecky C, Youkhana J, Kokkinos J, Holst J, Boyer C, Erkan M, Goldstein D, Timpson P, Cox TR, Pereira BA, Chitty JL, Fey SK, Najumudeen AK, Campbell AD, Sansom OJ, Ignacio RMC, Naim S, Liu J, Russia N, Lee J, Chou A, Johns A, Gill AJ, Gonzales-Aloy E, Gebski V, Guan YF, Pajic M, Turner N, Apte MV, Davis TP, Morton JP, Haghighi KS, Kasparian J, McLean BJ, Setargew YFI, Apgi A, Phillips PA. Cancer-associated fibroblasts in pancreatic ductal adenocarcinoma determine response to SLC7A11 inhibition. Cancer Res. 2021; 81:
Swaminathan K, Campbell A, Papalazarou V, Jaber-Hijazi F, Nixon C, McGhee E, Strathdee D, Sansom OJ, Machesky LM. The RAC1 Target NCKAP1 Plays a Crucial Role in the Progression of Braf;Pten-Driven Melanoma in Mice. J Invest Dermatol. 2021;141(3):628-637.e615.
Tajan M, Hennequart M, Cheung EC, Zani F, Hock AK, Legrave N, Maddocks ODK, Ridgway RA, Athineos D, Suárez-Bonnet A, Ludwig RL, Novellasdemunt L, Angelis N, Li VSW, Vlachogiannis G, Valeri N, Mainolfi N, Suri V, Friedman A, Manfredi M, et al. Serine synthesis pathway inhibition cooperates with dietary serine and glycine limitation for cancer therapy. Nat Commun. 2021;12:366.
van der Weyden L, Harle V, Turner G, Offord V, Iyer V, Droop A, Swiatkowska A, Rabbie R, Campbell AD, Sansom OJ, Pardo M, Choudhary JS, Ferreira I, Tullett M, Arends MJ, Speak AO, Adams DJ. CRISPR activation screen in mice identifies novel membrane proteins enhancing pulmonary metastatic colonisation. Commun Biol. 2021;4(1):395.
Gillespie MA, Steele CW, Lannagan TRM, Sansom OJ, Roxburgh CSD. Pre-clinical modelling of rectal cancer to develop novel radiotherapy-based treatment strategies. Oncol Rev. 2021;15:511.
Knight JRP, Sansom OJ. Tuning protein synthesis for cancer therapy. Mol Cell Oncol. 2021;8:1884034.
Lannagan TR, Jackstadt R, Leedham SJ, Sansom OJ. Advances in colon cancer research: in vitro and animal models. Curr Opin Genet Dev. 2021;66:50-56.
Rosenfeldt MT, O'Prey J, Lindsay CR, Nixon C, Roth S, Sansom OJ, Ryan KM. Loss of autophagy affects melanoma development in a manner dependent on PTEN status. Cell Death Differ. 2021;28:1437-1439.
Smith RCL, Kanellos G, Vlahov N, Alexandrou C, Willis AE, Knight JRP, Sansom OJ. Translation initiation in cancer at a glance. J Cell Sci. 2021;134:jcs248476.
Sphyris N, Hodder MC, Sansom OJ. Subversion of Niche-Signalling Pathways in Colorectal Cancer: What Makes and Breaks the Intestinal Stem Cell. Cancers (Basel). 2021;13:1000
Bruens L, Ellenbroek SIJ, Suijkerbuijk SJE, Azkanaz M, Hale AJ, Toonen P, Flanagan DJ, Sansom OJ, Snippert HJ, van Rheenen J. Calorie Restriction Increases the Number of Competing Stem Cells and Decreases Mutation Retention in the Intestine. Cell Rep. 2020;32(3):107937.
Brunton H, Caligiuri G, Cunningham R, Upstill-Goddard R, Bailey UM, Garner IM, Nourse C, Dreyer S, Jones M, Moran-Jones K, Wright DW, Paulus-Hock V, Nixon C, Thomson G, Jamieson NB, McGregor GA, Evers L, McKay CJ, Gulati A, Brough R, Bajrami I, Pettitt SJ, Dziubinski ML, Barry ST, Grützmann R, Brown R, Curry E, Pajic M, Musgrove EA, Petersen GM, Shanks E, Ashworth A, Crawford HC, Simeone DM, Froeling FEM, Lord CJ, Mukhopadhyay D, Pilarsky C, Grimmond SE, Morton JP, Sansom OJ, Chang DK, Bailey PJ, Biankin AV. HNF4A and GATA6 Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer. Cell Rep. 2020;31:107625
Dannhorn A, Kazanc E, Ling S, Nikula C, Karali E, Serra MP, Vorng JL, Inglese P, Maglennon G, Hamm G, Swales J, Strittmatter N, Barry ST, Sansom OJ, Poulogiannis G, Bunch J, Goodwin RJ, Takats Z. Universal Sample Preparation Unlocking Multimodal Molecular Tissue Imaging. Anal Chem. 2020;92(16):11080-11088.
Dreyer SB, Jamieson NB, Morton JP, Sansom OJ, Biankin AV, Chang DK. Pancreatic Cancer: From Genome Discovery to PRECISION-Panc. Clinical oncology (Royal College of Radiologists (Great Britain)). 2020; 32: 5–8
Healy ME, Boege Y, Hodder MC, Böhm F, Malehmir M, Scherr AL, Jetzer J, Chan LK, Parrotta R, Jacob K, Clerbaux LA, Kreutzer S, Campbell A, Gilchrist E, Gilroy K, Rodewald AK, Honcharova-Biletska H, Schimmer R, Vélez K, Büeler S, Cammareri P, Kalna G, Wenning AS, McCoy KD, Gomez de Agüero M, Schulze-Bergkamen H, Klose C, Unger K, Macpherson AJ, Moor AE, Köhler B, Sansom OJ, Heikenwalder M, Weber A. MCL1 is Required for Maintenance of Intestinal Homeostasis and Prevention of Carcinogenesis in Mice. Gastroenterology. 2020; 159: 183-199
Kaymak I, Maier CR, Schmitz W, Campbell AD, Dankworth B, Ade CP, Walz S, Paauwe M, Kalogirou C, Marouf H, Rosenfeldt MT, Gay DM, McGregor GH, Sansom OJ, Schulze A. Mevalonate pathway provides ubiquinone to maintain pyrimidine synthesis and survival in p53-deficient cancer cells exposed to metabolic stress. Cancer research. 2020; 80:189–203
Kennedy SA, Jarboui MA, Srihari S, Raso C, Bryan K, Dernayka L, Charitou T, Bernal-Llinares M, Herrera-Montavez C, Krstic A, Matallanas D, Kotlyar M, Jurisica I, Curak J, Wong V, Stagljar I, LeBihan T, Imrie L, Pillai P, Lynn MA, Fasterius E, Al-Khalili Szigyarto C, Breen J, Kiel C, Serrano L, Rauch N, Rukhlenko O, Kholodenko BN, Iglesias-Martinez LF, Ryan CJ, Pilkington R, Cammareri P, Sansom O, Shave S, Auer M, Horn N, Klose F, Ueffing M, Boldt K, Lynn DJ, Kolch W. Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D). Nature communications. 2020; 11: 499.
Khawaja H, Campbell A, Roberts JZ, Javadi A, O'Reilly P, McArt D, Allen WL, Majkut J, Rehm M, Bardelli A, Di Nicolantonio F, Scott CJ, Kennedy R, Vitale N, Harrison T, Sansom OJ, Longley DB, Evergren E, Van Schaeybroeck S. RALB GTPase: a critical regulator of DR5 expression and TRAIL sensitivity in KRAS mutant colorectal cancer. Cell Death Dis. 2020 Oct 29;11(10):930
Knight JRP, Garland G, Pöyry T, Mead E, Vlahov N, Sfakianos A, Grosso S, De-Lima-Hedayioglu F, Mallucci GR, von der Haar T, Smales CM, Sansom OJ, Willis AE. Control of translation elongation in health and disease. Disease Models & Mechanisms. 2020; 13: dmm043208.
Maniati E, Berlato C, Gopinathan G, Heath O, Kotantaki P, Lakhani A, McDermott J, Pegrum C, Delaine-Smith RM, Pearce OMT, Hirani P, Joy JD, Szabova L, Perets R, Sansom OJ, Drapkin R, Bailey P, Balkwill FR. Mouse Ovarian Cancer Models Recapitulate the Human Tumor Microenvironment and Patient Response to Treatment. Cell reports. 2020; 30: 525-540.e527.
McGregor GH, Campbell AD, Fey SK, Tumanov S, Sumpton D, Rodriguez Blanco G, Mackay G, Nixon C, Vazquez A, Sansom OJ, Kamphorst JJ. Targeting the metabolic response to statin-mediated oxidative stress produces a synergistic anti-tumor response. Cancer research. 2020; 80:175–88
Michalopoulou E, Auciello FR, Bulusu V, Strachan D, Campbell AD, Tait-Mulder J, Karim SA, Morton JP, Sansom OJ, Kamphorst JJ. Macropinocytosis Renders a Subset of Pancreatic Tumor Cells Resistant to mTOR Inhibition. Cell reports. 2020;30:2729-2742.e2724.
Muthalagu N, Monteverde T, Raffo-Iraolagoitia X, Wiesheu R, Whyte D, Hedley A, Laing S, Kruspig B, Upstill-Goddard R, Shaw R, Neidler S, Rink C, Karim SA, Gyuraszova K, Nixon C, Clark W, Biankin AV, Carlin LM, Coffelt SB, Sansom OJ, Morton JP, Murphy DJ. Repression of the Type I Interferon pathway underlies MYC & KRAS-dependent evasion of NK & B cells in Pancreatic Ductal Adenocarcinoma. Cancer discovery. 2020;
Patel R, Brzezinska EA, Repiscak P, Ahmad I, Mui E, Gao M, Blomme A, Harle V, Tan EH, Malviya G, Mrowinska A, Loveridge CJ, Rushworth LK, Edwards J, Ntala C, Nixon C, Hedley A, Mackay G, Tardito S, Sansom OJ, Leung HY. Activation of beta-catenin cooperates with loss of Pten to drive AR-independent castration-resistant prostate cancer. Cancer research. 2020; 80:576–90
Rooney N, Mason SM, McDonald L, Däbritz JHM, Campbell KJ, Hedley A, Howard S, Athineos D, Nixon C, Clark W, Leach JDG, Sansom OJ, Edwards J, Cameron ER, Blyth K RUNX1 is a driver of renal cell carcinoma correlating with clinical outcome Cancer Res. 2020;
Roseweir AK, Park JH, Hoorn ST, Powell AG, Aherne S, Roxburgh CS, McMillan DC, Horgan PG, Ryan E, Sheahan K, Vermeulen L, Paul J, Harkin A, Graham J, Sansom O, Church DN, Tomlinson I, Saunders M, Iveson TJ, Edwards J. Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer. J Path Clin Res. 2020; 6: 283-296
Smith ALM, Whitehall JC, Bradshaw C, Gay D, Robertson F, Blain AP, Hudson G, Pyle A, Houghton D, Hunt M, Sampson JN, Stamp C, Mallett G, Amarnath S, Leslie J, Oakley F, Wilson L, Baker A, Russell OM, Johnson R, Richardson CA, Gupta B, McCallum I, McDonald SAC, Kelly S, Mathers JC, Heer R, Taylor RW, Perkins ND, Turnbull DM, Sansom OJ, Greaves LC. Age-associated mitochondrial DNA mutations cause metabolic remodeling that contributes to accelerated intestinal tumorigenesis. Nature Cancer. 2020; 1:976–989
Wilson DH, Jarman EJ, Mellin RP, Wilson ML, Waddell SH, Tsokkou P, Younger NT, Raven A, Bhalla SR, Noll ATR, Olde Damink SW, Schaap FG, Chen P, Bates DO, Banales JM, Dean CH, Henderson DJ, Sansom OJ, Kendall TJ, Boulter L. Non-canonical Wnt signalling regulates scarring in biliary disease via the planar cell polarity receptors. Nature communications. 2020; 11: 445.
Allen-Petersen BL, Risom T, Feng Z, Wang Z, Jenny ZP, Thoma MC, Pelz KR, Morton JP, Sansom OJ, Lopez CD, Sheppard B, Christensen DJ, Ohlmeyer M, Narla G, Sears RC. Activation of PP2A and inhibition of mTOR synergistically reduce MYC signaling and decrease tumor growth in pancreatic ductal adenocarcinoma. Cancer Res 2019; 79: 209-219
Cosimo E, Tarafdar A, Moles MW, Holroyd AK, Malik N, Catherwood MA, Hay J, Dunn KM, Macdonald AM, Guichard SM, O'Rourke DM, Leach MT, Sansom OJ, Cosulich SC, McCaig AM, et al. AKT/mTORC2 inhibition activates FOXO1 function in CLL cells reducing B cell receptor-mediated survival. Clin Cancer Res 2019; 25: 1574-1587
Gay DM, Ridgway RA, Mueller M, Hodder MC, Hedley A, Clark W, Leach JD, Jackstadt R, Nixon C, Huels DJ, Campbell AD, Bird TG, Sansom OJ. Loss of BCL9/9l suppresses Wnt driven tumourigenesis in models that recapitulate human cancer. Nature communications 2019; 10: 723.
Jackstadt R, van Hooff SR, Leach JD, Cortes-Lavaud X, Lohuis JO, Ridgway RA, Wouters VM, Roper J, Kendall TJ, Roxburgh CS, Horgan PG, Nixon C, Nourse C, Gunzer M, Clark W, Hedley A, Yilmaz OH, Rashid M, Bailey P, Biankin AV, Campbell AD, Adams DJ, Barry ST, Steele CW, Medema JP, Sansom OJ. Epithelial NOTCH Signaling Rewires the Tumor Microenvironment of Colorectal Cancer to Drive Poor-Prognosis Subtypes and Metastasis. Cancer cell. 2019; 36: 19-336.e317.
Johansson J, Naszai M, Hodder MC, Pickering KA, Miller BW, Ridgway RA, Yu Y, Peschard P, Brachmann S, Campbell AD, Cordero JB, Sansom OJ. RAL GTPases Drive Intestinal Stem Cell Function and Regeneration through Internalization of WNT Signalosomes. Cell Stem Cell. 2019; 24: 592-607.e7.
Kugeratski FG, Atkinson SJ, Neilson LJ, Lilla S, Knight JRP, Serneels J, Juin A, Ismail S, Bryant DM, Markert EK, Machesky LM, Mazzone M, Sansom OJ, Zanivan S. Hypoxic cancer-associated fibroblasts increase NCBP2-AS2/HIAR to promote endothelial sprouting through enhanced VEGF signaling. Science signaling 2019; 12. pii: eaan8247.
Leach J, Morton JP, Sansom OJ. Neutrophils: Homing in on the myeloid mechanisms of metastasis. Molecular immunology. 2019;110:69-76.
Liko D, Mitchell L, Campbell KJ, Ridgway RA, Jones C, Dudek K, King A, Bryson S, Stevenson D, Blyth K, Strathdee D, Morton JP, Bird TG, Knight JRP, Willis AE, Sansom OJ. Brf1 loss and not overexpression disrupts tissues homeostasis in the intestine, liver and pancreas. Cell Death Differ. 2019; 26: 2535–2550
Malik N, Dunn KM, Cassels J, Hay J, Estell C, Sansom OJ, Michie AM. mTORC1 activity is essential for erythropoiesis and B cell lineage commitment. Scientific reports. 2019; 9: 16917.
Menon M, Elliott R, Bowers L, Balan N, Rafiq R, Costa-Cabral S, Munkonge F, Trinidade I, Porter R, Campbell AD, Johnson ER, Esdar C, Buchstaller HP, Leuthner B, Rohdich F, et al. A novel tankyrase inhibitor, MSC2504877, enhances the effects of clinical CDK4/6 inhibitors. Scientific reports 2019; 9: 201.
Reader CS, Vallath S, Steele CW, Haider S, Brentnall A, Desai A, Moore KM, Jamieson NB, Chang D, Bailey P, Scarpa A, Lawlor R, Chelala C, Keyse SM, Biankin A, Morton JP, Evans TRJ, Barry ST, Sansom OJ, Kocher HM, Marshall JF. The integrin alphavbeta6 drives pancreatic cancer through diverse mechanisms and represents an effective target for therapy. The Journal of pathology. 2019; 249: 332–342
Rohwer N, Jumpertz S, Erdem M, Egners A, Warzecha KT, Fragoulis A, Kuhl AA, Kramann R, Neuss S, Rudolph I, Endermann T, Zasada C, Apostolova I, Gerling M, Kempa S, Hughes R, Lewis CE, Brenner W, Malinowski MB, Stockmann M, Schomburg L, Faller W, Sansom OJ, Tacke F, Morkel M, Cramer T. Non-canonical HIF-1 stabilization contributes to intestinal tumorigenesis. Oncogene. 2019; 38: 5670-5685.
Spender LC, Ferguson JG, Hughes GD, Davies BR, Goldberg FW, Herrera B, Taylor RG, Strathearn LS, Sansom OJ, Barry ST, Inman GJ. Preclinical evaluation of AZ12601011 and AZ12799734, inhibitors of transforming growth factor beta superfamily type 1 receptors. Mol Pharmacol 2019; 95: 222-234
Schmidt S, Gay D, Uthe FW, Denk S, Paauwe M, Matthes N, Diefenbacher ME, Bryson S, Warrander FC, Erhard F, Ade CP, Baluapuri A, Walz S, Jackstadt R, Ford C, Vlachogiannis G, Valeri N, Otto C, Schulein-Volk C, Maurus K, Schmitz W, Knight JRP, Wolf E, Strathdee D, Schulze A, Germer CT, Rosenwald A, Sansom OJ, Eilers M, Wiegering A. A MYC-GCN2-eIF2alpha negative feedback loop limits protein synthesis to prevent MYC-dependent apoptosis in colorectal cancer. Nature cell biology. 2019; 21: 1413–1424
Vennin C, Melenec P, Rouet R, Nobis M, Cazet AS, Murphy KJ, Herrmann D, Reed DA, Lucas MC, Warren SC, Elgundi Z, Pinese M, Kalna G, Roden D, Samuel M, Zaratzian A, Grey ST, Da Silva A, Leung W, Mathivanan S, Wang Y, Braithwaite AW, Christ D, Benda A, Parkin A, Phillips PA, Whitelock JM, Gill AJ, Sansom OJ, Croucher DR, Parker BL, Pajic M, Morton JP, Cox TR, Timpson P. CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan. Nature communications. 2019; 10: 3637.
Besray Unal E, Kiel C, Benisty H, Campbell A, Pickering K, Bluthgen N, Sansom OJ, Serrano L. Systems level expression correlation of Ras GTPase regulators. Cell Commun Signal. 2018; 16: 46.
Bird TG, Muller M, Boulter L, Vincent DF, Ridgway RA, Lopez-Guadamillas E, Lu WY, Jamieson T, Govaere O, Campbell AD, Ferreira-Gonzalez S, Cole AM, Hay T, Simpson KJ, Clark W, et al. TGFbeta inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence. Sci Transl Med 2018; 10: eaan1230
Burke ZD, Reed KR, Yeh SW, Meniel V, Sansom OJ, Clarke AR, Tosh D. Spatiotemporal regulation of liver development by the Wnt/beta-catenin pathway. Sci Rep 2018; 8: 2735
Candido JB, Morton JP, Bailey P, Campbell AD, Karim SA, Jamieson T, Lapienyte L, Gopinathan A, Clark W, McGhee EJ, Wang J, Escorcio-Correia M, Zollinger R, Roshani R, Drew L, Rishi L, Arkell R, Evans TRJ, Nixon C, Jodrell DI et al. CSF1R(+) Macrophages Sustain Pancreatic Tumor Growth through T Cell Suppression and Maintenance of Key Gene Programs that Define the Squamous Subtype. Cell Rep 2018; 23: 1448-60
Chou A, Froio D, Nagrial AM, Parkin A, Murphy KJ, Chin VT, Wohl D, Steinmann A, Stark R, Drury A, Walters SN, Vennin C, Burgess A, Pinese M, Chantrill LA, et al. Tailored first-line and second-line CDK4-targeting treatment combinations in mouse models of pancreatic cancer. Gut 2018; 67: 2142-55
Conway JRW, Warren SC, Herrmann D, Murphy KJ, Cazet AS, Vennin C, Shearer RF, Killen MJ, Magenau A, Melenec P, Pinese M, Nobis M, Zaratzian A, Boulghourjian A, Da Silva AM, Del Monte-Nieto G, Adam ASA, Harvey RP, Haigh JJ, Wang Y et al. Intravital Imaging to Monitor Therapeutic Response in Moving Hypoxic Regions Resistant to PI3K Pathway Targeting in Pancreatic Cancer. Cell Rep 2018; 23: 3312-26
Ferro R, Adamska A, Lattanzio R, Mavrommati I, Edling CE, Arifin SA, Fyffe CA, Sala G, Sacchetto L, Chiorino G, De Laurenzi V, Piantelli M, Sansom OJ, Maffucci T, Falasca M. GPR55 signalling promotes proliferation of pancreatic cancer cells and tumour growth in mice, and its inhibition increases effects of gemcitabine. Oncogene 2018; 37: 6368–6382
Flanagan DJ, Hodder MC, Sansom OJ. Microenvironmental cues in cancer stemness. Nat Cell Biol 2018; 20: 1102-4.
Foth M, Ismail NFB, Kung JSC, Tomlinson D, Knowles MA, Eriksson P, Sjodahl G, Salmond JM, Sansom OJ, Iwata T. FGFR3 mutation increases bladder tumorigenesis by suppressing acute inflammation. J Pathol 2018; 246: 331-343
Godfrey JD, Morton JP, Wilczynska A, Sansom OJ, Bushell MD. MiR-142-3p is downregulated in aggressive p53 mutant mouse models of pancreatic ductal adenocarcinoma by hypermethylation of its locus. Cell Death Dis 2018; 9: 644
Greenhough A, Bagley C, Heesom KJ, Gurevich DB, Gay D, Bond M, Collard TJ, Paraskeva C, Martin P, Sansom OJ, Malik K, Williams AC. Cancer cell adaptation to hypoxia involves a HIF-GPRC5A-YAP axis. EMBO Mol Med. 2018 10: e8699
Huels DJ, Bruens L, Hodder MC, Cammareri P, Campbell AD, Ridgway RA, Gay DM, Solar-Abboud M, Faller WJ, Nixon C, Zeiger LB, McLaughlin ME, Morrissey E, Winton DJ, Snippert HJ, van Rheenen J, Sansom OJ. Wnt ligands influence tumour initiation by controlling the number of intestinal stem cells. Nat Commun 2018; 9: 1132
Malik N, Sansom OJ, Michie AM. The role of mTOR-mediated signals during haemopoiesis and lineage commitment. Biochem Soc Trans 2018; 46: 1313–1324.
Martin KJ, McGhee EJ, Schwarz JP, Drysdale M, Brachmann SM, Stucke V, Sansom OJ, Anderson KI. Accepting from the best donor; analysis of long-lifetime donor fluorescent protein pairings to optimise dynamic FLIM-based FRET experiments. PLoS One 2018; 13: e0183585
May S, Owen H, Phesse TJ, Greenow KR, Jones GR, Blackwood A, Cook PC, Towers C, Gallimore AM, Williams GT, Sturzl M, Britzen-Laurent N, Sansom OJ, MacDonald AS, Bird AP, Clarke AR, Parry L. Mbd2 enables tumourigenesis within the intestine while preventing tumour-promoting inflammation. J Pathol 2018; 245: 270-82
Monteverde T, Tait-Mulder J, Hedley A, Knight JR, Sansom OJ, Murphy DJ. Calcium signalling links MYC to NUAK1. Oncogene 2018; 37: 982-92
Morris HT, Fort L, Spence HJ, Patel R, Vincent DF, Park JH, Snapper SB, Carey FA, Sansom OJ, Machesky LM. Loss of N-WASP drives early progression in an Apc model of intestinal tumourigenesis. J Pathol 2018; 245: 337-48
Patel R, Fleming J, Mui E, Loveridge C, Repiscak P, Blomme A, Harle V, Salji M, Ahmad I, Teo K, Hamdy FC, Hedley A, van den Broek N, Mackay G, Edwards J, Sansom OJ, Leung HY. Sprouty2 loss-induced IL6 drives castration-resistant prostate cancer through scavenger receptor B1. EMBO Mol Med 2018; 10: e8347
Pearson HB, Li J, Meniel VS, Fennell CM, Waring P, Montgomery KG, Rebello RJ, Macpherson AA, Koushyar S, Furic L, Cullinane C, Clarkson RW, Smalley MJ, Simpson KJ, Phesse TJ, Shepherd PR, Humbert PO, Sansom OJ, Phillips WA. Identification of Pik3ca Mutation as a Genetic Driver of Prostate Cancer That Cooperates with Pten Loss to Accelerate Progression and Castration-Resistant Growth. Cancer Discov 2018; 8: 764-79
Port J, Muthalagu N, Raja M, Ceteci F, Monteverde T, Kruspig B, Hedley A, Kalna G, Lilla S, Neilson L, Brucoli M, Gyuraszova K, Tait-Mulder J, Mezna M, Svambaryte S, Bryson A, Sumpton D, McVie A, Nixon C, Drysdale M et al. Colorectal Tumors Require NUAK1 for Protection from Oxidative Stress. Cancer Discov 2018; 8: 632-47
Vlachogiannis G, Hedayat S, Vatsiou A, Jamin Y, Fernandez-Mateos J, Khan K, Lampis A, Eason K, Huntingford I, Burke R, Rata M, Koh DM, Tunariu N, Collins D, Hulkki-Wilson S, Ragulan C, Spiteri I, Moorcraft SY, Chau I, Rao S et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science 2018; 359: 920-6
Woroniuk A, Porter A, White G, Newman DT, Diamantopoulou Z, Waring T, Rooney C, Strathdee D, Marston DJ, Hahn KM, Sansom OJ, Zech T, Malliri A. STEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap. Nat Commun 2018; 9: 2124
Ahmad I, Sansom OJ. Role of Wnt signalling in advanced prostate cancer. J Pathol 2018; 245: 3-5
Hodder MC, Flanagan DJ, Sansom OJ. Intestinal Stem Cell Dynamics: A Story of Mice and Humans. Cell Stem Cell 2018; 22: 785-7
Andrew Campbell
Rachel Ridgway
Constantinos Alexandrou
Patricia Centeno
Nuray Gunduz
Andrew Hartley
Georgios Kanellos
Nadia Nasreddin
Alexander Raven
Santi Susanti
Nikola Vlahov
Lucas Zeiger
Kathryn Gilroy
Rosalin Simpson
Hannah Tovell
Catriona Ford
Abdullah Alyamani
Tam Jamieson
Ayse Yazgilli
Narthana Ilenkovan
Kyrillus Shohdy
Wing Yu Ho
Laura Millett
Megan Mills
Teena Thakur (joint with Ross Cagan)
Sarah Williams
Nathalie Sphyris
Cancer associated fibroblasts (CAFs) have emerged as a promising therapeutic target in cancer because it is now well established that they actively contribute to tumour pathology. CAFs are a unique cell type in that they are highly secretory, and their secretome dictates the structure of a tumour and influences the behaviour of cancer cells and other cell types.
With our research we want to understand the molecular mechanisms through which CAFs alter the tumour microenvironment (TME) to influence cancer aggressiveness and resistance to therapy.
High-grade serous ovarian cancer and triple negative breast cancer are the major focus of our research because there are limited therapies against the cancer cells of these tumour types. However, CAFs are highly abundant in these tumours, and our overarching goal is to find ways to target CAFs in combination with other anti-cancer therapies to improve survival of cancer patients.
In the last few years, our work has described unprecedented ways through which CAFs create a TME that supports tumour invasion and metastasis by altering the structure of the extracellular matrix (ECM), and tumour blood vessels' and cancer cells' functions. A major focus of our on-going research is the metabolism of CAFs. We have found that cell metabolism is a major epigenetic regulator of CAF functions and that it can influence the translation of pro-tumorigenic ECM proteins. Our on-going research aims to investigate these aspects further and to understand how targeting specific metabolic pathways affects the composition and structure of the ECM and the immune-TME, and whether it can be exploited to halt cancer progression and improve effectiveness of conventional therapeutic treatments.
Our research is unique in that we mostly work with patient-derived cells that we generate in the lab from tissues that patients kindly donate to research. We also work with pre-clinical models relevant for ovarian and breast cancer. Moreover, because of our established expertise in mass spectrometry (MS)-proteomics, we develop tailored technology to study CAF biology, including their crosstalk signalling with other cell types in co-cultures in vitro and their metabolism in vivo.
Recently, we have joined the effort to improve early detection of cancer in patients, since detecting cancer at an early stage can dramatically increase opportunities for curative intervention. To tackle this challenge, we are developing novel MS proteomic-based technology for biomarker discovery in body fluids. This research is funded by the CRUK Early Detection and Diagnosis Research scheme.
pdf Zanivan Lab Report (102 KB)
Kugeratski FG, Atkinson SJ, Neilson LJ, Lilla S, Knight JRP, Serneels J, Juin A, Ismail S, Bryant DM, Markert EK, Machesky LM, Mazzone M, Sansom OJ, Zanivan S. Hypoxic cancer-associated fibroblasts increase NCBP2-AS2/HIAR to promote endothelial sprouting through enhanced VEGF signaling. Science signaling 2019; 12: eaan8247
van der Reest J, Lilla S, Zheng L*, Zanivan S*, Gottlieb E*. Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress. Nat Commun. 2018; 9: 1581
Hernandez-Fernaud JR, Ruengeler E, Casazza A, Neilson LJ, Pulleine E, Santi A, Ismail S, Lilla S, Dhayade S, MacPherson IR, McNeish I, Ennis D, Ali H, Kugeratski FG, Al Khamici H, van den Biggelaar M, van den Berghe PV, Cloix C, McDonald L, Millan D et al. Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity. Nat Commun 2017; 8: 14206
Reid SE, Kay EJ, Neilson LJ, Henze AT, Serneels J, McGhee EJ, Dhayade S, Nixon C, Mackey JB, Santi A, Swaminathan K, Athineos D, Papalazarou V, Patella F, Roman-Fernandez A, ElMaghloob Y, Hernandez-Fernaud JR, Adams RH, Ismail S, Bryant DM et al. Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium. EMBO J. 2017; 36: 2373-89
2006: PhD, Complex Systems Applied to Post Genomic Biology, University of Torino, Italy
2002: Master in Bioinformatics, University of Torino, Italy
2001: MS in Biology, University of Torino, Italy
2010-present: Group Leader, CRUK Scotland Institute
2014-present Head of Proteomics Advanced Technology, CRUK Scotland Institute
2007-2010: Postdoctoral Fellow with Matthias Mann, Max Planck Institute of Biochemistry, Martinsried, Germany
2002-2006: PhD Student with Guido Serini and Federico Bussolino, Candiolo Cancer Institute IRCCS, Torino, Italy
Ackermann T, Shokry E, Deshmukh R, Anand J, Galbraith LCA, Mitchell L, Rodriguez-Blanco G, Villar VH, Sterken BA, Nixon C, Zanivan S, Blyth K, Sumpton D, Tardito S. Breast cancer secretes anti-ferroptotic MUFAs and depends on selenoprotein synthesis for metastasis. bioRxiv. 2024:2023.2006.2013.544588.
Dawson A, Zarou MM, Prasad B, Bittencourt-Silvestre J, Zerbst D, Himonas E, Hsieh YC, van Loon I, Blanco GR, Ianniciello A, Kerekes Z, Krishnan V, Agarwal P, Almasoudi H, McCluskey L, Hopcroft LEM, Scott MT, Baquero P, Dunn K, Vetrie D, Copland M, Bhatia R, Coffelt SB, Tiong OS, Wheadon H, Zanivan S, Kirschner K, Helgason GV. Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche. Nat Commun. 2024;15(1):1090.
Gounis M, Campos AV, Shokry E, Mitchell L, Dornier E, Rooney N, Dhayade S, Pardo L, Moore M, Novo D, Mowat J, Jamieson C, Kay E, Zanivan S, Nixon C, Macpherson I, Tardito S, Sumpton D, Blyth K, Norman JC, Clarke CJ. Metabolic adaptations of micrometastases alter EV production to generate invasive microenvironments. bioRxiv. 2024:2024.2005.2012.593552.
Mahmood M, Liu EM, Shergold AL, Tolla E, Tait-Mulder J, Huerta-Uribe A, Shokry E, Young AL, Lilla S, Kim M, Park T, Boscenco S, Manchon JL, Rodríguez-Antona C, Walters RC, Springett RJ, Blaza JN, Mitchell L, Blyth K, Zanivan S, Sumpton D, Roberts EW, Reznik E, Gammage PA. Mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade response in melanoma. Nat Cancer. 2024.
Sanchez-Lopez I, Orantos-Aguilera Y, Pozo-Guisado E, Alvarez-Barientos A, Lilla S, Zanivan S, Lachaud C, Martin-Romero FJ. STIM1 translocation to the nucleus protects cells from DNA damage. Nucleic Acids Res. 2024.
Santi A, Kay EJ, Neilson LJ, McGarry L, Lilla S, Mullin M, Paul NR, Fercoq F, Koulouras G, Rodriguez Blanco G, Athineos D, Mason S, Hughes M, Thomson G, Kieffer Y, Nixon C, Blyth K, Mechta-Grigoriou F, Carlin LM, Zanivan S. Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Sci Signal. 2024;17(827):eade0580.
Vringer E, Heilig R, Riley JS, Black A, Cloix C, Skalka G, Montes-Gómez AE, Aguado A, Lilla S, Walczak H, Gyrd-Hansen M, Murphy DJ, Huang DT, Zanivan S, Tait SW. Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO J. 2024.
Whitelaw JA, Lilla S, Nikolaou S, Tweedy L, Fort L, Paul NR, Zanivan S, Gadegaard N, Insall RH, Machesky LM. CYRI-B loss promotes enlarged mature focal adhesions and restricts microtubule and ERC1 access to the cell leading edge. bioRxiv. 2024:2024.2003.2026.586838.
Ackermann T, Shokry E, Deshmukh R, Anand J, Galbraith LCA, Mitchell L, Rodriguez-Blanco G, Villar VH, Sterken BA, Nixon C, Zanivan S, Blyth K, Sumpton D, Tardito S. Paracrine secretion of MUFAs prevents ferroptosis in triple-negative breast cancer and reveals selenocysteine synthesis dependency for lung metastasis. bioRxiv. 2023;Volume:2023.2006.2013.544588.
Altea-Manzano P, Doglioni G, Liu Y, Cuadros AM, Nolan E, Fernández-García J, Wu Q, Planque M, Laue KJ, Cidre-Aranaz F, Liu XZ, Marin-Bejar O, Van Elsen J, Vermeire I, Broekaert D, Demeyer S, Spotbeen X, Idkowiak J, Montagne A, Demicco M, Alkan HF, Rabas N, Riera-Domingo C, Richard F, Geukens T, De Schepper M, Leduc S, Hatse S, Lambrechts Y, Kay EJ, Lilla S, Alekseenko A, Geldhof V, Boeckx B, de la Calle Arregui C, Floris G, Swinnen JV, Marine JC, Lambrechts D, Pelechano V, Mazzone M, Zanivan S, Cools J, Wildiers H, Baud V, Grünewald TGP, Ben-David U, Desmedt C, Malanchi I, Fendt SM. A palmitate-rich metastatic niche enables metastasis growth via p65 acetylation resulting in pro-metastatic NF-κB signaling. Nat Cancer. 2023; 4: 344–364
Kugeratski F, LeBleu V, Dowlatshahi D, Sugimoto H, Arian K, Fan Y, Huang L, Wills D, Lilla S, Hodge K, Zanivan S, McAndrews K, Kalluri R. Engineered immunomodulatory extracellular vesicles derived from epithelial cells acquire capacity for positive and negative T cell co-stimulation in cancer and autoimmunity. bioRxiv. 2023:2023.2011.2002.565371.
Mahmood M, Liu EM, Shergold AL, Tolla E, Tait-Mulder J, Uribe AH, Shokry E, Young AL, Lilla S, Kim M, Park T, Manchon JL, Rodriguez-Antona C, Walters RC, Springett RJ, Blaza JN, Zanivan S, Sumpton DA, Roberts EW, Reznik E, Gammage PA. Tumour mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade. bioRxiv. 2023;Volume:2023.2003.2021.533091.
Moore M, Pardo L, Mitchell L, Schmidt T, May S, Mueller M, Strathdee D, Bryson S, Hodge K, Lilla S, Zanivan S, Waldron J, McGarry L, Peter-Durairaj R, Kanellos G, Nixon C, Ballantyne F, LeQuesne J, Sansom OJ, Bird T, Bushell M, Norman JC. The eIF4A2 negative regulator of mRNA translation promotes extracellular matrix deposition to accelerate hepatocellular carcinoma initiation. bioRxiv. 2023;Volume:2023.2008.2016.553544.
Nikolatou K, Sandilands E, Román-Fernández A, Cumming EM, Freckmann E, Lilla S, Buetow L, McGarry L, Neilson M, Shaw R, Strachan D, Miller C, Huang DT, McNeish IA, Norman JC, Zanivan S, Bryant DM. PTEN deficiency exposes a requirement for an ARF GTPase module for integrin-dependent invasion in ovarian cancer. The EMBO Journal. 2023;n/a:e113987.
Román-Fernández A, Mansour MA, Kugeratski FG, Anand J, Sandilands E, Galbraith L, Rakovic K, Freckmann EC, Cumming EM, Park J, Nikolatou K, Lilla S, Shaw R, Strachan D, Mason S, Patel R, McGarry L, Katoch A, Campbell KJ, Nixon C, Miller CJ, Leung HY, Le Quesne J, Norman JC, Zanivan S, Blyth K, Bryant DM. Spatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function. Sci Adv. 2023;9:eabq1858.
Santi A, Kay EJ, Neilson LJ, McGarry L, Lilla S, Mullin M, Paul NR, Fercoq F, Koulouras G, Blanco GR, Athineos D, Mason S, Hughes M, Kieffer Y, Nixon C, Blyth K, Mechta-Grigoriou F, Carlin LM, Zanivan S. Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. bioRxiv. 2023;Volume:2023.2001.2013.523951.
Schmidt T, Dabrowska A, Waldron JA, Hodge K, Koulouras G, Gabrielsen M, Munro J, Tack DC, Harris G, McGhee E, Scott D, Carlin Leo M, Huang D, Le Quesne J, Zanivan S, Wilczynska A, Bushell M. eIF4A1-dependent mRNAs employ purine-rich 5’UTR sequences to activate localised eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation. Nucleic Acids Research. 2023; 51: 1859–1879
Singh SP, Smyth DJ, Cunningham K, Mukundan A, Byeon C-H, Hinck CS, White MPJ, Ciancia C, Wosowska N, Sanders A, Jin R, Lilla S, Zanivan S, Schoenherr C, Inman G, Dinther Mv, Dijke Pt, Hinck AP, Maizels RM. The helminth TGF-β mimic TGM4 is a modular ligand that binds CD44, CD49d and TGF-β receptors to preferentially target myeloid cells. bioRxiv. 2023:2023.2011.2013.566701.
Subramaniam G, Schleicher K, Kovanich D, Zerio A, Folkmanaite M, Chao YC, Surdo NC, Koschinski A, Hu J, Scholten A, Heck AJR, Ercu M, Sholokh A, Chan Park K, Klussmann E, Meraviglia V, Bellin M, Zanivan S, Hester S, Mohammed S, Zaccolo M. Integrated Proteomics Unveils Nuclear PDE3A2 as a Regulator of Cardiac Myocyte Hypertrophy. Circ Res. 2023;132:828–848
Kay EJ, Zanivan S. Bicarbonate transport as regulator of anti-tumour immunity in pancreatic cancer. Mol Oncol. 2023;17:541-544
Kay EJ, Zanivan S, Rufini A. Proline metabolism shapes the tumor microenvironment: from collagen deposition to immune evasion. Curr Opin Biotechnol. 2023:103011.
Baudot AD, Wang VM, Leach JD, O'Prey J, Long JS, Paulus-Hock V, Lilla S, Thomson DM, Greenhorn J, Ghaffar F, Nixon C, Helfrich MH, Strathdee D, Pratt J, Marchesi F, Zanivan S, Ryan KM. Glycan degradation promotes macroautophagy. Proc Natl Acad Sci U S A. 2022;119(26):e2111506119.
Blomme A, Peter C, Mui E, Rodriguez Blanco G, An N, Mason LM, Jamieson LE, McGregor GH, Lilla S, Ntala C, Patel R, Thiry M, Kung SHY, Leclercq M, Ford CA, Rushworth LK, McGarry DJ, Mason S, Repiscak P, Nixon C, Salji MJ, Markert E, MacKay GM, Kamphorst JJ, Graham D, Faulds K, Fazli L, Gleave ME, Avezov E, Edwards J, Yin H, Sumpton D, Blyth K, Close P, Murphy DJ, Zanivan S, Leung HY. THEM6-mediated reprogramming of lipid metabolism supports treatment resistance in prostate cancer. EMBO Molecular Medicine. 2022;14:e14764
Camargo L, Samji S, Lilla S, Zanivan S, Bulleid N, Hartley R, Delles C, Leiper J, Fuller W, Montezano A, Touyz R. Proteomic profile of cysteine oxidation in vacsular smooth muscle cells in human hypertension. J Hypertens. 2022;40:e225-e226.
Gioelli N, Neilson LJ, Wei N, Villari G, Chen W, Kuhle B, Ehling M, Maione F, Willox S, Brundu S, Avanzato D, Koulouras G, Mazzone M, Giraudo E, Yang XL, Valdembri D, Zanivan S, Serini G. Neuropilin 1 and its inhibitory ligand mini-tryptophanyl-tRNA synthetase inversely regulate VE-cadherin turnover and vascular permeability. Nat Commun. 2022;13:4188.
Kay EJ, Paterson K, Riero-Domingo C, Sumpton D, Däbritz JHM, Tardito S, Boldrini C, Hernandez-Fernaud JR, Athineos D, Dhayade S, Stepanova E, Gjerga E, Neilson LJ, Lilla S, Hedley A, Koulouras G, McGregor G, Jamieson C, Johson RM, Park M, Kirschner K, Miller C, Kamphorst JJ, Loayza-Puch F, Saez-Rodriguez J, Mazzone M, Blyth K, Zagoni M, Zanivan S. Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix. Nature Metabolism. 2022;4(6):693-710.
McGarry DJ, Castino G, Lilla S, Carnet A, Kelly L, Micovic K, Zanivan S, Olson MF. MICAL1 activation by PAK1 mediates actin filament disassembly. Cell Reports. 2022;41:111442
Närvä E, Taskinen ME, Lilla S, Isomursu A, Pietilä M, Weltner J, Isola J, Sihto H, Joensuu H, Zanivan S, Norman J, Ivaska J. MASTL is enriched in cancerous and pluripotent stem cells and influences OCT1/OCT4 levels. iScience. 2022;25:104459.
Nikolatou K, Sandilands E, Roman-Fernandez A, Cumming EM, Freckmann EC, Lilla S, Buetow L, McGarry L, Neilson M, Shaw R, Strachan D, Miller C, Huang DT, McNeish IA, Norman JC, Zanivan S, Bryant D. PTEN deficiency exposes a requirement for an ARF GTPase module in integrin-dependent invasion in ovarian cancer. bioRxiv. 2022;Volume:2022.2011.2029.518198.
Salji MJ, Blomme A, Däbritz JHM, Repiscak P, Lilla S, Patel R, Sumpton D, van den Broek NJF, Daly R, Zanivan S, Leung HY. Multi-omics & pathway analysis identify potential roles for tumor N-acetyl aspartate accumulation in murine models of castration-resistant prostate cancer. iScience. 2022;25:104056.
Schmidt T, Dabrowska A, Waldron JA, Hodge K, Koulouras G, Gabrielsen M, Munro J, Tack DC, Harris G, McGhee E, Scott D, Carlin LM, Huang D, Le Quesne J, Zanivan S, Wilczynska A, Bushell M. Purine-rich RNA sequences in the 5’UTR site-specifically regulate eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation. bioRxiv. 2022;Volume:2022.2008.2008.503179.
Kay EJ, Zanivan S. Methylmalonic acid: an age-related metabolite that drives tumour aggressiveness. Nat Metab. 2022; 4:412–413
Kugeratski FG, Santi A, Zanivan S. Extracellular vesicles as central regulators of blood vessel function in cancer. Science Signaling. 2022;15(753):eaaz4742.
Ahmed SF, Buetow L, Gabrielsen M, Lilla S, Sibbet GJ, Sumpton D, Zanivan S, Hedley A, Clark W, Huang DT. E3 ligase-inactivation rewires CBL interactome to elicit oncogenesis by hijacking RTK-CBL-CIN85 axis. Oncogene. 2021;40(12):2149-2164.
Budden T, Gaudy-Marqueste C, Porter A, Kay E, Gurung S, Earnshaw CH, Roeck K, Craig S, Traves V, Krutmann J, Muller P, Motta L, Zanivan S, Malliri A, Furney SJ, Nagore E, Virós A. Ultraviolet light-induced collagen degradation inhibits melanoma invasion. Nat Commun. 2021;12:2742.
Gillen SL, Giacomelli C, Hodge K, Zanivan S, Bushell M, Wilczynska A. Differential regulation of mRNA fate by the human Ccr4-Not complex is driven by coding sequence composition and mRNA localization. Genome Biol. 2021;22:284.
Kugeratski FG, Hodge K, Lilla S, McAndrews KM, Zhou X, Hwang RF, Zanivan S, Kalluri R. Quantitative proteomics identifies the core proteome of exosomes with syntenin-1 as the highest abundant protein and a putative universal biomarker. Nat Cell Biol. 2021;23(6):631-641.
Mackey JBG, McFarlane AJ, Jamieson T, Jackstadt R, Raffo-Iraolagoitia XL, Secklehner J, Cortes-Lavaud X, Fercoq F, Clarke W, Hedley A, Gilroy K, Lilla S, Vuononvirta J, Graham GJ, De Filippo K, Murphy DJ, Steele CW, Norman JC, Bird TG, Mann DA, Morton JP, Zanivan S, Sansom OJ, Carlin LM. Maturation, developmental site, and pathology dictate murine neutrophil function. bioRxiv. 2021.
Marco S, Neilson M, Moore M, Perez-Garcia A, Hall H, Mitchell L, Lilla S, Blanco GR, Hedley A, Zanivan S, Norman JC. Nuclear-capture of endosomes depletes nuclear G-actin to promote SRF/MRTF activation and cancer cell invasion. Nat Commun. 2021 Nov 24;12(1):6829.
Martinez RS, Salji MJ, Rushworth L, Ntala C, Rodriguez Blanco G, Hedley A, Clark W, Peixoto P, Hervouet E, Renaude E, Kung SHY, Galbraith LCA, Nixon C, Lilla S, Mackay GM, Fazli L, Gaughan L, Sumpton D, Gleave ME, Zanivan S, Blomme A, Leung HY. SLFN5 regulates LAT1-mediated mTOR activation in castration-resistant prostate cancer. Cancer Res. 2021;81: 3664–78
Nacke M, Sandilands E, Nikolatou K, Román-Fernández Á, Mason S, Patel R, Lilla S, Yelland T, Galbraith LCA, Freckmann EC, McGarry L, Morton JP, Shanks E, Leung HY, Markert E, Ismail S, Zanivan S, Blyth K, Bryant DM. An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism. Nat Commun. 2021;12:1623.
Phatak V, von Grabowiecki Y, Janus J, Officer L, Behan C, Aschauer L, Pinon L, Mackay H, Zanivan S, Norman JC, Kelly M, Le Quesne J, Muller PAJ. Mutant p53 promotes RCP-dependent chemoresistance coinciding with increased delivery of P-glycoprotein to the plasma membrane. Cell Death Dis. 2021;12(2):207.
Domen A, Quatannens D, Zanivan S, Deben C, Van Audenaerde J, Smits E, Wouters A, Lardon F, Roeyen G, Verhoeven Y, Janssens A, Vandamme T, van Dam P, Peeters M, Prenen H. Cancer-Associated Fibroblasts as a Common Orchestrator of Therapy Resistance in Lung and Pancreatic Cancer. Cancers (Basel). 2021;13:987
Kay EJ, Koulouras G, Zanivan S. Regulation of Extracellular Matrix Production in Activated Fibroblasts: Roles of Amino Acid Metabolism in Collagen Synthesis. Front Oncol. 2021;11:719922.
Kay EJ, Zanivan S. Metabolic pathways fuelling protumourigenic cancer-associated fibroblast functions. Current Opinion in Systems Biology. 2021;28:100377.
Kay EJ, Zanivan S. Two opposing sub-populations of fibroblasts decide progression of pancreatic cancer. Cancer Cell. 2021; 39:1175-1177.
Paterson K, Zanivan S, Glasspool R, Coffelt SB, Zagnoni M. Microfluidic technologies for immunotherapy studies on solid tumours. Lab Chip. 2021;21:2306-2329.
Ahmed SF, Buetow L, Gabrielsen M, Lilla S, Chatrin C, Sibbet GJ, Zanivan S, Huang DT. DELTEX2 C-terminal domain recognizes and recruits ADP-ribosylated proteins for ubiquitination. Science Advances. 2020;6(34):eabc0629.
Blomme A, Ford CA, Mui E, Patel R, Ntala C, Jamieson LE, Planque M, McGregor GH, Peixoto P, Hervouet E, Nixon C, Salji M, Gaughan L, Markert E, Repiscak P, Sumpton D, Rodriguez Blanco G, Lilla S, Kamphorst JJ, Graham D, Faulds K, MacKay GM, Fendt S-M, Zanivan S, Leung HY. 2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer. Nat Commun. 2020; 11: 2508
Cao X, Lilla S, Cao Z, Pringle MA, Oka OBV, Robinson PJ, Szmaja T, van Lith M, Zanivan S, Bulleid NJ. The mammalian cytosolic thioredoxin reductase pathway acts via a membrane protein to reduce ER-localised proteins. Journal of cell science. 2020;
Lobo MJ, Reverte-Salisa L, Chao YC, Koschinski A, Gesellchen F, Subramaniam G, Jiang H, Pace S, Larcom N, Paolocci E, Pfeifer A, Zanivan S, Zaccolo M. Phosphodiesterase 2A2 regulates mitochondria clearance through Parkin-dependent mitophagy. Commun Biol. 2020;3(1):596.
Loveridge CJ, Slater S, Campbell KJ, Nam NA, Knight J, Ahmad I, Hedley A, Lilla S, Repiscak P, Patel R, Salji M, Fleming J, Mitchell L, Nixon C, Strathdee D, Neilson M, Ntala C, Bryson S, Zanivan S, Edwards J, Robson CN, Goodyear CS, Blyth K, Leung HY. BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration. Oncogene. 2020; 39: 1797–1806
Oizel K, Tait-Mulder J, Fernandez-de-Cossio-Diaz J, Pietzke M, Brunton H, Lilla S, Dhayade S, Athineos D, Blanco GR, Sumpton D, Mackay GM, Blyth K, Zanivan SR, Meiser J, Vazquez A. Formate induces a metabolic switch in nucleotide and energy metabolism. Cell death & disease. 2020;11:310.
Tait-Mulder J, Hodge K, Sumpton D, Zanivan S, Vazquez A. The conversion of formate into purines stimulates mTORC1 leading to CAD-dependent activation of pyrimidine synthesis. Cancer & Metabolism. 2020;8(1):20.
Taskinen ME, Närvä E, Conway JRW, Hinojosa LS, Lilla S, Mai A, De Franceschi N, Elo LL, Grosse R, Zanivan S, Norman JC, Ivaska J. MASTL promotes cell contractility and motility through kinase-independent signaling. J Cell Biol. 2020;219:e201906204
Unbekandt M, Lilla S, Zanivan S, Olson MF. The CDC42 effector protein MRCKβ autophosphorylates on Threonine 1108. Small GTPases. 2020;11(6):451-460.
Ferraro DA, Patella F, Zanivan S, Donato C, Aceto N, Giannotta M, Dejana E, Diepenbruck M, Christofori G, Buess M. Endothelial cell-derived nidogen-1 inhibits migration of SK-BR-3 breast cancer cells. BMC Cancer. 2019; 19: 312.
Kugeratski FG, Atkinson SJ, Neilson LJ, Lilla S, Knight JRP, Serneels J, Juin A, Ismail S, Bryant DM, Markert EK, Machesky LM, Mazzone M, Sansom OJ, Zanivan S. Hypoxic cancer-associated fibroblasts increase NCBP2-AS2/HIAR to promote endothelial sprouting through enhanced VEGF signaling. Science signaling 2019; 12: eaan8247.
Whitelaw JA, Lilla S, Paul NR, Fort L, Zanivan S, Machesky LM. CYRI/ Fam49 Proteins Represent a New Class of Rac1 Interactors. Communicative & integrative biology. 2019;12:112-118.
Wilczynska A, Gillen SL, Schmidt T, Meijer HA, Jukes-Jones R, Langlais C, Kopra K, Lu WT, Godfrey JD, Hawley BR, Hodge K, Zanivan S, Cain K, Le Quesne J, Bushell M. eIF4A2 drives repression of translation at initiation by Ccr4-Not through purine-rich motifs in the 5'UTR. Genome Biol. 2019; 20: 262.
Dandoulaki M, Petsalaki E, Sumpton D, Zanivan S, Zachos G. Src activation by Chk1 promotes actin patch formation and prevents chromatin bridge breakage in cytokinesis. J Cell Biol 2018; 217: 3071–3089
Fort L, Batista JM, Thomason PA, Spence HJ, Whitelaw JA, Tweedy L, Greaves J, Martin KJ, Anderson KI, Brown P, Lilla S, Neilson MP, Tafelmeyer P, Zanivan S, Ismail S, Bryant DM, Tomkinson NCO, Chamberlain LH, Mastick GS, Insall RH, Machesky LM. Fam49/CYRI interacts with Rac1 and locally suppresses protrusions. Nat Cell Biol. 2018 ; 20: 1159-71.
Kugeratski FG, Batista M, Lima CVP, Neilson LJ, da Cunha ES, de Godoy LM, Zanivan S, Krieger MA, Marchini FK. Mitogen-Activated Protein Kinase Kinase 5 Regulates Proliferation and Biosynthetic Processes in Procyclic Forms of Trypanosoma brucei. J Proteome Res 2018; 17: 108-18.
Novo D, Heath N, Mitchell L, Caligiuri G, MacFarlane A, Reijmer D, Charlton L, Knight J, Calka M, McGhee E, Dornier E, Sumpton D, Mason S, Echard A, Klinkert K, et al. Mutant p53s generate pro-invasive niches by influencing exosome podocalyxin levels. Nat Commun 2018; 9: 5069.
Port J, Muthalagu N, Raja M, Ceteci F, Monteverde T, Kruspig B, Hedley A, Kalna G, Lilla S, Neilson L, Brucoli M, Gyuraszova K, Tait-Mulder J, Mezna M, Svambaryte S, et al. Colorectal Tumors Require NUAK1 for Protection from Oxidative Stress. Cancer Discov 2018;8(5):632-47
van der Reest J, Lilla S, Zheng L, Zanivan S, Gottlieb E. Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress. Nat Commun 2018; 9: 1581.
Santi A, Kugeratski FG, Zanivan S. Cancer Associated Fibroblasts: The Architects of Stroma Remodeling. Proteomics 2018; 18: e1700167.
Diaz-Vera J, Palmer S, Hernandez-Fernaud JR, Dornier E, Mitchell LE, Macpherson I, Edwards J, Zanivan S, Norman JC. A proteomic approach to identify endosomal cargoes controlling cancer invasiveness. J Cell Sci 2017; 130: 697-711
Hernandez-Fernaud JR, Ruengeler E, Casazza A, Neilson LJ, Pulleine E, Santi A, Ismail S, Lilla S, Dhayade S, MacPherson IR, McNeish I, Ennis D, Ali H, Kugeratski FG, Al Khamici H, van den Biggelaar M, van den Berghe PV, Cloix C, McDonald L, Millan D et al. Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity. Nat Commun 2017; 8: 14206
Reid SE, Kay EJ, Neilson LJ, Henze AT, Serneels J, McGhee EJ, Dhayade S, Nixon C, Mackey JB, Santi A, Swaminathan K, Athineos D, Papalazarou V, Patella F, Roman-Fernandez A, ElMaghloob Y, Hernandez-Fernaud JR, Adams RH, Ismail S, Bryant DM et al. Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium. EMBO 2017; 36: 2373-89
van den Eshof BL, Hoogendijk AJ, Simpson PJ, van Alphen FPJ, Zanivan S, Mertens K, Meijer AB, van den Biggelaar M. Paradigm of Biased PAR1 (Protease-Activated Receptor-1) Activation and Inhibition in Endothelial Cells Dissected by Phosphoproteomics. Arterioscler Thromb Vasc Biol 2017; 37: 1891-1902
Norman J, Zanivan S (2017) Chloride intracellular channel 3: A secreted pro-invasive oxidoreductase. Cell Cycle: 16; 1993-4
Reid SE, Zanivan S. Tumor stiffness extends its grip on the metastatic microenvironment. Mol Cell Oncol 2017; 4: e1372866
Patella F, Neilson LJ, Athineos D, Erami Z, Anderson KI, Blyth K, Ryan KM, Zanivan S. In-Depth Proteomics Identifies a Role for Autophagy in Controlling Reactive Oxygen Species Mediated Endothelial Permeability. J Proteome Res. 2016; 15: 2187-97
Clarke CJ, Berg TJ, Birch J, Ennis D, Mitchell L, Cloix C, Campbell A, Sumpton D, Nixon C, Campbell K, Bridgeman VL, Vermeulen PB, Foo S, Kostaras E, Jones JL, Haywood L, Pulleine E, Yin HB, Strathdee D, Sansom O, Blyth K, McNeish I, Zanivan S, Reynolds AR, Norman JC. The Initiator Methionine tRNA Drives Secretion of Type II Collagen from Stromal Fibroblasts to Promote Tumor Growth and Angiogenesis. Curr Biol. 2016; 26: 755-65
Paula Duch Gili
Emily Kay
Britt Sterken
Ashton Theakstone
Maja Bailey
Lisa Neilson
Douglas Cartwright
Kunal Reshamwala
Fernanda Kugeratski (Post-doc, MD Anderson, USA)
Francesca Patella (Post-doc, University College London, UK)
Juan Ramon Hernandez (Manager Proteomic Facility, University of Warwick, UK)
Steven Reid (Post-doc, Lund University, SE)
Maartje van den Biggelaar (Scientist, Sanquin Research, Amsterdam, NL)
Our lab focuses on a fundamental, yet largely unanswered question: How is the normal organisation of tissue disrupted to allow cells to form disarrayed tumours?
Cells of many tissues are polarised. That is that cells collectively form configurations tailored to the needs of a tissue. During tumourigenesis this exquisite organisation is lost. Despite the loss of tissue polarity being an obligate event in cancer progression, we know little about this basic process.
We use mini-avatars of tumours ex vivo to understand how cells collectively organise. Our efforts are focused on colorectal and prostate cancers. We take two approaches to unravel the complexity of this process:
1) building new tools to analyse tumour avatars ex vivo, and
2) identifying the signalling processes that drive collective tumour invasion and metastasis. We collaborate extensively for a multi-disciplinary approach to understand tumour metastasis (Sansom, Zanivan, Blyth, Leung, Miller Labs @ CRUK Scotland Institute).
To develop better tools to understand how tumour cells loos polarity, we have developed cutting-edge, high-content microscopy and computational image analysis of tumour spheroids and organoids, live-imaging how normal cells become tumours. Molecularly, we focus on two pathways: phosphoinositide signalling (including the kinases and phosphatases that produce them, and master regulatory of their function: the ARF GTPases ), and the role of the metastasis-promoting sialomucin, Podocalyxin. We are particularly interested in how these participate in metastasis.
Our ultimate aim is to investigate such changes in cell polarity as potential future biomarkers of cancer in patients, and possible targets for future therapeutic interventions.
Click here to read David's interview with the Journal of Cell Science.
Other funding:
pdf Bryant Lab Report (623 KB)
Nikolatou K, Sandilands E, Román-Fernández A, Cumming EM, Freckmann E, Lilla S, Buetow L, McGarry L, Neilson M, Shaw R, Strachan D, Miller C, Huang DT, McNeish IA, Norman JC, Zanivan S, Bryant DM. PTEN deficiency exposes a requirement for an ARF GTPase module for integrin-dependent invasion in ovarian cancer. The EMBO Journal. 2023;n/a:e113987.
Sandilands E, Freckmann EC, Cumming EM, Román-Fernández A, McGarry L, Anand J, Galbraith L, Mason S, Patel R, Nixon C, Cartwright J, Leung HY, Blyth K, Bryant DM. The small GTPase ARF3 controls invasion modality and metastasis by regulating N-cadherin levels. Journal of Cell Biology. 2023;222: e202206115
Román-Fernández A, Mansour MA, Kugeratski FG, Anand J, Sandilands E, Galbraith L, Rakovic K, Freckmann EC, Cumming EM, Park J, Nikolatou K, Lilla S, Shaw R, Strachan D, Mason S, Patel R, McGarry L, Katoch A, Campbell KJ, Nixon C, Miller CJ, Leung HY, Le Quesne J, Norman JC, Zanivan S, Blyth K, Bryant DM. Spatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function. Sci Adv. 2023;9:eabq1858.
Freckmann EC, Sandilands E, Cumming E, Neilson M, Román-Fernández A, Nikolatou K, Nacke M, Lannagan TRM, Hedley A, Strachan D, Salji M, Morton JP, McGarry L, Leung HY, Sansom OJ, Miller CJ, Bryant DM. Traject3d allows label-free identification of distinct co-occurring phenotypes within 3D culture by live imaging. Nat Commun. 2022;13:5317.
Nacke M, Sandilands E, Nikolatou K, Román-Fernández Á, Mason S, Patel R, Lilla S, Yelland T, Galbraith LCA, Freckmann EC, McGarry L, Morton JP, Shanks E, Leung HY, Markert E, Ismail S, Zanivan S, Blyth K, Bryant DM. An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism. Nat Commun. 2021;12:1623.
2006: PhD, University of Queensland, Australia, Supervisor Jennifer Stow
2002: BSc (Hons) Class I, University of Queensland, Australia
2022-present: Reader, School of Cancer Sciences, University of Glasgow
2014-present: Beatson Associate, CRUK Scotland Institute
2014-2022: Senior Lecturer, School of Cancer Sciences, University of Glasgow
2012-2014: Associate Academic Researcher, University of California, San Francisco, USA
2006-2012: Postdoctoral Fellow with Keith Mostov, UC San Francisco, USA
2022-present: Editor, Journal of Cell Science
2019-present: Editorial Advisory Board, Journal of Cell Science
2019-present: Deputy Chair, Athena Swan Committee, School of Cancer Sciences
2017-present: Affiliate Member, BioRxiv Biology Preprint Server
2015-present: Editorial Board Member, International Review of Cell and Molecular Biology
2018 Profiled as 'Cell Scientist to watch', Journal of Cell Science
2011 Finalist, U. Queensland 'Young Alumnus of the Year' Award
2007 Postdoctoral Fellowship, Susan G. Komen Breast Cancer Foundation
2005 Cure Cancer Foundation 'Australian Young Researcher of the Year'
Nikolatou K, Sandilands E, Román-Fernández A, Cumming EM, Freckmann E, Lilla S, Buetow L, McGarry L, Neilson M, Shaw R, Strachan D, Miller C, Huang DT, McNeish IA, Norman JC, Zanivan S, Bryant DM. PTEN deficiency exposes a requirement for an ARF GTPase module for integrin-dependent invasion in ovarian cancer. The EMBO Journal. 2023;n/a:e113987.
Román-Fernández A, Mansour MA, Kugeratski FG, Anand J, Sandilands E, Galbraith L, Rakovic K, Freckmann EC, Cumming EM, Park J, Nikolatou K, Lilla S, Shaw R, Strachan D, Mason S, Patel R, McGarry L, Katoch A, Campbell KJ, Nixon C, Miller CJ, Leung HY, Le Quesne J, Norman JC, Zanivan S, Blyth K, Bryant DM. Spatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function. Sci Adv. 2023;9:eabq1858.
Sandilands E, Freckmann EC, Cumming EM, Román-Fernández A, McGarry L, Anand J, Galbraith L, Mason S, Patel R, Nixon C, Cartwright J, Leung HY, Blyth K, Bryant DM. The small GTPase ARF3 controls invasion modality and metastasis by regulating N-cadherin levels. Journal of Cell Biology. 2023;222: e202206115
Bryant DM. We are the system. J Cell Sci. 2023(24).
Nikolatou K, Bryant DM, Sandilands E. The ARF GTPase regulatory network in collective invasion and metastasis. Biochem Soc Trans. 2023.
Freckmann EC, Sandilands E, Cumming E, Neilson M, Román-Fernández A, Nikolatou K, Nacke M, Lannagan TRM, Hedley A, Strachan D, Salji M, Morton JP, McGarry L, Leung HY, Sansom OJ, Miller CJ, Bryant DM. Traject3d allows label-free identification of distinct co-occurring phenotypes within 3D culture by live imaging. Nat Commun. 2022;13:5317.
Kai F, Ou G, Tourdot RW, Stashko C, Gaietta G, Swift MF, Volkmann N, Long AF, Han Y, Huang HH, Northey JJ, Leidal AM, Viasnoff V, Bryant DM, Guo W, Wiita AP, Guo M, Dumont S, Hanein D, Radhakrishnan R, Weaver VM. ECM dimensionality tunes actin tension to modulate endoplasmic reticulum function and spheroid phenotypes of mammary epithelial cells. Embo j. 2022; 41:e109205
Nikolatou K, Sandilands E, Roman-Fernandez A, Cumming EM, Freckmann EC, Lilla S, Buetow L, McGarry L, Neilson M, Shaw R, Strachan D, Miller C, Huang DT, McNeish IA, Norman JC, Zanivan S, Bryant D. PTEN deficiency exposes a requirement for an ARF GTPase module in integrin-dependent invasion in ovarian cancer. bioRxiv. 2022;Volume:2022.2011.2029.518198.
Román-Fernández Á, Sandilands E, Bryant DM. The Use of Three-Dimensional Cell Culture to Study Apicobasal Polarization and Lumen Formation. Methods Mol Biol. 2022;2438:439-454.
Bristow RG, Engel J, Jayasinghe I, Kampmann M, James Sansom O, Bryant DM. Conversations with LGBT+ scientists about visibility, leadership and climbing the career ladder. Journal of Cell Science. 2022;135:jcs259880
Nacke M, Sandilands E, Nikolatou K, Román-Fernández Á, Mason S, Patel R, Lilla S, Yelland T, Galbraith LCA, Freckmann EC, McGarry L, Morton JP, Shanks E, Leung HY, Markert E, Ismail S, Zanivan S, Blyth K, Bryant DM. An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism. Nat Commun. 2021;12:1623.
Nászai M, Bellec K, Yu Y, Román-Fernández A, Sandilands E, Johansson J, Campbell AD, Norman JC, Sansom OJ, Bryant DM, Cordero JB. RAL GTPases mediate EGFR-driven intestinal stem cell proliferation and tumourigenesis. Elife. 2021;10:e63807
Millar R, Kilbey A, Remak SJ, Severson TM, Dhayade S, Sandilands E, Foster K, Bryant DM, Blyth K, Coffelt SB. The MSP-RON axis stimulates cancer cell growth in models of triple negative breast cancer. Molecular oncology. 2020;14: 1868-1880
Kugeratski FG, Atkinson SJ, Neilson LJ, Lilla S, Knight JRP, Serneels J, Juin A, Ismail S, Bryant DM, Markert EK, Machesky LM, Mazzone M, Sansom OJ, Zanivan S. Hypoxic cancer-associated fibroblasts increase NCBP2-AS2/HIAR to promote endothelial sprouting through enhanced VEGF signaling. Science signaling 2019; 12: eaan8247
Fort L, Batista JM, Thomason PA, Spence HJ, Whitelaw JA, Tweedy L, Greaves J, Martin KJ, Anderson KI, Brown P, Lilla S, Neilson MP, Tafelmeyer P, Zanivan S, Ismail S, Bryant DM, Tomkinson NCO, Chamberlain LH, Mastick GS, Insall RH, Machesky LM. Fam49/CYRI interacts with Rac1 and locally suppresses protrusions. Nat Cell Biol. 2018; 20: 1159-71
Hewit K, Sandilands E, Martinez RS, James D, Leung HY, Bryant DM, Shanks E, Markert EK. A functional genomics screen reveals a strong synergistic effect between docetaxel and the mitotic gene DLGAP5 that is mediated by the androgen receptor. Cell Death Dis. 2018; 9: 1069.
Roman-Fernandez A, Roignot J, Sandilands E, Nacke M, Mansour MA, McGarry L, Shanks E, Mostov KE, Bryant DM. The phospholipid PI(3,4)P2 is an apical identity determinant. Nat Commun. 2018; 9: 5041.
Stehbens SJ, Ju RJ, Adams MN, Perry S, Haass NK, Bryant DM, Pollock PM. FGFR2b activating mutations disrupt cell polarity to potentiate migration and invasion in endometrial cancer. J Cell Sci 2018; 131:
Datta A, Sandilands E, Mostov KE, Bryant DM. Fibroblast-derived HGF drives acinar lung cancer cell polarization through integrin-dependent RhoA-ROCK1 inhibition. Cell Signal 2017; 40: 91-8
Gao L, Yang Z, Hiremath C, Zimmerman SE, Long B, Brakeman PR, Mostov KE, Bryant DM, Luby-Phelps K, Marciano DK. Afadin orients cell division to position the tubule lumen in developing renal tubules. Development 2017; 144: 3511-20
Reid SE, Kay EJ, Neilson LJ, Henze AT, Serneels J, McGhee EJ, Dhayade S, Nixon C, Mackey JB, Santi A, Swaminathan K, Athineos D, Papalazarou V, Patella F, Roman-Fernandez A, ElMaghloob Y, Hernandez-Fernaud JR, Adams RH, Ismail S, Bryant DM et al. Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium. EMBO J 2017; 36: 2373-89
Ruch TR, Bryant DM, Mostov KE, Engel JN. Par3 integrates Tiam1 and phosphatidylinositol 3-kinase signaling to change apical membrane identity. Mol Biol Cell 2017; 28: 252-60
Bryant D, Johnson A. Meeting report - Intercellular interactions in context: towards a mechanistic understanding of cells in organs. J Cell Sci 2017; 130: 2083-85
Yang Z, Zimmerman SE, Tsunezumi J, Braitsch C, Trent C, Bryant DM, Cleaver O, Gonzalez-Manchon C, Marciano DK. Role of CD34 family members in lumen formation in the developing kidney. Dev Biol. 2016; 418: 66-74
Bryant DM, Yap AS. Editorial overview: Membrane traffic and cell polarity. Traffic. 2016; 17: 1231-2
Roman-Fernandez A, Bryant DM. Complex polarity: Building multicellular tissues through apical membrane traffic. Traffic. 2016; 17: 1244-61,
Dr Archana Katoch (UKRI Future Leader Fellowship)
Dr Emma Sandilands (University of Glasgow)
Ms Amy Bryson (University of Glasgow)
Dr Mohammed Mansour, Postdoctoral Fellow (Now: Senior Lecturer, London Southbank University)
Dr Narissa Parry, PhD Student (rotation)
Dr Marisa Nacke, PhD Student
Dr Alvaro Roman Fernandez, Postdoctoral Fellow (Now: ThermoFisher)
Dr Konstantina Nikolatou, PhD Student (Now: Postdoctoral Fellow, Francis Crick Institute)
Dr Eva Freckmann, PhD Student (Now: Postdoctoral Fellow, CRUK Scotland Institute)
Dr Erin Cumming PhD Student (Now: Postdoctoral Fellow, CRUK Scotland Institute)
Understanding how cancer spreads from its primary site of origin to distant organs is one of the major challenges in cancer research. What has become evident in recent years is that mutations in cancer cells are not sufficient to drive metastasis formation – cancer cells need assistance from surrounding healthy cells. Among these various healthy cells, immune cells have emerged as powerful instigators of metastasis formation but, at the same time, immune cells can also prevent cancer cells from spreading.
Our lab focuses on these dichotomous roles of immune cells and how tumours control immune cell behaviour. We study these concepts in the context of breast, pancreatic and colorectal cancers. We are particularly interested in γδ T cells, a rare population of T cells with properties that are distinct from conventional CD4 and CD8 T cells, as γδ T cells can be both pro-tumourigenic and anti-tumourigenic. Our ultimate goal is to understand how γδ T cells and other immune cells participate in the metastatic process and to develop new immunotherapies that counteract metastatic lesions.
Find out more about Seth's recent research in this article by STV News here.
Read the story from the Evening Times here.
Read about Seth's background and move to Glasgow here.
pdf Coffelt Lab Report (84 KB)
Coffelt SB, Wellenstein MD, de Visser KE. Neutrophils in cancer: neutral no more. Nat Rev Cancer. 2016; 16: 431–446
Coffelt SB, Kersten K, Doornebal CW, Weiden J, Vrijland K, Hau CS, Verstegen NJ, Ciampricotti M, Hawinkels LJ, Jonkers J, de Visser KE. IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature. 2015; 522: 345-8.
Coffelt SB, de Visser KE. Cancer: Inflammation lights the way to metastasis. Nature. 2014; 507: 48-9.
Al-ofi E, Coffelt SB*, Anumba DO*. Monocyte subpopulations from pre-eclamptic patients are abnormally skewed and exhibit exaggerated responses to Toll-like receptor ligands. PLoS One. 2012; 7: e42217. *co-senior author
Coffelt SB, Chen YY, Muthana M, Welford AF, Tal AO, Scholz A, Plate KH, Reiss Y, Murdoch C, De Palma M, Lewis CE. Angiopoietin 2 stimulates TIE2-expressing monocytes to suppress T cell activation and to promote regulatory T cell expansion. J Immunol. 2011; 186: 4183-90.
Coffelt SB*, Tomchuck SL, Zwezdaryk KJ, Danka ES, Scandurro AB. Leucine leucine-37 uses formyl peptide receptor-like 1 to activate signal transduction pathways, stimulate oncogenic gene expression, and enhance the invasiveness of ovarian cancer cells. Mol Cancer Res. 2009; 7: 907-15. *corresponding author
2006: PhD, Interdisciplinary Program in Molecular & Cellular Biology, Tulane University, USA
2000: BA, Biology & Chemistry, Minors in Music & Global Studies, Drury University, USA
2023-present: Professor, School of Cancer Sciences, University of Glasgow
2016-present: Senior Research Fellow/Beatson Associate, University of Glasgow
2011-2016: Marie Curie Postdoctoral Fellow with Karin de Visser, The Netherlands Cancer Institute, The Netherlands
2008-2011: Postdoctoral Research Associate with Claire Lewis, University of Sheffield, UK
2007-2008: Postdoctoral Fellow with Aline Scandurro, Tulane University, USA
2005-2007: Visiting Scientist with Frank Marini & Michael Andreeff, MD Anderson Cancer Center, USA
2005: Adjunct Professor, Drury University, USA
British Association for Cancer Research AstraZeneca Young Scientist Frank Rose Award, 2018
Wellcome Trust Seed Award, 2017
Outstanding Staff Member Award, Netherlands Cancer Institute, 2014
Scholar-in-Training Award, AACR Special Conference on Advances in Breast Cancer Research, 2013
Netherlands Cancer Institute Staff Evening Presenter, 2013
Marie Curie Intra-European Fellowship for Career Development, 2011-2013
Exceptional Contribution Award, University of Sheffield, 2010
Top 10 Finalist for MedImmune's Oncology Research Abstract Competition, 2009
Cancer Association of Greater New Orleans' Student Grant, 2005
Breast Cancer Now Grants Committee member
Dawson A, Zarou MM, Prasad B, Bittencourt-Silvestre J, Zerbst D, Himonas E, Hsieh YC, van Loon I, Blanco GR, Ianniciello A, Kerekes Z, Krishnan V, Agarwal P, Almasoudi H, McCluskey L, Hopcroft LEM, Scott MT, Baquero P, Dunn K, Vetrie D, Copland M, Bhatia R, Coffelt SB, Tiong OS, Wheadon H, Zanivan S, Kirschner K, Helgason GV. Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche. Nat Commun. 2024;15(1):1090.
Fercoq F, Cairns GS, Donatis MD, Mackey JBG, Floerchinger A, McFarlane A, Raffo-Iraolagoitia XL, Whyte D, Arnott LWG, Nixon C, Wiesheu R, Kilbey A, Brown L, Al-Khalidi S, Norman JC, Roberts EW, Blyth K, Coffelt SB, Carlin LM. Integrin inactivation slows down neutrophils congesting the pre-metastatic lung in a model of breast cancer. bioRxiv. 2024:2024.2003.2019.585724.
Whyte D, Voorde JV, Sumpton D, Dhayade S, Dornier E, Moore M, Novo D, Peters J, Wiesheu R, Mackey JBG, McFarlane AJ, Fercoq F, Fisher S, Caballero CD, Gilroy K, Redmond KL, Mitchell LE, Anderson E, Thomson G, Dzierozynski LN, Saab JJA, Lewis CA, Muir A, Halbrook CJ, Strathdee D, Jackstadt R, Nixon C, Dunne P, Steele CW, Carlin LM, Macpherson IR, Roberts EW, Coffelt SB, Blyth K, Sansom OJ, Norman JC, Clarke CJ. Uridine Phosphorylase-1 supports metastasis of mammary cancer by altering immune and extracellular matrix landscapes of the lung. bioRxiv. 2024:2024.2007.2002.601676.
Wiesheu R, Edwards SC, Hedley A, Hall H, Tosolini M, Fares da Silva MGF, Sumaria N, Castenmiller SM, Wardak L, Optaczy Y, Lynn A, Hill DG, Hayes AJ, Hay J, Kilbey A, Shaw R, Whyte D, Walsh PJ, Michie AM, Graham GJ, Manoharan A, Halsey C, Blyth K, Wolkers MC, Miller C, Pennington DJ, Jones GW, Fournie JJ, Bekiaris V, Coffelt SB. IL-27 maintains cytotoxic Ly6C(+) γδ T cells that arise from immature precursors. Embo j. 2024.
Lupo F, Coffelt SB. Stressed out neutrophils drive metastasis. Immunity. 2024(4):840-842.
Edwards SC, Hedley A, Hoevenaar WHM, Wiesheu R, Glauner T, Kilbey A, Shaw R, Boufea K, Batada N, Hatano S, Yoshikai Y, Blyth K, Miller C, Kirschner K, Coffelt SB. PD-1 and TIM-3 differentially regulate subsets of mouse IL-17A-producing γδ T cells. J Exp Med. 2023;220.:e20211431
Laing S, Kruspig B, Shaw R, Officer-Jones L, Edwards S, McKinven D, Hsieh Y-C, Powley I, Brady N, Pennie R, Kwan R, Lima A, Myrta S, Periyasamy M, Dye IC, Nixon C, Clark G, Junttila MR, Maddalo D, Miller C, Ali S, Fuchter MJ, Nickles D, Kirschner K, Brown RB, Quesne JL, Strathdee D, Coffelt SB, Roberts E, Murphy DJ. ERBB signalling contributes to immune evasion in KRAS-driven lung adenocarcinoma. bioRxiv. 2023:2023.2007.2024.550274.
Suzuki T, Kilbey A, Casa Rodriguez N, Lawlor A, Georgakopoulou A, Hayman H, Yin Swe KL, Nordin A, Cantù C, Vantourout P, Ridgway RA, Byrne RM, Chen L, Verzi MP, Gay DM, Gil Vazquez E, Belnoue-Davis HL, Gilroy K, Kostner AH, Kersten C, Thuwajit C, Andersen DK, Wiesheu R, Jandke A, Blyth K, Roseweir AK, Leedham SJ, Dunne PD, Edwards J, Hayday A, Sansom OJ, Coffelt SB. β-catenin drives butyrophilin-like molecule loss and γδ T-cell exclusion in colon cancer. Cancer Immunology Research. 2023;11: 1137-1155
Quintana JF, Sinton MC, Chandrasegaran P, Lestari AN, Heslop R, Cheaib B, Ogunsola J, Ngoyi DM, Kuispond Swar NR, Cooper A, Mabbott NA, Coffelt SB, MacLeod A. γδ T cells control murine skin inflammation and subcutaneous adipose wasting during chronic Trypanosoma brucei infection. Nat Commun. 2023;14(1):5279.
Raffo-Iraolagoitia XL, McFarlane AJ, Kruspig B, Fercoq F, Secklehner J, Donatis MD, Mackey JBG, Wiesheu R, Laing S, Hsieh Y-C, Shaw R, Corbyn R, Nixon C, Miller C, Kirschner K, Bain CC, Daniel J. Murphy, Seth B. Coffelt, Carlin LM. γδ T cells impair airway macrophage differentiation in lung adenocarcinoma. bioRxiv. 2023:2023.2009.2014.557344.
Waldron JA, Kanellos G, Smith RCL, Knight JRP, Munro J, Alexandrou C, Vlahov N, Pardo-Fernandez L, Moore M, Gillen SL, Strathdee D, Stevenson D, Warrander FC, Gilroy K, Nixon C, Cadden B, Powley I, Officer-Jones L, Ballantyne F, Hay J, Pennel K, Edwards J, Campbell AD, Ridgway RA, Coffelt SB, Norman J, Quesne JL, Bushell M, Sansom OJ. eIF4A1 is essential for reprogramming the translational landscape of Wnt-driven colorectal cancers. bioRxiv. 2023:2023.2011.2010.566546.
Coffelt SB, Morton JP. LOXL2 in pancreatic tumourigenesis: the complexity of tumour-stromal crosstalk exemplified. Gut. 2023;72:221-222.
Coffelt SB, Suzuki T. The two sides of the γδ T cell coin. Nat Cancer. 2023;10.1038/s43018-023-00587-y.
Coffelt SB, Suzuki T. γδ T cells turn the tables on immune-evasive colon cancer. Med. 2023;4:141-142.
Curio S, Edwards SC, Suzuki T, McGovern J, Triulzi C, Yoshida N, Jonsson G, Glauner T, Rami D, Wiesheu R, Kilbey A, Purcell RV, Coffelt SB, Guerra N. NKG2D signaling regulates IL-17A-producing γδT cells in mice to promote cancer progression. Discovery Immunology. 2022;1:kyac002.
Paterson K, Paterson S, Mulholland T, Coffelt SB, Zagnoni M. Assessment of CAR-T Cell-Mediated Cytotoxicity in 3D Microfluidic Cancer Co-Culture Models for Combination Therapy. IEEE Open J Eng Med Biol. 2022;3:86-95.
van Wagensveld L, van Baal J, Timmermans M, Gaillard D, Borghuis L, Coffelt SB, Rosenberg EH, Lok CAR, Nijman HW, Kooreman LFS, Sanders J, de Bruijn M, Wessels LFA, van der Wiel R, Rausch C, Broeks A, Kruitwagen R, van der Aa MA, Sonke GS, Schouten PC, Van de Vijver KK, Horlings HM. Homologous Recombination Deficiency and Cyclin E1 Amplification Are Correlated with Immune Cell Infiltration and Survival in High-Grade Serous Ovarian Cancer. Cancers (Basel). 2022;14.
Lawrence M, Wiesheu R, Coffelt SB. The duplexity of unconventional T cells in cancer. The International Journal of Biochemistry & Cell Biology. 2022;146:106213.
Edwards SC, Hedley A, Hoevenaar WHM, Glauner T, Wiesheu R, Kilbey A, Shaw R, Boufea K, Batada N, Blyth K, Miller C, Kirschner K, Coffelt SB. Single-cell analysis uncovers differential regulation of lung γδ T cell subsets by the co-inhibitory molecules, PD-1 and TIM-3. bioRxiv. 2021.
Johnson SA, Ormsby MJ, Wessel HM, Hulme HE, Bravo-Blas A, McIntosh A, Mason S, Coffelt SB, Tait SWG, Mowat AM, Milling SWF, Blyth K, Wall DM. Monocytes mediate Salmonella Typhimurium-induced tumour growth inhibition in a mouse melanoma model. Eur J Immunol. 2021;14:5965
Paterson K, Zanivan S, Glasspool R, Coffelt SB, Zagnoni M. Microfluidic technologies for immunotherapy studies on solid tumours. Lab Chip. 2021;21:2306-2329.
Edwards SC, Hoevenaar WHM, Coffelt SB. Emerging immunotherapies for metastasis. Br J Cancer. 2021;124:37-48.
McFarlane AJ, Fercoq F, Coffelt SB, Carlin LM. Neutrophil dynamics in the tumor microenvironment. J Clin Invest. 2021;131: ed2021.
Dhayade S, Pietzke M, Wiesheu R, Tait-Mulder J, Athineos D, Sumpton D, Coffelt S, Blyth K, Vazquez A. Impact of Formate Supplementation on Body Weight and Plasma Amino Acids. Nutrients. 2020; 12(8):2181.
Millar R, Kilbey A, Remak SJ, Severson TM, Dhayade S, Sandilands E, Foster K, Bryant DM, Blyth K, Coffelt SB. The MSP-RON axis stimulates cancer cell growth in models of triple negative breast cancer. Molecular oncology. 2020;14: 1868-1880
Muthalagu N, Monteverde T, Raffo-Iraolagoitia X, Wiesheu R, Whyte D, Hedley A, Laing S, Kruspig B, Upstill-Goddard R, Shaw R, Neidler S, Rink C, Karim SA, Gyuraszova K, Nixon C, Clark W, Biankin AV, Carlin LM, Coffelt SB, Sansom OJ, Morton JP, Murphy DJ. Repression of the Type I Interferon pathway underlies MYC & KRAS-dependent evasion of NK & B cells in Pancreatic Ductal Adenocarcinoma. Cancer discovery. 2020;
Boire A, Coffelt SB, Quezada SA, Vander Heiden MG, Weeraratna AT. Tumour Dormancy and Reawakening: Opportunities and Challenges. Trends in cancer. 2019; 5: 762-765.
Mackey JBG, Coffelt SB, Carlin LM. Neutrophil Maturity in Cancer. Frontiers in immunology. 2019; 10: 1912.
Salvagno C, Ciampricotti M, Tuit S, Hau CS, van Weverwijk A, Coffelt SB, Kersten K, Vrijland K, Kos K, Ulas T, Song JY, Ooi CH, Ruttinger D, Cassier PA, Jonkers J, Schultze JL, Ries CH, de Visser KE. Therapeutic targeting of macrophages enhances chemotherapy efficacy by unleashing type I interferon response. Nat Cell Biol. 2019; 21: 511-21.
Silva-Santos B, Mensurado S, Coffelt SB. γδ T cells: pleiotropic immune effectors with therapeutic potential in cancer. Nature Reviews Cancer. 2019; 19, 392–404
Wellenstein MD, Coffelt SB, Duits DEM, van Miltenburg MH, Slagter M, de Rink I, Henneman L, Kas SM, Prekovic S, Hau CS, Vrijland K, Drenth AP, de Korte-Grimmerink R, Schut E, van der Heijden I, Zwart W, Wessels LFA, Schumacher TN, Jonkers J, de Visser KE. Loss of p53 triggers WNT-dependent systemic inflammation to drive breast cancer metastasis. Nature. 2019; 572: 538–542
Kruspig B, Monteverde T, Neidler S, Hock A, Kerr E, Nixon C, Clark W, Hedley A, Laing S, Coffelt SB, Le Quesne J, Dick C, Vousden K, Martins CP, Murphy DJ. The ERBB network facilitates KRAS-driven lung tumorigenesis. Sci Transl Med. 2018; 10: eaao2565
Carron EC, Homra S, Rosenberg J, Coffelt SB, Kittrell F, Zhang Y, Creighton CJ, Fuqua SA, Medina D, Machado HL. Macrophages promote the progression of premalignant mammary lesions to invasive cancer. Oncotarget 2017; 8: 50731-46
Kersten K, Coffelt SB, Hoogstraat M, Verstegen NJM, Vrijland K, Ciampricotti M, Doornebal CW, Hau CS, Wellenstein MD, Salvagno C, Doshi P, Lips EH, Wessels LFA, de Visser KE. Mammary tumor-derived CCL2 enhances pro-metastatic systemic inflammation through upregulation of IL1β in tumor-associated macrophages. Oncoimmunology 2017; 6:e1334744.
Rumney RMH, Coffelt SB, Neale TA, Dhayade S, Tozer GM, Miller G. PyMT-Maclow. A novel, inducible, murine model for determining the role of CD68 positive cells in breast tumor development. PLoS One 2017; 12: e0188591
van Baal J, Van de Vijver KK, Coffelt SB, van der Noort V, van Driel WJ, Kenter GG, Buist MR, Lok C. Incidence of lymph node metastases in clinical early-stage mucinous and seromucinous ovarian carcinoma: a retrospective cohort study. BJOG 2017; 124: 486-94
Walton JB, Farquharson M, Mason S, Port J, Kruspig B, Dowson S, Stevenson D, Murphy D, Matzuk M, Kim J, Coffelt S, Blyth K, McNeish IA. CRISPR/Cas9-derived models of ovarian high grade serous carcinoma targeting Brca1, Pten and Nf1, and correlation with platinum sensitivity. Sci Rep 2017; 7: 16827
Coffelt SB, de Visser KE. Revving up dendritic cells while braking PD-L1 to jump-start the cancer-immunity cycle motor. Immunity 2016; 44: 722-4
Coffelt SB, de Visser KE. Systemic inflammation: Cancer's long-distance reach to maximize metastasis. Oncoimmunology 2016; 5: e1075694
Coffelt SB, Wellenstein MD, de Visser KE. Neutrophils in cancer: Neutral no more. Nat Rev Cancer 2016; 16: 431-46
Rahat MA, Coffelt SB, Granot Z, Muthana M, Amedei A. Macrophages and neutrophils: Regulation of the inflammatory microenvironment in autoimmunity and cancer. Mediators Inflamm 2016; 2016: 5894347
Nadia Iqbal
Toshiyasu Suzuki (McNab)
Heather Spence (CRUK Career Establishment Award)
Anna Kilbey (CRUK Career Establishment Award)
Kyi Lai Yin Swe (Cancer Research Institute CLIP award)
Federico Lupo (CRUK Career Development Award)
Anna Pidoux
Elizabeth Thompson
Muhammad Aslam
Sarah Edwards (Senior Scientist, Takeda)
Kyla Foster (University of Colorado, Boulder, USA)
Anastasia Georgakopoulou
Teresa Glauner
Wilma Hoevenaar
Rhona Millar
Erin Morris (Department Chair of Biology & Chemistry, Baker University, Baldwin City, Kansas, USA)
Damiano Rami
Sarah Jane Remak
Josip Vrancic
Robert Wiesheu
Every year around 340,000 people die of pancreatic cancer worldwide, and by 2030 pancreatic cancer is predicted to be the second commonest cause of cancer death in the western world. Most patients present too late for surgery, with aggressive invasive or metastatic disease. Furthermore, current chemotherapies offer little benefit, so we urgently need to better understand the disease and identify better options for clinicians and patients.
To do this, we model different genetic subsets of the disease in genetically engineered models. These models mimic human tumours in terms of the genes altered, and also because they develop a dense desmoplastic stroma of fibroblasts, stellate cells, immune cells, and extracellular matrix proteins such as collagen.
By studying our models, we can determine the importance of specific genetic and transcriptomic changes identified in human tumours, identify novel targets for therapy, both in tumour cells and in the microenvironment, and test new therapies pre-clinically.
See the following CRUK blogs for more details about Prof Morton's work:
Other funding:
pdf Morton Lab Report (127 KB)
Steele CW, Karim SA, Leach JD, Bailey P, Upstill-Goddard R, Rishi L, Foth M, Bryson S, McDaid K, Wilson Z, Eberlein C, Candido JB, Clarke M, Nixon C, Connelly J, Jamieson N, Carter CR, Balkwill F, Chang DK, Evans TR, Strathdee D, Biankin AV, Nibbs RJ, Barry ST, Sansom OJ & Morton JP (2016) CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma. Cancer Cell. 29, 832-45.
Driscoll DR, Karim SA, Sano M, Gay DM, Jacob W, Yu J, Mizukami Y, Gopinathan A, Jodrell DI, Evans TR, Bardeesy N, Hall MN, Quattrochi BJ, Klimstra DS, Barry ST, Sansom OJ, Lewis BC & Morton JP (2016) mTORC2 Signaling Drives the Development and Progression of Pancreatic Cancer Cancer Res. 76, 6911-23.
Steele CW, Karim SA, Foth M, Rishi L, Leach JD, Porter RJ, Nixon C, Jeffry Evans TR, Carter CR, Nibbs RJ, Sansom OJ & Morton JP (2015) CXCR2 inhibition suppresses acute and chronic pancreatic inflammation. J Pathol. 237, 85-97.
Miller BW*, Morton JP*, Pinese M, Saturno G, Jamieson NB, McGhee E, Timpson P, Leach J, McGarry L, Shanks E, Bailey P, Chang D, Oien K, Karim S, Au A, Steele C, Carter CR, McKay C, Anderson K, Evans TR, Marais R, Springer C, Biankin A, Erler JT & Sansom OJ (2015) Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy. EMBO Mol Med. 7, 1063-76.
Morran DC, Wu J, Jamieson NB, Mrowinska A, Kalna G, Karim SA, Au AY, Scarlett CJ, Chang DK, Pajak MZ, Australian Pancreatic Cancer Genome I, Oien KA, McKay CJ, Carter CR, Gillen G, Champion S, Pimlott SL, Anderson KI, Evans TR, Grimmond SM, Biankin AV, Sansom OJ & Morton JP (2014) Targeting mTOR dependency in pancreatic cancer. Gut. 63, 1481-9.
2001: PhD, Veterinary Pathology, University of Glasgow
1998: BSc (Hons. 1st), Medical Biochemistry, University of Glasgow
2019-present: Professor, School of Cancer Sciences, University of Glasgow, Glasgow, UK
2019-present: Senior Staff Scientist, Cancer Research UK Scotland Institute, Glasgow, UK
2015-present: Preclinical trials coordinator, Cancer Research UK Glasgow Centre
2010-2019: Associate Scientist, Cancer Research UK Beatson Institute, Glasgow, UK
2007-2010: Postdoctoral Research Associate, Institute of Cancer Sciences, University of Glasgow, UK
2004-2007: Postdoctoral Research Fellow, University of Massachusetts Medical School, Worcester, USA
2001-2004: Postdoctoral Research Assistant, Institute of Biomedical & Life Sciences, University of Glasgow, UK
Astuti Y, Raymant M, Quaranta V, Clarke K, Abudula M, Smith O, Bellomo G, Chandran-Gorner V, Nourse C, Halloran C, Ghaneh P, Palmer D, Jones RP, Campbell F, Pollard JW, Morton JP, Mielgo A, Schmid MC. Efferocytosis reprograms the tumor microenvironment to promote pancreatic cancer liver metastasis. Nat Cancer. 2024.
Go S, Demetriou C, Valenzano G, Hughes S, Lanfredini S, Ferry H, Arbe-Barnes E, Sivakumar S, Bashford-Rogers R, Middleton MR, Mukherjee S, Morton J, Jones K, O’Neill E. Tissue-resident NK cells support survival in pancreatic cancer through promotion of cDC1-CD8T activity. bioRxiv. 2024:2023.2010.2014.562332.
Pereira BA, Ritchie S, Chambers CR, Gordon KA, Magenau A, Murphy KJ, Nobis M, Tyma VM, Liew YF, Lucas MC, Naeini MM, Barkauskas DS, Chacon-Fajardo D, Howell AE, Parker AL, Warren SC, Reed DA, Lee V, Metcalf XL, Lee YK, O'Regan LP, Zhu J, Trpceski M, Fontaine ARM, Stoehr J, Rouet R, Lin X, Chitty JL, Porazinski S, Wu SZ, Filipe EC, Cadell AL, Holliday H, Yang J, Papanicolaou M, Lyons RJ, Zaratzian A, Tayao M, Da Silva A, Vennin C, Yin J, Dew AB, McMillan PJ, Goldstein LD, Deveson IW, Croucher DR, Samuel MS, Sim HW, Batten M, Chantrill L, Grimmond SM, Gill AJ, Samra J, Jeffry Evans TR, Sasaki T, Phan TG, Swarbrick A, Sansom OJ, Morton JP, Pajic M, Parker BL, Herrmann D, Cox TR, Timpson P. Temporally resolved proteomics identifies nidogen-2 as a cotarget in pancreatic cancer that modulates fibrosis and therapy response. Sci Adv. 2024;10(27):eadl1197.
Raymant M, Astuti Y, Alvaro-Espinosa L, Green D, Quaranta V, Bellomo G, Glenn M, Chandran-Gorner V, Palmer DH, Halloran C, Ghaneh P, Henderson NC, Morton JP, Valiente M, Mielgo A, Schmid MC. Macrophage-fibroblast JAK/STAT dependent crosstalk promotes liver metastatic outgrowth in pancreatic cancer. Nat Commun. 2024;15(1):3593.
Salvador-Barbero B, Alatsatianos M, Morton JP, Sansom OJ, Hogan C. Oncogenic KRAS cells use Wnt signalling and cell dormancy to override homeostatic cell elimination mechanisms in adult pancreas. bioRxiv. 2024:2024.2002.2013.579930.
Tesson M, Stevenson K, Karim SA, Nixon C, Chalmers AJ, Sansom OJ, O'Neil E, Jones K, Morton JP. Targeted irradiation in an autochthonous mouse model of pancreatic cancer. Dis Model Mech. 2024.
Tesson M, Morton JP. The preclinical gap in pancreatic cancer and radiotherapy. Dis Model Mech. 2024(7).
Coetzee AS, Carter EP, Rodríguez-Fernández L, Heward J, Wang Q, Karim SA, Boughetane L, Milton C, Uyulur F, Morton JP, Kocher HM, Grose RP. Nuclear FGFR1 promotes pancreatic stellate cell-driven invasion through up-regulation of Neuregulin 1. Oncogene. 2023; 42: 491-500
Conway JRW, Warren SC, Lee YK, McCulloch AT, Magenau A, Lee V, Metcalf XL, Stoehr J, Haigh K, Abdulkhalek L, Guaman CS, Reed DA, Murphy KJ, Pereira BA, Mélénec P, Chambers C, Latham SL, Lenthall H, Deenick EK, Ma Y, Phan T, Lim E, Joshua AM, Walters S, Grey ST, Shi YC, Zhang L, Herzog H, Croucher DR, Philp A, Scheele C, Herrmann D, Sansom OJ, Morton JP, Papa A, Haigh JJ, Nobis M, Timpson P. Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse. Sci Adv. 2023;9:eadf9063.
Fey SK, Najumudeen AK, Ford C, Gilroy K, Upstill-Goddard R, Chang DK, Clark W, Nixon C, Barry ST, Morton JP, Campbell AD, Sansom OJ. Kras loss of heterozygosity promotes MAPK dependent pancreatic ductal adenocarcinoma and induces therapeutic sensitivity. bioRxiv. 2023:2023.2008.2029.552598.
Go S, Demetriou C, Hughes S, Lanfredini S, Valenzano G, Ferry H, Arbe-Barnes E, Sivakumar S, Bashford-Rogers R, Middleton MR, Mukherjee S, Morton J, Jones K, O’Neill E. Tissue-resident NK cells support survival in pancreatic cancer through promotion of cDC1-CD8T activity. bioRxiv. 2023:2023.2010.2014.562332.
Graziano V, Dannhorn A, Hulme H, Williamson K, Buckley H, Karim SA, Wilson M, Lee SY, Kaistha BP, Islam S, Thaventhiran JED, Richards FM, Goodwin R, Brais R, Morton JP, Dovedi SJ, Schuller AG, Eyles J, Jodrell DI. Defining the spatial distribution of extracellular adenosine revealed a myeloid-dependent immunosuppressive microenvironment in pancreatic ductal adenocarcinoma. J Immunother Cancer. 2023;11.
Najumudeen AK, Fey SK, Millett LM, Ford C, Gilroy K, Gunduz N, Ridgway RA, Anderson E, Strathdee D, Clark W, Nixon C, Morton JP, Campbell AD, Sansom OJ. KRAS allelic imbalance drives tumour initiation yet suppresses metastasis in colorectal cancer in vivo. bioRxiv. 2023:2023.2008.2029.555396.
Perurena N, Lock R, Davis RA, Raghavan S, Pilla NF, Ng R, Loi P, Guild CJ, Miller AL, Sicinska E, Cleary JM, Rubinson DA, Wolpin BM, Gray NS, Santagata S, Hahn WC, Morton JP, Sansom OJ, Aguirre AJ, Cichowski K. USP9X mediates an acute adaptive response to MAPK suppression in pancreatic cancer but creates multiple actionable therapeutic vulnerabilities. Cell Rep Med. 2023;10.1016/j.xcrm.2023.101007:101007.
Whyte D, Skalka G, Walsh P, Wilczynska A, Paul NR, Mitchell C, Nixon C, Clarke W, Bushell M, Morton JP, Murphy DJ, Muthalagu N. NUAK1 governs centrosome replication in pancreatic cancer via MYPT1/PP1β and GSK3β-dependent regulation of PLK4. Mol Oncol. 2023;17:1212-1227
Barry ST, Gabrilovich DI, Sansom OJ, Campbell AD, Morton JP. Therapeutic targeting of tumour myeloid cells. Nat Rev Cancer. 2023; 23: 216–237
Coffelt SB, Morton JP. LOXL2 in pancreatic tumourigenesis: the complexity of tumour-stromal crosstalk exemplified. Gut. 2023;72:221-222.
Ali A, Jamieson NB, Khan IN, Chang D, Giovannetti E, Funel N, Frampton AE, Morton J, Sansom O, Evans TRJ, Duthie F, McKay CJ, Samra J, Gill AJ, Biankin A, Oien KA. Prognostic implications of microRNA-21 overexpression in pancreatic ductal adenocarcinoma: an international multicenter study of 686 patients. Am J Cancer Res. 2022;12:5668-5683.
Bellomo G, Rainer C, Quaranta V, Astuti Y, Raymant M, Boyd E, Stafferton R, Campbell F, Ghaneh P, Halloran CM, Hammond DE, Morton JP, Palmer D, Vimalachandran D, Jones R, Mielgo A, Schmid MC. Chemotherapy-induced infiltration of neutrophils promotes pancreatic cancer metastasis via Gas6/AXL signalling axis. Gut. 2022;
Below CR, Kelly J, Brown A, Humphries JD, Hutton C, Xu J, Lee BY, Cintas C, Zhang X, Hernandez-Gordillo V, Stockdale L, Goldsworthy MA, Geraghty J, Foster L, O'Reilly DA, Schedding B, Askari J, Burns J, Hodson N, Smith DL, Lally C, Ashton G, Knight D, Mironov A, Banyard A, Eble JA, Morton JP, Humphries MJ, Griffith LG, Jørgensen C. A microenvironment-inspired synthetic three-dimensional model for pancreatic ductal adenocarcinoma organoids. Nat Mater. 2022;21:110-119.
Freckmann EC, Sandilands E, Cumming E, Neilson M, Román-Fernández A, Nikolatou K, Nacke M, Lannagan TRM, Hedley A, Strachan D, Salji M, Morton JP, McGarry L, Leung HY, Sansom OJ, Miller CJ, Bryant DM. Traject3d allows label-free identification of distinct co-occurring phenotypes within 3D culture by live imaging. Nat Commun. 2022;13:5317.
Halbrook CJ, Thurston G, Boyer S, Anaraki C, Jiménez JA, McCarthy A, Steele NG, Kerk SA, Hong HS, Lin L, Law FV, Felton C, Scipioni L, Sajjakulnukit P, Andren A, Beutel AK, Singh R, Nelson BS, Van Den Bergh F, Krall AS, Mullen PJ, Zhang L, Batra S, Morton JP, Stanger BZ, Christofk HR, Digman MA, Beard DA, Viale A, Zhang J, Crawford HC, Pasca di Magliano M, Jorgensen C, Lyssiotis CA. Differential integrated stress response and asparagine production drive symbiosis and therapy resistance of pancreatic adenocarcinoma cells. Nat Cancer. 2022;3:1386-1403.
Kidger AM, Saville MK, Rushworth LK, Davidson J, Stellzig J, Ono M, Kuebelsbeck LA, Janssen KP, Holzmann B, Morton JP, Sansom OJ, Caunt CJ, Keyse SM. Suppression of mutant Kirsten-RAS (KRAS(G12D))-driven pancreatic carcinogenesis by dual-specificity MAP kinase phosphatases 5 and 6. Oncogene. 2022;41:2811–2823
Vaziri-Gohar A, Cassel J, Mohammed FS, Zarei M, Hue JJ, Hajihassani O, Graor HJ, Srikanth YVV, Karim SA, Abbas A, Prendergast E, Chen V, Katayama ES, Dukleska K, Khokhar I, Andren A, Zhang L, Wu C, Erokwu B, Flask CA, Zarei M, Wang R, Rothermel LD, Romani AMP, Bowers J, Getts R, Tatsuoka C, Morton JP, Bederman I, Brunengraber H, Lyssiotis CA, Salvino JM, Brody JR, Winter JM. Limited nutrient availability in the tumor microenvironment renders pancreatic tumors sensitive to allosteric IDH1 inhibitors. Nat Cancer. 2022;3:852-865.
Below CR, Kelly J, Brown A, Humphries JD, Hutton C, Xu J, Lee BY, Cintas C, Zhang X, Hernandez-Gordillo V, Stockdale L, Goldsworthy MA, Geraghty J, Foster L, O'Reilly DA, Schedding B, Askari J, Burns J, Hodson N, Smith DL, Lally C, Ashton G, Knight D, Mironov A, Banyard A, Eble JA, Morton JP, Humphries MJ, Griffith LG, Jørgensen C. A microenvironment-inspired synthetic three-dimensional model for pancreatic ductal adenocarcinoma organoids. Nat Mater. 2021;21:110–119
Dreyer SB, Upstill-Goddard R, Paulus-Hock V, Paris C, Lampraki E-M, Dray E, Serrels B, Caligiuri G, Rebus S, Plenker D, Galluzzo Z, Brunton H, Cunningham R, Tesson M, Nourse C, Bailey U-M, Jones M, Moran-Jones K, Wright DW, Duthie F, Oien K, Evers L, McKay CJ, McGregor GA, Gulati A, Brough R, Bajrami I, Pettitt S, Dziubinski ML, Candido J, Balkwill F, Barry ST, Grützmann R, Rahib L, Johns A, Pajic M, Froeling FEM, Beer P, Musgrove EA, Petersen GM, Ashworth A, Frame MC, Crawford HC, Simeone DM, Lord C, Mukhopadhyay D, Pilarsky C, Tuveson DA, Cooke SL, Jamieson NB, Morton JP, Sansom OJ, Bailey PJ, Biankin AV, Chang DK. Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer. Gastroenterology. 2021; 160:362-377
Falcomata C, Barthel S, Ulrich A, Diersch S, Veltkamp C, Rad L, Boniolo F, Solar M, Steiger K, Seidler B, Zukowska M, Madej J, Wang M, Ollinger R, Maresch R, Barenboim M, Eser S, Tschurtschenthaler M, Mehrabi A, Roessler S, Goeppert B, Kind A, Schnieke A, Robles MS, Bradley A, Schmid RM, Schmidt-Supprian M, Reichert M, Weichert W, Sansom OJ, Morton JP, Rad R, Schneider G, Saur D. Genetic screens identify a context-specific PI3K/p27Kip1 node driving extrahepatic biliary cancer. Cancer Discov. 2021;11: 3158–3177
Floerchinger A, Murphy KJ, Latham SL, Warren SC, McCulloch AT, Lee YK, Stoehr J, Mélénec P, Guaman CS, Metcalf XL, Lee V, Zaratzian A, Da Silva A, Tayao M, Rolo S, Phimmachanh M, Sultani G, McDonald L, Mason SM, Ferrari N, Ooms LM, Johnsson AE, Spence HJ, Olson MF, Machesky LM, Sansom OJ, Morton JP, Mitchell CA, Samuel MS, Croucher DR, Welch HCE, Blyth K, Caldon CE, Herrmann D, Anderson KI, Timpson P, Nobis M. Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: Guidance using optical window intravital FRET imaging. Cell Rep. 2021;36(11):109689.
Hill W, Zaragkoulias A, Salvador-Barbero B, Parfitt GJ, Alatsatianos M, Padilha A, Porazinski S, Woolley TE, Morton JP, Sansom OJ, Hogan C. EPHA2-dependent outcompetition of KRASG12D mutant cells by wild-type neighbors in the adult pancreas. Curr Biol. 2021;31:2550-2560
Hutton C, Heider F, Blanco-Gomez A, Banyard A, Kononov A, Zhang X, Karim S, Paulus-Hock V, Watt D, Steele N, Kemp S, Hogg EKJ, Kelly J, Jackstadt RF, Lopes F, Menotti M, Chisholm L, Lamarca A, Valle J, Sansom OJ, Springer C, Malliri A, Marais R, Pasca di Magliano M, Zelenay S, Morton JP, Jørgensen C. Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity. Cancer Cell. 2021; 39: 1227-1244
Latif AL, Newcombe A, Li S, Gilroy K, Robertson NA, Lei X, Stewart HJS, Cole J, Terradas MT, Rishi L, McGarry L, McKeeve C, Reid C, Clark W, Campos J, Kirschner K, Davis A, Lopez J, Sakamaki JI, Morton JP, et al. BRD4-mediated repression of p53 is a target for combination therapy in AML. Nat Commun. 2021;12:241.
Mackey JBG, McFarlane AJ, Jamieson T, Jackstadt R, Raffo-Iraolagoitia XL, Secklehner J, Cortes-Lavaud X, Fercoq F, Clarke W, Hedley A, Gilroy K, Lilla S, Vuononvirta J, Graham GJ, De Filippo K, Murphy DJ, Steele CW, Norman JC, Bird TG, Mann DA, Morton JP, Zanivan S, Sansom OJ, Carlin LM. Maturation, developmental site, and pathology dictate murine neutrophil function. bioRxiv. 2021.
Murphy KJ, Reed DA, Vennin C, Conway JRW, Nobis M, Yin JX, Chambers CR, Pereira BA, Lee V, Filipe EC, Trpceski M, Ritchie S, Lucas MC, Warren SC, Skhinas JN, Magenau A, Metcalf XL, Stoehr J, Major G, Parkin A, Bidanel R, Lyons RJ, Zaratzian A, Tayao M, Da Silva A, Abdulkhalek L, Gill AJ, Johns AL, Biankin AV, Samra J, Grimmond SM, Chou A, Goetz JG, Samuel MS, Lyons JG, Burgess A, Caldon CE, Horvath LG, Daly RJ, Gadegaard N, Wang Y, Sansom OJ, Morton JP, Cox TR, Pajic M, Herrmann D, Timpson P. Intravital imaging technology guides FAK-mediated priming in pancreatic cancer precision medicine according to Merlin status. Sci Adv. 2021;7:eabh0363.
Nacke M, Sandilands E, Nikolatou K, Román-Fernández Á, Mason S, Patel R, Lilla S, Yelland T, Galbraith LCA, Freckmann EC, McGarry L, Morton JP, Shanks E, Leung HY, Markert E, Ismail S, Zanivan S, Blyth K, Bryant DM. An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism. Nat Commun. 2021;12:1623.
Nielsen SR, Strøbech JE, Horton ER, Jackstadt R, Laitala A, Bravo MC, Maltese G, Jensen ARD, Reuten R, Rafaeva M, Karim SA, Hwang CI, Arnes L, Tuveson DA, Sansom OJ, Morton JP, Erler JT. Suppression of tumor-associated neutrophils by lorlatinib attenuates pancreatic cancer growth and improves treatment with immune checkpoint blockade. Nat Commun. 2021;12(1):3414.
Race AM, Sutton D, Hamm G, Maglennon G, Morton JP, Strittmatter N, Campbell A, Sansom OJ, Wang Y, Barry ST, Takáts Z, Goodwin RJA, Bunch J. Deep Learning-Based Annotation Transfer between Molecular Imaging Modalities: An Automated Workflow for Multimodal Data Integration. Anal Chem. 2021;93(6):3061-3071.
Sharbeen G, McCarroll JA, Akerman A, Kopecky C, Youkhana J, Kokkinos J, Holst J, Boyer C, Erkan M, Goldstein D, Timpson P, Cox TR, Pereira BA, Chitty JL, Fey SK, Najumudeen AK, Campbell AD, Sansom OJ, Ignacio RMC, Naim S, Liu J, Russia N, Lee J, Chou A, Johns A, Gill AJ, Gonzales-Aloy E, Gebski V, Guan YF, Pajic M, Turner N, Apte MV, Davis TP, Morton JP, Haghighi KS, Kasparian J, McLean BJ, Setargew YFI, Apgi A, Phillips PA. Cancer-associated fibroblasts in pancreatic ductal adenocarcinoma determine response to SLC7A11 inhibition. Cancer Res. 2021; 81:3461–79
Heinrich MA, Mostafa A, Morton JP, Hawinkels L, Prakash J. Translating complexity and heterogeneity of pancreatic tumor: 3D in vitro to in vivo models. Adv Drug Deliv Rev. 2021;174:265-293.
Watt DM, Morton JP. Heterogeneity in Pancreatic Cancer Fibroblasts-TGFβ as a Master Regulator? Cancers (Basel). 2021; 13:4984
Ahmed AA, Angell R, Oxenford S, Worthington J, Williams N, Barton N, Fowler TG, O'Flynn DE, Sunose M, McConville M, Vo T, Wilson WD, Karim SA, Morton JP, Neidle S. Asymmetrically Substituted Quadruplex-Binding Naphthalene Diimide Showing Potent Activity in Pancreatic Cancer Models. ACS Med Chem Lett. 2020;11(8):1634-1644.
Blagih J, Zani F, Chakravarty P, Hennequart M, Pilley S, Hobor S, Hock AK, Walton JB, Morton JP, Gronroos E, Mason S, Yang M, McNeish I, Swanton C, Blyth K, Vousden KH. Cancer-Specific Loss of p53 Leads to a Modulation of Myeloid and T Cell Responses. Cell reports. 2020;30:481-496.e486.
Brunton H, Caligiuri G, Cunningham R, Upstill-Goddard R, Bailey UM, Garner IM, Nourse C, Dreyer S, Jones M, Moran-Jones K, Wright DW, Paulus-Hock V, Nixon C, Thomson G, Jamieson NB, McGregor GA, Evers L, McKay CJ, Gulati A, Brough R, Bajrami I, Pettitt SJ, Dziubinski ML, Barry ST, Grutzmann R, Brown R, Curry E, Glasgow Precision Oncology L, Australian Pancreatic Cancer Genome I, Pajic M, Musgrove EA, Petersen GM, Shanks E, Ashworth A, Crawford HC, Simeone DM, Froeling FEM, Lord CJ, Mukhopadhyay D, Pilarsky C, Grimmond SE, Morton JP, Sansom OJ, Chang DK, Bailey PJ, Biankin AV. HNF4A and GATA6 Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer. Cell reports. 2020;31(6):107625.
Dreyer SB, Jamieson NB, Morton JP, Sansom OJ, Biankin AV, Chang DK. Pancreatic Cancer: From Genome Discovery to PRECISION-Panc. Clinical oncology (Royal College of Radiologists (Great Britain)). 2020; 32: 5-8
Michalopoulou E, Auciello FR, Bulusu V, Strachan D, Campbell AD, Tait-Mulder J, Karim SA, Morton JP, Sansom OJ, Kamphorst JJ. Macropinocytosis Renders a Subset of Pancreatic Tumor Cells Resistant to mTOR Inhibition. Cell reports. 2020; 30: 2729 - 2742.e4
Muthalagu N, Monteverde T, Raffo-Iraolagoitia X, Wiesheu R, Whyte D, Hedley A, Laing S, Kruspig B, Upstill-Goddard R, Shaw R, Neidler S, Rink C, Karim SA, Gyuraszova K, Nixon C, Clark W, Biankin AV, Carlin LM, Coffelt SB, Sansom OJ, Morton JP, Murphy DJ. Repression of the Type I Interferon pathway underlies MYC & KRAS-dependent evasion of NK & B cells in Pancreatic Ductal Adenocarcinoma. Cancer discovery. 2020;
Auciello FR, Bulusu V, Oon C, Tait-Mulder J, Berry M, Bhattacharyya S, Tumanov S, Allen-Petersen BL, Link J, Kendsersky ND, Vringer E, Schug M, Novo D, Hwang RF, Evans RM, Nixon C, Dorrell C, Morton JP, Norman JC, Sears RC, Kamphorst JJ, Sherman MH. A stromal lysolipid-autotaxin signaling axis promotes pancreatic tumor progression. Cancer Discov. 2019; doi: 10.1158/2159-8290.Cd-18-1212
Bott AJ, Shen J, Tonelli C, Zhan L, Sivaram N, Jiang YP, Yu X, Bhatt V, Chiles E, Zhong H, Maimouni S, Dai W, Velasquez S, Pan JA, Muthalagu N, Morton J, Anthony TG, Feng H, Lamers WH, Murphy DJ, Guo JY, Jin J, Crawford HC, Zhang L, White E, Lin RZ, Su X, Tuveson DA, Zong WX. Glutamine Anabolism Plays a Critical Role in Pancreatic Cancer by Coupling Carbon and Nitrogen Metabolism. Cell reports. 2019;29:1287-1298.e1286
Conway JR, Herrmann D, Evans TJ, Morton JP, Timpson P. Combating pancreatic cancer with PI3K pathway inhibitors in the era of personalised medicine. Gut. 2019; 68: 742-58.
Halbrook CJ, Pontious C, Kovalenko I, Lapienyte L, Dreyer S, Lee HJ, Thurston G, Zhang Y, Lazarus J, Sajjakulnukit P, Hong HS, Kremer DM, Nelson BS, Kemp S, Zhang L, Chang D, Biankin A, Shi J, Frankel TL, Crawford HC, Morton JP, Pasca di Magliano M, Lyssiotis CA. Macrophage-Released Pyrimidines Inhibit Gemcitabine Therapy in Pancreatic Cancer. Cell Metab. 2019; 29:P1390-1399.e6
Hari P, Millar FR, Tarrats N, Birch J, Quintanilla A, Rink CJ, Fernandez-Duran I, Muir M, Finch AJ, Brunton VG, Passos JF, Morton JP, Boulter L, Acosta JC. The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype. Science advances. 2019;5 doi:10.1126/sciadv.aaw0254
Leach J, Morton JP, Sansom OJ. Neutrophils: Homing in on the myeloid mechanisms of metastasis. Molecular immunology. 2019;110:69-76.
Liko D, Mitchell L, Campbell KJ, Ridgway RA, Jones C, Dudek K, King A, Bryson S, Stevenson D, Blyth K, Strathdee D, Morton JP, Bird TG, Knight JRP, Willis AE, Sansom OJ. Brf1 loss and not overexpression disrupts tissues homeostasis in the intestine, liver and pancreas. Cell Death Differ. 2019; 26: 2535–2550
Reader CS, Vallath S, Steele CW, Haider S, Brentnall A, Desai A, Moore KM, Jamieson NB, Chang D, Bailey P, Scarpa A, Lawlor R, Chelala C, Keyse SM, Biankin A, Morton JP, Evans TRJ, Barry ST, Sansom OJ, Kocher HM, Marshall JF. The integrin alphavbeta6 drives pancreatic cancer through diverse mechanisms and represents an effective target for therapy. The Journal of pathology. 2019; 249:332–342
Pereira BA, Vennin C, Papanicolaou M, Chambers CR, Herrmann D, Morton JP, Cox TR, Timpson P. CAF Subpopulations: A New Reservoir of Stromal Targets in Pancreatic Cancer. Trends in cancer. 2019;5:724-741.
Vennin C, Melenec P, Rouet R, Nobis M, Cazet AS, Murphy KJ, Herrmann D, Reed DA, Lucas MC, Warren SC, Elgundi Z, Pinese M, Kalna G, Roden D, Samuel M, Zaratzian A, Grey ST, Da Silva A, Leung W, Mathivanan S, Wang Y, Braithwaite AW, Christ D, Benda A, Parkin A, Phillips PA, Whitelock JM, Gill AJ, Sansom OJ, Croucher DR, Parker BL, Pajic M, Morton JP, Cox TR, Timpson P. CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan. Nature communications. 2019;10:3637.
Allen-Petersen BL, Risom T, Feng Z, Wang Z, Jenny ZP, Thoma MC, Pelz KR, Morton JP, Sansom OJ, Lopez CD, Sheppard B, Christensen DJ, Ohlmeyer M, Narla G, Sears RC. Activation of PP2A and inhibition of mTOR synergistically reduce MYC signaling and decrease tumor growth in pancreatic ductal adenocarcinoma. Cancer Res 2018; 79
Besray Unal E, Kiel C, Benisty H, Campbell A, Pickering K, Bluthgen N, Sansom OJ, Serrano L. Systems level expression correlation of Ras GTPase regulators. Cell Commun Signal 2018; 16(1): 46.
Candido JB, Morton JP, Bailey P, Campbell AD, Karim SA, Jamieson T, Lapienyte L, Gopinathan A, Clark W, McGhee EJ, Wang J, Escorcio-Correia M, Zollinger R, Roshani R, Drew L, et al. CSF1R(+) Macrophages Sustain Pancreatic Tumor Growth through T Cell Suppression and Maintenance of Key Gene Programs that Define the Squamous Subtype. Cell Rep 2018;23(5):1448-60.
Chou A, Froio D, Nagrial AM, Parkin A, Murphy KJ, Chin VT, Wohl D, Steinmann A, Stark R, Drury A, Walters SN, Vennin C, Burgess A, Pinese M, Chantrill LA, et al. Tailored first-line and second-line CDK4-targeting treatment combinations in mouse models of pancreatic cancer. Gut 2018; 67: 2142-55.
Conway JRW, Warren SC, Herrmann D, Murphy KJ, Cazet AS, Vennin C, Shearer RF, Killen MJ, Magenau A, Melenec P, Pinese M, Nobis M, Zaratzian A, Boulghourjian A, Da Silva AM, et al. Intravital Imaging to Monitor Therapeutic Response in Moving Hypoxic Regions Resistant to PI3K Pathway Targeting in Pancreatic Cancer. Cell Rep 2018;23(11):3312-3326
Farrell AS, Joly MM, Allen-Petersen BL, Worth PJ, Lanciault C, Sauer D, Link J, Pelz C, Heiser LM, Morton JP, Muthalagu N, Hoffman MT, Manning SL, Pratt ED, Kendsersky ND, et al. MYC regulates ductal-neuroendocrine lineage plasticity in pancreatic ductal adenocarcinoma associated with poor outcome and chemoresistance. Nat Commun 2017; 8(1): 1728.
Godfrey JD, Morton JP, Wilczynska A, Sansom OJ, Bushell MD. MiR-142-3p is downregulated in aggressive p53 mutant mouse models of pancreatic ductal adenocarcinoma by hypermethylation of its locus. Cell Death Dis 2018;9(6):644.
Mackay HL, Moore D, Hall C, Birkbak NJ, Jamal-Hanjani M, Karim SA, Phatak VM, Pinon L, Morton JP, Swanton C, Le Quesne J, Muller PAJ. Genomic instability in mutant p53 cancer cells upon entotic engulfment. Nat Commun 2018;9(1):3070.
Marchetti C, Zyner KG, Ohnmacht SA, Robson M, Haider SM, Morton JP, Marsico G, Vo T, Laughlin-Toth S, Ahmed AA, Di Vita G, Pazitna I, Gunaratnam M, Besser RJ, Andrade ACG, et al. Targeting Multiple Effector Pathways in Pancreatic Ductal Adenocarcinoma with a G-Quadruplex-Binding Small Molecule. J Med Chem 2018;61(6):2500-17.
Meiser J, Schuster A, Pietzke M, Vande Voorde J, Athineos D, Oizel K, Burgos-Barragan G, Wit N, Dhayade S, Morton JP, Dornier E, Sumpton D, Mackay GM, Blyth K, Patel KJ, et al. Increased formate overflow is a hallmark of oxidative cancer. Nat Commun 2018;9(1):1368.
Novo D, Heath N, Mitchell L, Caligiuri G, MacFarlane A, Reijmer D, Charlton L, Knight J, Calka M, McGhee E, Dornier E, Sumpton D, Mason S, Echard A, Klinkert K, et al. Mutant p53s generate pro-invasive niches by influencing exosome podocalyxin levels. Nat Commun 2018; 9: 5069.
Schofield HK, Zeller J, Espinoza C, Halbrook CJ, Del Vecchio A, Magnuson B, Fabo T, Daylan AEC, Kovalenko I, Lee HJ, Yan W, Feng Y, Karim SA, Kremer DM, Kumar-Sinha C, et al. Mutant p53R270H drives altered metabolism and increased invasion in pancreatic ductal adenocarcinoma. JCI Insight 2018;3(2).
Vennin C, Murphy M, Morton JP, Cox TR, Pajic M, Timpson P. Reshaping the Tumor Stroma as a New Approach for Treatment of Pancreatic Cancer. Gastroenterology 2018;154: 820-838
Warren SC, Nobis M, Magenau A, Mohammed YH, Herrmann D, Moran I, Vennin C, Conway JR, Melenec P, Cox TR, Wang Y, Morton JP, Welch HC, Strathdee D, Anderson KI, et al. Removing physiological motion from intravital and clinical functional imaging data. Elife 2018;7.
Conway JR, Herrmann D, Evans TJ, Morton JP, Timpson P. Combating pancreatic cancer with PI3K pathway inhibitors in the era of personalised medicine. Gut 2018.
Chuvin N, Vincent DF, Pommier RM, Alcaraz LB, Gout J, Caligaris C, Yacoub K, Cardot V, Roger E, Kaniewski B, Martel S, Cintas C, Goddard-Leon S, Colombe A, Valantin J, Gadot N, Servoz E, Morton J, Goddard I, Couvelard A et al. Acinar-to-Ductal Metaplasia Induced by Transforming Growth Factor Beta Facilitates KRAS(G12D)-driven Pancreatic Tumorigenesis. Cell Mol Gastroenterol Hepatol 2017; 4: 263-82
Conway JRW, Vennin C, Cazet AS, Herrmann D, Murphy KJ, Warren SC, Wullkopf L, Boulghourjian A, Zaratzian A, Da Silva AM, Pajic M, Morton JP, Cox TR, Timpson P (2017) Three-dimensional organotypic matrices from alternative collagen sources as pre-clinical models for cell biology. Sci Rep 7: 16887
Farrell AS, Joly MM, Allen-Petersen BL, Worth PJ, Lanciault C, Sauer D, Link J, Pelz C, Heiser LM, Morton JP, Muthalagu N, Hoffman MT, Manning SL, Pratt ED, Kendsersky ND, Egbukichi N, Amery TS, Thoma MC, Jenny ZP, Rhim AD et al. MYC regulates ductal-neuroendocrine lineage plasticity in pancreatic ductal adenocarcinoma associated with poor outcome and chemoresistance. Nat Commun 2017; 8: 1728
Gundry C, Marco S, Rainero E, Miller B, Dornier E, Mitchell L, Caswell PT, Campbell AD, Hogeweg A, Sansom OJ, Morton JP, Norman JC. Phosphorylation of Rab-coupling protein by LMTK3 controls Rab14-dependent EphA2 trafficking to promote cell:cell repulsion. Nat Commun 2017; 8: 14646
Harris NL, Vennin C, Conway JR, Vine KL, Pinese M, Cowley MJ, Shearer RF, Lucas MC, Herrmann D, Allam AH, Pajic M, Morton JP, Australian Pancreatic Cancer Genome I, Biankin AV, Ranson M, Timpson P, Saunders DN. SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer. Oncogene 2017; 36: 4288-98
Humphris JL, Patch AM, Nones K, Bailey PJ, Johns AL, McKay S, Chang DK, Miller DK, Pajic M, Kassahn KS, Quinn MC, Bruxner TJ, Christ AN, Harliwong I, Idrisoglu S, Manning S, Nourse C, Nourbakhsh E, Stone A, Wilson PJ et al. Hypermutation In Pancreatic Cancer. Gastroenterology 2017; 152: 68-74.e2
Nobis M, Herrmann D, Warren SC, Kadir S, Leung W, Killen M, Magenau A, Stevenson D, Lucas MC, Reischmann N, Vennin C, Conway JRW, Boulghourjian A, Zaratzian A, Law AM, Gallego-Ortega D, Ormandy CJ, Walters SN, Grey ST, Bailey J et al. A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts. Cell Rep 2017; 21: 274-88
Rath N, Morton JP, Julian L, Helbig L, Kadir S, McGhee EJ, Anderson KI, Kalna G, Mullin M, Pinho AV, Rooman I, Samuel MS, Olson MF. ROCK signaling promotes collagen remodeling to facilitate invasive pancreatic ductal adenocarcinoma tumor cell growth. EMBO Mol Med 2017; 9: 198-218
Rice AJ, Cortes E, Lachowski D, Cheung BCH, Karim SA, Morton JP, Del Rio Hernandez A. Matrix stiffness induces epithelial-mesenchymal transition and promotes chemoresistance in pancreatic cancer cells. Oncogenesis 2017; 6: e352
Ritschka B, Storer M, Mas A, Heinzmann F, Ortells MC, Morton JP, Sansom OJ, Zender L, Keyes WM. The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration. Genes Dev 2017; 31: 172-83
Rosenfeldt MT, O'Prey J, Flossbach L, Nixon C, Morton JP, Sansom OJ, Ryan KM. PTEN deficiency permits the formation of pancreatic cancer in the absence of autophagy. Cell Death Differ 2017; 24: 1303-4
Vennin C, Chin VT, Warren SC, Lucas MC, Herrmann D, Magenau A, Melenec P, Walters SN, Del Monte-Nieto G, Conway JR, Nobis M, Allam AH, McCloy RA, Currey N, Pinese M, Boulghourjian A, Zaratzian A, Adam AA, Heu C, Nagrial AM et al. Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis. Sci Transl Med 2017; 9: pii: eaai8504
Morton JP, Sansom OJ. CXCR2 inhibition in pancreatic cancer: opportunities for immunotherapy? Immunotherapy 2017; 9: 9-12
Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJ, Quinn MC, Nourse C, Murtaugh LC, Harliwong I, Idrisoglu S, Manning S, Nourbakhsh E, Wani S, Fink L, Holmes O, Chin V, Anderson MJ, Kazakoff S, Leonard C, Newell F, Waddell N, Wood S, Xu Q, Wilson PJ, Cloonan N, Kassahn KS, Taylor D, Quek K, Robertson A, Pantano L, Mincarelli L, Sanchez LN, Evers L, Wu J, Pinese M, Cowley MJ, Jones MD, Colvin EK, Nagrial AM, Humphrey ES, Chantrill LA, Mawson A, Humphris J, Chou A, Pajic M, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Lovell JA, Merrett ND, Toon CW, Epari K, Nguyen NQ, Barbour A, Zeps N, Moran-Jones K, Jamieson NB, Graham JS, Duthie F, Oien K, Hair J, Grutzmann R, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Rusev B, Capelli P, Salvia R, Tortora G, Mukhopadhyay D, Petersen GM, Australian Pancreatic Cancer Genome Initiative, Munzy DM, Fisher WE, Karim SA, Eshleman JR, Hruban RH, Pilarsky C, Morton JP, Sansom OJ, Scarpa A, Musgrove EA, Bailey UM, Hofmann O, Sutherland RL, Wheeler DA, Gill AJ, Gibbs RA, Pearson JV, Waddell N, Biankin AV & Grimmond SM (2016) Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 531, 47-52.
Driscoll DR, Karim SA, Sano M, Gay DM, Jacob W, Yu J, Mizukami Y, Gopinathan A, Jodrell DI, Evans TR, Bardeesy N, Hall MN, Quattrochi BJ, Klimstra DS, Barry ST, Sansom OJ, Lewis BC & Morton JP (2016) mTORC2 Signaling Drives the Development and Progression of Pancreatic Cancer. Cancer Res. 76, 6911-23.
Erami Z, Herrmann D, Warren SC, Nobis M, McGhee EJ, Lucas MC, Leung W, Reischmann N, Mrowinska A, Schwarz JP, Kadir S, Conway JR, Vennin C, Karim SA, Campbell AD, Gallego-Ortega D, Magenau A, Murphy KJ, Ridgway RA, Law AM, Walters SN, Grey ST, Croucher DR, Zhang L, Herzog H, Hardeman EC, Gunning PW, Ormandy CJ, Evans TR, Strathdee D, Sansom OJ, Morton JP, Anderson KI & Timpson P (2016) Intravital FRAP Imaging using an E-cadherin-GFP Mouse Reveals Disease- and Drug-Dependent Dynamic Regulation of Cell-Cell Junctions in Live Tissue. Cell Rep. 14, 152-67.
Guest RV, Boulter L, Dwyer BJ, Kendall TJ, Man TY, Minnis-Lyons SE, Lu WY, Robson AJ, Gonzalez SF, Raven A, Wojtacha D, Morton JP, Komuta M, Roskams T, Wigmore SJ, Sansom OJ & Forbes SJ (2016) Notch3 drives development and progression of cholangiocarcinoma. Proc Natl Acad Sci U S A. 113, 12250-5.
Matzke-Ogi A, Jannasch K, Shatirishvili M, Fuchs B, Chiblak S, Morton J, Tawk B, Lindner T, Sansom O, Alves F, Warth A, Schwager C, Mier W, Kleeff J, Ponta H, Abdollahi A & Orian-Rousseau V (2016) Inhibition of Tumor Growth and Metastasis in Pancreatic Cancer Models by Interference With CD44v6 Signaling. Gastroenterology. 150, 513-25.
Lesina M, Wormann SM, Morton J, Diakopoulos KN, Korneeva O, Wimmer M, Einwachter H, Sperveslage J, Demir IE, Kehl T, Saur D, Sipos B, Heikenwalder M, Steiner JM, Wang TC, Sansom OJ, Schmid RM & Algul H (2016) RelA regulates CXCL1/CXCR2-dependent oncogene-induced senescence in murine Kras-driven pancreatic carcinogenesis. J Clin Invest. 126, 2919-32.
Steele CW, Karim SA, Leach JD, Bailey P, Upstill-Goddard R, Rishi L, Foth M, Bryson S, McDaid K, Wilson Z, Eberlein C, Candido JB, Clarke M, Nixon C, Connelly J, Jamieson N, Carter CR, Balkwill F, Chang DK, Evans TR, Strathdee D, Biankin AV, Nibbs RJ, Barry ST, Sansom OJ & Morton JP (2016) CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma. Cancer Cell. 29, 832-45.
In vivo models are an important tool to recapitulate human cancer and interrogate aspects of the disease within a biological context. Validating in vitro discoveries in physiologically relevant models in this way will expedite novel therapeutic approaches for patient benefit. The group has expertise in modelling different cancer types but has a specific interest in breast cancer, and how metabolic pathways and certain signalling nodes such as the RUNX/CBFβ transcriptional complex and pro-survival factor MCL-1, contribute to tumour progression and metastasis.
The RUNX genes are essential regulators in mammalian development, most notably for bone and blood cell lineages. Like many genes important for normal development, the RUNX genes are linked to human cancer, but interestingly have been found to both promote and suppress tumour formation, a paradox we are exploring. We have shown that high expression of RUNX1 and RUNX2 in breast cancer correlates with specific subtypes of the disease and with poorer patient prognosis. We are now investigating the functionality of these genes in epithelial cancers and have shown that RUNX2 has a role in mammary stem/progenitor cells.
Other funding:
Campbell KJ, Mason SM, Winder ML, Willemsen RBE, Cloix C, Lawson H, Rooney N, Dhayade S, Sims AH, Blyth K, Tait SWG. Breast cancer dependence on MCL-1 is due to its canonical anti-apoptotic function. Cell Death Differ. 2021. 28; 2589–600
Rooney N, Mason SM, McDonald L, Däbritz JHM, Campbell KJ, Hedley A, Howard S, Athineos D, Nixon C, Clark W, Leach JDG, Sansom OJ, Edwards J, Cameron ER, Blyth K RUNX1 is a driver of renal cell carcinoma correlating with clinical outcome Cancer Res. 2020;
Blyth K, Carter P, Morrissey B, Chelala C, Jones L, Holen I and Speirs V. SEARCHBreast: a new resource to locate and share surplus archival material from breast cancer animal models to help address the 3Rs. Breast Cancer Res Treat. 2016; 56:447-52
Ferrari N, Riggio AI, Mason S, McDonald L, King A, Higgins T, Rosewell I, Neil JC, Smalley MJ, Sansom OJ, Morris J, Cameron ER, Blyth K. Runx2 contributes to the regenerative potential of the mammary epithelium. Scientific Reports. 2015; 5:15658
Ferrari N, Mohammed ZMA, Nixon C, Mason SM, Mallon E, McMillan DC, Morris JS, Cameron ER, Blyth K. Expression of RUNX1 correlates with poor patient prognosis in triple negative breast cancer. PLOS One. 2014 9:e100759
McDonald L, Ferrari N, Terry A, Bell M, Mohammed ZM, Orange C, Jenkins A, Muller WJ, Gusterson BA, Neil JC, Edwards J, Morris JS, Cameron ER, Blyth K. RUNX2 correlates with subtype-specific breast cancer in a human tissue microarray and ectopic expression of Runx2 perturbs differentiation in the mouse mammary gland. Dis Model Mech. 2014 7:525-34
Blyth K, Vaillant F, Hanlon L, Mackay N, Bell M, Jenkins A, Neil JC, Cameron ER. Runx2 and MYC collaborate in lymphoma development by suppressing apoptotic and growth arrest pathways in vivo. Cancer Res. 2006; 66:2195-201
Blyth K, Cameron ER, Neil JC. The RUNX genes: gain or loss of function in cancer. Nat Rev Cancer. 2005; 5:376-87
1997: PhD, University of Glasgow, Supervisors Ewan Cameron & Moyra Campbell
1991: BSc, Biochemistry (Honours), University of Glasgow
2019-present: Professor, School of Cancer Sciences, University of Glasgow
2009-present: Head of Transgenic Models, Cancer Research UK Scotland Institute, Glasgow
1997-2008: Postdoctoral Fellow, Molecular Oncology Lab, University of Glasgow
1991-1996: Research Assistant, University of Glasgow
Ackermann T, Shokry E, Deshmukh R, Anand J, Galbraith LCA, Mitchell L, Rodriguez-Blanco G, Villar VH, Sterken BA, Nixon C, Zanivan S, Blyth K, Sumpton D, Tardito S. Breast cancer secretes anti-ferroptotic MUFAs and depends on selenoprotein synthesis for metastasis. bioRxiv. 2024:2023.2006.2013.544588.
Fercoq F, Cairns GS, Donatis MD, Mackey JBG, Floerchinger A, McFarlane A, Raffo-Iraolagoitia XL, Whyte D, Arnott LWG, Nixon C, Wiesheu R, Kilbey A, Brown L, Al-Khalidi S, Norman JC, Roberts EW, Blyth K, Coffelt SB, Carlin LM. Integrin inactivation slows down neutrophils congesting the pre-metastatic lung in a model of breast cancer. bioRxiv. 2024:2024.2003.2019.585724.
Gounis M, Campos AV, Shokry E, Mitchell L, Dornier E, Rooney N, Dhayade S, Pardo L, Moore M, Novo D, Mowat J, Jamieson C, Kay E, Zanivan S, Nixon C, Macpherson I, Tardito S, Sumpton D, Blyth K, Norman JC, Clarke CJ. Metabolic adaptations of micrometastases alter EV production to generate invasive microenvironments. bioRxiv. 2024:2024.2005.2012.593552.
Mahmood M, Liu EM, Shergold AL, Tolla E, Tait-Mulder J, Huerta-Uribe A, Shokry E, Young AL, Lilla S, Kim M, Park T, Boscenco S, Manchon JL, Rodríguez-Antona C, Walters RC, Springett RJ, Blaza JN, Mitchell L, Blyth K, Zanivan S, Sumpton D, Roberts EW, Reznik E, Gammage PA. Mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade response in melanoma. Nat Cancer. 2024.
Mardilovich K, Naylor G, Julian L, Phinichkusolchit N, Keeshan K, Blyth K, Olson MF. Caspase-resistant ROCK1 expression prolongs survival of Eµ-Myc B cell lymphoma mice. Dis Model Mech. 2024.
Santi A, Kay EJ, Neilson LJ, McGarry L, Lilla S, Mullin M, Paul NR, Fercoq F, Koulouras G, Rodriguez Blanco G, Athineos D, Mason S, Hughes M, Thomson G, Kieffer Y, Nixon C, Blyth K, Mechta-Grigoriou F, Carlin LM, Zanivan S. Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Sci Signal. 2024;17(827):eade0580.
Whyte D, Voorde JV, Sumpton D, Dhayade S, Dornier E, Moore M, Novo D, Peters J, Wiesheu R, Mackey JBG, McFarlane AJ, Fercoq F, Fisher S, Caballero CD, Gilroy K, Redmond KL, Mitchell LE, Anderson E, Thomson G, Dzierozynski LN, Saab JJA, Lewis CA, Muir A, Halbrook CJ, Strathdee D, Jackstadt R, Nixon C, Dunne P, Steele CW, Carlin LM, Macpherson IR, Roberts EW, Coffelt SB, Blyth K, Sansom OJ, Norman JC, Clarke CJ. Uridine Phosphorylase-1 supports metastasis of mammary cancer by altering immune and extracellular matrix landscapes of the lung. bioRxiv. 2024:2024.2007.2002.601676.
Ackermann T, Shokry E, Deshmukh R, Anand J, Galbraith LCA, Mitchell L, Rodriguez-Blanco G, Villar VH, Sterken BA, Nixon C, Zanivan S, Blyth K, Sumpton D, Tardito S. Paracrine secretion of MUFAs prevents ferroptosis in triple-negative breast cancer and reveals selenocysteine synthesis dependency for lung metastasis. bioRxiv. 2023;Volume:2023.2006.2013.544588.
Bailey P, Ridgway RA, Cammareri P, Treanor-Taylor M, Bailey UM, Schoenherr C, Bone M, Schreyer D, Purdie K, Thomson J, Rickaby W, Jackstadt R, Campbell AD, Dimonitsas E, Stratigos AJ, Arron ST, Wang J, Blyth K, Proby CM, Harwood CA, Sansom OJ, Leigh IM, Inman GJ. Driver gene combinations dictate cutaneous squamous cell carcinoma disease continuum progression. Nat Commun. 2023;14:5211.
Dzien P, Mackintosh A, Malviya G, Johnson E, Soloviev D, Brown G, Uribe AH, Nixon C, Lyons SK, Maddocks O, Blyth K, Lewis DY. Positron emission tomography imaging of the sodium iodide symporter senses real-time energy stress in vivo. Cancer Metab. 2023;11(1):14.
Edwards SC, Hedley A, Hoevenaar WHM, Wiesheu R, Glauner T, Kilbey A, Shaw R, Boufea K, Batada N, Hatano S, Yoshikai Y, Blyth K, Miller C, Kirschner K, Coffelt SB. PD-1 and TIM-3 differentially regulate subsets of mouse IL-17A-producing γδ T cells. J Exp Med. 2023;220: e20211431
Martin TP, MacDonald EA, Bradley A, Watson H, Saxena P, Rog-Zielinska EA, Raheem A, Fisher S, Elbassioni AAM, Almuzaini O, Booth C, Campbell M, Riddell A, Herzyk P, Blyth K, Nixon C, Zentilin L, Berry C, Braun T, Giacca M, McBride MW, Nicklin SA, Cameron ER, Loughrey CM. RNA interference or small molecule inhibition of Runx1 in the border zone prevents cardiac contractile dysfunction following myocardial infarction. Cardiovasc Res. 2023;10.1093/cvr/cvad107.
Papalazarou V, Newman AC, Huerta-Uribe A, Legrave NM, Falcone M, Zhang T, McGarry L, Athineos D, Shanks E, Blyth K, Vousden KH, Maddocks ODK. Phenotypic profiling of solute carriers characterizes serine transport in cancer. Nat Metab. 2023.
Román-Fernández A, Mansour MA, Kugeratski FG, Anand J, Sandilands E, Galbraith L, Rakovic K, Freckmann EC, Cumming EM, Park J, Nikolatou K, Lilla S, Shaw R, Strachan D, Mason S, Patel R, McGarry L, Katoch A, Campbell KJ, Nixon C, Miller CJ, Leung HY, Le Quesne J, Norman JC, Zanivan S, Blyth K, Bryant DM. Spatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function. Sci Adv. 2023;9:eabq1858.
Sandilands E, Freckmann EC, Cumming EM, Román-Fernández A, McGarry L, Anand J, Galbraith L, Mason S, Patel R, Nixon C, Cartwright J, Leung HY, Blyth K, Bryant DM. The small GTPase ARF3 controls invasion modality and metastasis by regulating N-cadherin levels. Journal of Cell Biology. 2023;222:e202206115
Santi A, Kay EJ, Neilson LJ, McGarry L, Lilla S, Mullin M, Paul NR, Fercoq F, Koulouras G, Blanco GR, Athineos D, Mason S, Hughes M, Kieffer Y, Nixon C, Blyth K, Mechta-Grigoriou F, Carlin LM, Zanivan S. Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. bioRxiv. 2023;Volume:2023.2001.2013.523951.
Suzuki T, Kilbey A, Casa Rodriguez N, Lawlor A, Georgakopoulou A, Hayman H, Yin Swe KL, Nordin A, Cantù C, Vantourout P, Ridgway RA, Byrne RM, Chen L, Verzi MP, Gay DM, Gil Vazquez E, Belnoue-Davis HL, Gilroy K, Kostner AH, Kersten C, Thuwajit C, Andersen DK, Wiesheu R, Jandke A, Blyth K, Roseweir AK, Leedham SJ, Dunne PD, Edwards J, Hayday A, Sansom OJ, Coffelt SB. β-catenin drives butyrophilin-like molecule loss and γδ T-cell exclusion in colon cancer. Cancer Immunology Research. 2023;11: 1137–1155.
Villar VH, Allega MF, Deshmukh R, Ackermann T, Nakasone MA, Vande Voorde J, Drake TM, Oetjen J, Bloom A, Nixon C, Müller M, May S, Tan EH, Vereecke L, Jans M, Blancke G, Murphy DJ, Huang DT, Lewis DY, Bird TG, Sansom OJ, Blyth K, Sumpton D, Tardito S. Hepatic glutamine synthetase controls N5-methylglutamine in homeostasis and cancer. Nature Chemical Biology. 2023;19:292-300.
Wiesheu R, Edwards SC, Hedley A, Tosolini M, Silva MGFFd, Sumaria N, Optaczy Y, Hill DG, Hayes AJ, Hay J, Kilbey A, Michie AM, Graham GJ, Manoharan A, Halsey C, Jones GW, Blyth K, Fournie J-J, Pennington DJ, Bekiaris V, Coffelt SB. IL-27 maintains cytotoxic Ly6C+ γδ T cells that arise from immature precursors. bioRxiv. 2023:2023.2010.2026.564114.
Khan AS, Campbell KJ, Cameron ER, Blyth K. The RUNX/CBFβ Complex in Breast Cancer: A Conundrum of Context. Cells. 2023;12:641
Blomme A, Peter C, Mui E, Rodriguez Blanco G, An N, Mason LM, Jamieson LE, McGregor GH, Lilla S, Ntala C, Patel R, Thiry M, Kung SHY, Leclercq M, Ford CA, Rushworth LK, McGarry DJ, Mason S, Repiscak P, Nixon C, Salji MJ, Markert E, MacKay GM, Kamphorst JJ, Graham D, Faulds K, Fazli L, Gleave ME, Avezov E, Edwards J, Yin H, Sumpton D, Blyth K, Close P, Murphy DJ, Zanivan S, Leung HY. THEM6-mediated reprogramming of lipid metabolism supports treatment resistance in prostate cancer. EMBO Molecular Medicine. 2022;14:e14764
Falcone M, Uribe AH, Papalazarou V, Newman AC, Athineos D, Stevenson K, Sauvé CG, Gao Y, Kim JK, Del Latto M, Kierstead M, Wu C, Smith JJ, Romesser PB, Chalmers AJ, Blyth K, Maddocks ODK. Sensitisation of cancer cells to radiotherapy by serine and glycine starvation. Br J Cancer. 2022;127:1773-1786.
Humpton TJ, Hall H, Kiourtis C, Nixon C, Clark W, Hedley A, Shaw R, Bird TG, Blyth K, Vousden KH. p53-mediated redox control promotes liver regeneration and maintains liver function in response to CCl(4). Cell Death Differ. 2022;29:514-526.
Humpton TJ, Hock AK, Kiourtis C, De Donatis M, Fercoq F, Nixon C, Bryson S, Strathdee D, Carlin LM, Bird TG, Blyth K, Vousden KH. A noninvasive iRFP713 p53 reporter reveals dynamic p53 activity in response to irradiation and liver regeneration in vivo. Sci Signal. 2022;15:eabd9099.
Jaber-Hijazi F, Swaminathan K, Gilroy K, Wenzel AT, Lagnado A, Kirschner K, Robertson N, Reid C, Fullarton N, Pawlikowski J, Blyth K, Mesirov JP, Rai TS, Passos JF, Machesky LM, Adams PD. Inactivation of histone chaperone HIRA unmasks a link between normal embryonic development of melanoblasts and maintenance of adult melanocyte stem cells. bioRxiv; 10.1101/2022.04.22.4891662022:2022.2004.2022.489166.
Kay EJ, Paterson K, Riero-Domingo C, Sumpton D, Däbritz JHM, Tardito S, Boldrini C, Hernandez-Fernaud JR, Athineos D, Dhayade S, Stepanova E, Gjerga E, Neilson LJ, Lilla S, Hedley A, Koulouras G, McGregor G, Jamieson C, Johson RM, Park M, Kirschner K, Miller C, Kamphorst JJ, Loayza-Puch F, Saez-Rodriguez J, Mazzone M, Blyth K, Zagoni M, Zanivan S. Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix. Nature Metabolism. 2022;4(6):693-710.
Koessinger AL, Cloix C, Koessinger D, Heiland DH, Bock FJ, Strathdee K, Kinch K, Martínez-Escardó L, Paul NR, Nixon C, Malviya G, Jackson MR, Campbell KJ, Stevenson K, Davis S, Elmasry Y, Ahmed A, O’Prey J, Ichim G, Schnell O, Stewart W, Blyth K, Ryan KM, Chalmers AJ, Norman JC, Tait SWG. Increased apoptotic sensitivity of glioblastoma enables therapeutic targeting by BH3-mimetics. Cell Death & Differentiation. 2022;29:2089–2104
Spiliopoulou P, Spear S, Mirza H, Garner I, McGarry L, Grundland Freile F, Cheng Z, Ennis DP, Iyer NR, McNamara S, Natoli M, Mason SM, Blyth K, Adams PD, Roxburgh P, Fuchter MJ, Brown R, McNeish IA. Dual G9A/EZH2 inhibition stimulates anti-tumour immune response in ovarian high grade serous carcinoma. Mol Cancer Ther. 2022;21:522–534
Suzuki T, Kilbey A, Ridgway RA, Hayman H, Byrne R, Casa Rodriguez N, Georgakopoulou A, Chen L, Verzi M, Gay DM, Vzquez EG, Belnoue-Davis HL, Gilroy K, Kostner AH, Kersten C, Thuwajit C, Andersen D, Wiesheu R, Jandke A, Roberts N, Blyth K, Roseweir A, Leedham SJ, Dunne PD, Edwards J, Hayday A, Sansom OJ, Coffelt SB. β-catenin obstructs γδ T cell immunosurveillance in colon cancer through loss of BTNL expression. bioRxiv. 2022;Volume:2022.2006.2010.495115.
Bock FJ, Sedov E, Koren E, Koessinger AL, Cloix C, Zerbst D, Athineos D, Anand J, Campbell KJ, Blyth K, Fuchs Y, Tait SWG. Apoptotic stress-induced FGF signalling promotes non-cell autonomous resistance to cell death. Nat Commun. 2021 Nov 12;12(1):6572.
Borrello M, Rita Emma M, Listi A, Rubis M, Coslet S, Augello G, Cusimano A, Cabibi D, Porcasi R, Giannitrapani L, Soresi M, Pantuso G, Blyth K, Montalto G, Pin C, Cervello M, Iovanna J. NUPR1 protects liver from lipotoxic injury by improving the endoplasmic reticulum stress response. Faseb j. 2021;35(3):e21395.
Campbell KJ, Mason SM, Winder ML, Willemsen RBE, Cloix C, Lawson H, Rooney N, Dhayade S, Sims AH, Blyth K, Tait SWG. Breast cancer dependence on MCL-1 is due to its canonical anti-apoptotic function. Cell Death Differ. 2021. 28; 2589–600
Dayal JHS, Mason SM, Salas-Alanis JC, McGrath JA, Taylor RG, Mellerio JE, Blyth K, South AP, Inman GJ. Heterogeneous addiction to transforming growth factor-beta signalling in recessive dystrophic epidermolysis bullosa-associated cutaneous squamous cell carcinoma. Br J Dermatol. 2021;184:697-708.
Edwards SC, Hedley A, Hoevenaar WHM, Glauner T, Wiesheu R, Kilbey A, Shaw R, Boufea K, Batada N, Blyth K, Miller C, Kirschner K, Coffelt SB. Single-cell analysis uncovers differential regulation of lung γδ T cell subsets by the co-inhibitory molecules, PD-1 and TIM-3. bioRxiv. 2021.
Floerchinger A, Murphy KJ, Latham SL, Warren SC, McCulloch AT, Lee YK, Stoehr J, Mélénec P, Guaman CS, Metcalf XL, Lee V, Zaratzian A, Da Silva A, Tayao M, Rolo S, Phimmachanh M, Sultani G, McDonald L, Mason SM, Ferrari N, Ooms LM, Johnsson AE, Spence HJ, Olson MF, Machesky LM, Sansom OJ, Morton JP, Mitchell CA, Samuel MS, Croucher DR, Welch HCE, Blyth K, Caldon CE, Herrmann D, Anderson KI, Timpson P, Nobis M. Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: Guidance using optical window intravital FRET imaging. Cell Rep. 2021;36(11):109689.
Humpton TJ, Nomura K, Weber J, Magnussen HM, Hock AK, Nixon C, Dhayade S, Stevenson D, Huang DT, Strathdee D, Blyth K, Vousden KH. Differential requirements for MDM2 E3 activity during embryogenesis and in adult mice. Genes & development. 2021;35(1-2):117-132.
Johnson SA, Ormsby MJ, Wessel HM, Hulme HE, Bravo-Blas A, McIntosh A, Mason S, Coffelt SB, Tait SWG, Mowat AM, Milling SWF, Blyth K, Wall DM. Monocytes mediate Salmonella Typhimurium-induced tumour growth inhibition in a mouse melanoma model. Eur J Immunol. 2021:51:3228-3238
Latif AL, Newcombe A, Li S, Gilroy K, Robertson NA, Lei X, Stewart HJS, Cole J, Terradas MT, Rishi L, McGarry L, McKeeve C, Reid C, Clark W, Campos J, Kirschner K, Davis A, Lopez J, Sakamaki JI, Morton JP, et al. BRD4-mediated repression of p53 is a target for combination therapy in AML. Nat Commun. 2021;12:241.
McGarry DJ, Armstrong G, Castino G, Mason S, Clark W, Shaw R, McGarry L, Blyth K, Olson MF. MICAL1 regulates actin cytoskeleton organization, directional cell migration and the growth of human breast cancer cells as orthotopic xenograft tumours. Cancer Lett. 2021;519:226-236.
Nacke M, Sandilands E, Nikolatou K, Román-Fernández Á, Mason S, Patel R, Lilla S, Yelland T, Galbraith LCA, Freckmann EC, McGarry L, Morton JP, Shanks E, Leung HY, Markert E, Ismail S, Zanivan S, Blyth K, Bryant DM. An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism. Nat Commun. 2021;12:1623.
Newman AC, Falcone M, Huerta Uribe A, Zhang T, Athineos D, Pietzke M, Vazquez A, Blyth K, Maddocks ODK. Immune-regulated IDO1-dependent tryptophan metabolism is source of one-carbon units for pancreatic cancer and stellate cells. Mol Cell. 2021; 81:2290-2302
Rudzka DA, Mason S, Neilson M, McGarry L, Kalna G, Hedley A, Blyth K, Olson MF. Selection of established tumour cells through narrow diameter micropores enriches for elevated Ras/Raf/MEK/ERK MAPK signalling and enhanced tumour growth. Small GTPases. 2021;12(4):294-310.
Tajan M, Hennequart M, Cheung EC, Zani F, Hock AK, Legrave N, Maddocks ODK, Ridgway RA, Athineos D, Suárez-Bonnet A, Ludwig RL, Novellasdemunt L, Angelis N, Li VSW, Vlachogiannis G, Valeri N, Mainolfi N, Suri V, Friedman A, Manfredi M, et al. Serine synthesis pathway inhibition cooperates with dietary serine and glycine limitation for cancer therapy. Nat Commun. 2021;12:366.
Blagih J, Zani F, Chakravarty P, Hennequart M, Pilley S, Hobor S, Hock AK, Walton JB, Morton JP, Gronroos E, Mason S, Yang M, McNeish I, Swanton C, Blyth K, Vousden KH. Cancer-Specific Loss of p53 Leads to a Modulation of Myeloid and T Cell Responses. Cell reports. 2020;30:481-496.e6.
Campbell KJ, Blyth K Somatic base editing to model oncogenic drivers in breast cancer Lab Anim. 2020; 49: 115–116
Caraffini V, Geiger O, Rosenberger A, Hatzl S, Perfler B, Berg JL, Lim C, Strobl H, Kashofer K, Schauer S, Beham-Schmid C, Hoefler G, Geissler K, Quehenberger F, Kolch W, Athineos D, Blyth K, Wolfler A, Sill H, Zebisch A. Loss of RAF kinase inhibitor protein is involved in myelomonocytic differentiation and aggravates RAS-driven myeloid leukemogenesis. Haematologica. 2020;
Cheung EC, DeNicola GM, Nixon C, Blyth K, Labuschagne CF, Tuveson DA, Vousden KH. Dynamic ROS Control by TIGAR Regulates the Initiation and Progression of Pancreatic Cancer. Cancer cell. 2020; 37: 168-182
Dhayade S, Pietzke M, Wiesheu R, Tait-Mulder J, Athineos D, Sumpton D, Coffelt S, Blyth K, Vazquez A. Impact of Formate Supplementation on Body Weight and Plasma Amino Acids. Nutrients. 2020; 12(8):2181.
Lie ALM, Mevel R, Patel R, Blyth K, Baena E, Kouskoff V, Lacaud G. RUNX1 Dosage in Development and Cancer. Mol Cells. 2020; 43: 126-128
Loveridge CJ, Slater S, Campbell KJ, Nam NA, Knight J, Ahmad I, Hedley A, Lilla S, Repiscak P, Patel R, Salji M, Fleming J, Mitchell L, Nixon C, Strathdee D, Neilson M, Ntala C, Bryson S, Zanivan S, Edwards J, Robson CN, Goodyear CS, Blyth K, Leung HY. BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration. Oncogene. 2020; 39: 1797–1806
MacKenzie DJ, Robertson NA, Rather I, Reid C, Sendzikaite G, Cruickshanks H, McBryan T, Hodges A, Pritchard C, Blyth K, Adams PD. DNMT3B Oncogenic Activity in Human Intestinal Cancer Is Not Linked to CIMP or BRAFV600E Mutation. iScience. 2020;23:100838-100838.
Mevel R, Steiner I, Mason S, Galbraith LCA, Patel R, Fadlullah MZH, Ahmad I, Leung HY, Oliveira P, Blyth K, Baena E, Lacaud G. RUNX1 marks a luminal castration resistant lineage established at the onset of prostate development. eLife. 2020;9:e60225.
Millar R, Kilbey A, Remak SJ, Severson TM, Dhayade S, Sandilands E, Foster K, Bryant DM, Blyth K, Coffelt SB. The MSP-RON axis stimulates cancer cell growth in models of triple negative breast cancer. Molecular oncology. 2020;14: 1868-1880
Oizel K, Tait-Mulder J, Fernandez-de-Cossio-Diaz J, Pietzke M, Brunton H, Lilla S, Dhayade S, Athineos D, Blanco GR, Sumpton D, Mackay GM, Blyth K, Zanivan SR, Meiser J, Vazquez A. Formate induces a metabolic switch in nucleotide and energy metabolism. Cell death & disease. 2020;11:310.
Ran R, Harrison H, Syamimi Ariffin N, Ayub R, Pegg HJ, Deng W, Mastro A, Ottewell PD, Mason SM, Blyth K, Holen I, Shore P. A role for CBFbeta in maintaining the metastatic phenotype of breast cancer cells. Oncogene. 2020; 39: 2624–2637
Rooney N, Mason SM, McDonald L, Däbritz JHM, Campbell KJ, Hedley A, Howard S, Athineos D, Nixon C, Clark W, Leach JDG, Sansom OJ, Edwards J, Cameron ER, Blyth K RUNX1 is a driver of renal cell carcinoma correlating with clinical outcome Cancer Res. 2020;
Sweeney K, Cameron ER, Blyth K. Complex Interplay between the RUNX Transcription Factors and Wnt/β-Catenin Pathway in Cancer: A Tango in the Night. Molecules and cells. 2020; 43: 188-197
Zhang T, Bauer C, Newman AC, Uribe AH, Athineos D, Blyth K, Maddocks ODK. Polyamine pathway activity promotes cysteine essentiality in cancer cells. Nature Metabolism. 2020; 2:1062–1076
Hassan S, Purdie KJ, Wang J, Harwood CA, Proby CM, Pourreyron C, Mladkova N, Nagano A, Dhayade S, Athineos D, Caley M, Mannella V, Blyth K, Inman GJ, Leigh IM. A Unique Panel of Patient-Derived Cutaneous Squamous Cell Carcinoma Cell Lines Provides a Preclinical Pathway for Therapeutic Testing. International journal of molecular sciences. 2019; 20: 3428
Johnson SA, Ormsby MJ, McIntosh A, Tait SWG, Blyth K, Wall DM. Increasing the bactofection capacity of a mammalian expression vector by removal of the f1 ori. Cancer Gene Ther. 2019; 26: 183–194
Liko D, Mitchell L, Campbell KJ, Ridgway RA, Jones C, Dudek K, King A, Bryson S, Stevenson D, Blyth K, Strathdee D, Morton JP, Bird TG, Knight JRP, Willis AE, Sansom OJ. Brf1 loss and not overexpression disrupts tissues homeostasis in the intestine, liver and pancreas. Cell Death Differ. 2019; 26: 2535–2550
Rudzka DA, Spennati G, McGarry DJ, Chim YH, Neilson M, Ptak A, Munro J, Kalna G, Hedley A, Moralli D, Green C, Mason S, Blyth K, Mullin M, Yin H, Olson MF. Migration through physical constraints is enabled by MAPK-induced cell softening via actin cytoskeleton re-organization. Journal of cell science. 2019; 132:
Vande Voorde J, Ackermann T, Pfetzer N, Sumpton D, Mackay G, Kalna G, Nixon C, Blyth K, Gottlieb E, Tardito S. Improving the metabolic fidelity of cancer models with a physiological cell culture medium. Science Advances 2019; 5: eaau7314
Campbell KJ, Dhayade S, Ferrari N, Sims AH, Johnson E, Mason SM, Dickson A, Ryan KM, Kalna G, Edwards J, Tait SWG, Blyth K. MCL-1 is a prognostic indicator and drug target in breast cancer. Cell Death Dis 2018; 9:19
McCarroll CS, He W, Foote K, Bradley A, McGlynn K, Vidler F, Nixon C, Nather K, Fattah C, Riddell A, Bowman P, Elliott EB, Bell M, Hawksby C, MacKenzie SM, et al. Runx1 Deficiency Protects Against Adverse Cardiac Remodeling After Myocardial Infarction. Circulation 2018; 137: 57-70.
Meiser J, Schuster A, Pietzke M, Vande Voorde J, Athineos D, Oizel K, Burgos-Barragan G, Wit N, Dhayade S, Morton JP, Dornier E, Sumpton D, Mackay GM, Blyth K, Patel KJ, et al. Increased formate overflow is a hallmark of oxidative cancer. Nat Commun. 2018; 9: 1368.
Novo D, Heath N, Mitchell L, Caligiuri G, MacFarlane A, Reijmer D, Charlton L, Knight J, Calka M, McGhee E, Dornier E, Sumpton D, Mason S, Echard A, Klinkert K, et al. Mutant p53s generate pro-invasive niches by influencing exosome podocalyxin levels. Nat Commun 2018; 9: 5069.
Bulusu V, Tumanov S, Michalopoulou E, van den Broek NJ, MacKay G, Nixon C, Dhayade S, Schug ZT, Vande Voorde J, Blyth K, Gottlieb E, Vazquez A, Kamphorst JJ. Acetate Recapturing by Nuclear Acetyl-CoA Synthetase 2 Prevents Loss of Histone Acetylation during Oxygen and Serum Limitation. Cell Rep 2017; 18: 647-58
Dornier E, Rabas N, Mitchell L, Novo D, Dhayade S, Marco S, Mackay G, Sumpton D, Pallares M, Nixon C, Blyth K, Macpherson I, Rainero E, Norman JC. Glutaminolysis drives membrane trafficking to promote cancer invasion. Nat Commun 2017; 8: 2255.
Giampazolias E, Zunino B, Dhayade S, Bock F, Cloix C, Cao K, Roca A, Lopez J, Ichim G, Proics E, Rubio-Patino C, Fort L, Yatim N, Woodham E, Orozco S, Taraborrelli L, Peltzer N, Lecis D, Machesky L, Walczak H et al. Mitochondrial permeabilization engages NF-kappaB-dependent anti-tumour activity under caspase deficiency. Nat Cell Biol 2017; 19: 1116-29
Hernandez-Fernaud JR, Ruengeler E, Casazza A, Neilson LJ, Pulleine E, Santi A, Ismail S, Lilla S, Dhayade S, MacPherson IR, McNeish I, Ennis D, Ali H, Kugeratski FG, Al Khamici H, van den Biggelaar M, van den Berghe PV, Cloix C, McDonald L, Millan D et al. Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity. 2017 Nat Commun 8: 14206
Hock AK, Cheung EC, Humpton TJ, Monteverde T, Paulus-Hock V, Lee P, McGhee E, Scopelliti A, Murphy DJ, Strathdee D, Blyth K, Vousden KH. Development of an inducible mouse model of iRFP713 to track recombinase activity and tumour development in vivo. Sci Rep 2017; 7: 1837
Loveridge CJ, Mui EJ, Patel R, Tan EH, Ahmad I, Welsh M, Galbraith J, Hedley A, Nixon C, Blyth K, Sansom O, Leung HY. Increased T-cell Infiltration Elicited by Erk5 Deletion in a Pten-Deficient Mouse Model of Prostate Carcinogenesis. Cancer Res 2017; 77: 3158-68
Loveridge CJ, van 't Hof RJ, Charlesworth G, King A, Tan EH, Rose L, Daroszewska A, Prior A, Ahmad I, Welsh M, Mui EJ, Ford C, Salji M, Sansom O, Blyth K, Leung HY. Analysis of Nkx3.1:Cre-driven Erk5 deletion reveals a profound spinal deformity which is linked to increased osteoclast activity. Sci Rep 2017; 7: 13241
Maddocks ODK, Athineos D, Cheung EC, Lee P, Zhang T, van den Broek NJF, Mackay GM, Labuschagne CF, Gay D, Kruiswijk F, Blagih J, Vincent DF, Campbell KJ, Ceteci F, Sansom OJ, Blyth K, Vousden KH. Modulating the therapeutic response of tumours to dietary serine and glycine starvation. Nature 2017; 544: 372-6
Reid SE, Kay EJ, Neilson LJ, Henze AT, Serneels J, McGhee EJ, Dhayade S, Nixon C, Mackey JB, Santi A, Swaminathan K, Athineos D, Papalazarou V, Patella F, Roman-Fernandez A, ElMaghloob Y, Hernandez-Fernaud JR, Adams RH, Ismail S, Bryant DM et al. Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium. EMBO J 2017; 36: 2373-89
van Tuyn J, Jaber-Hijazi F, MacKenzie D, Cole JJ, Mann E, Pawlikowski JS, Singh Rai T, Nelson DM, McBryan T, Ivanov A, Blyth K, Wu H, Milling S, Adams PD. Oncogene-Expressing Senescent Melanocytes Upregulate Mhc Class Ii, A Candidate Melanoma Suppressor Function. J Invest Dermatol 2017; 137: 2197-207
Walton JB, Farquharson M, Mason S, Port J, Kruspig B, Dowson S, Stevenson D, Murphy D, Matzuk M, Kim J, Coffelt S, Blyth K, McNeish IA.
CRISPR/Cas9-derived models of ovarian high grade serous carcinoma targeting Brca1, Pten and Nf1, and correlation with platinum sensitivity. Sci Rep 2017;7: 16827
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Holen I, Speirs V, Morrissey B, Blyth K. In vivo models in breast cancer research: progress, challenges and future directions. Dis Model Mech 2017; 10: 359-71
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Liver cancer is the third most common cause of cancer-related death worldwide. It is becoming an increasing problem, particularly in the Western world, and its rates have trebled in Scotland in the last 20 years. Despite some improvements in outcomes for those patients in whom the disease is detected early, there remains a limited range of only minimally effective treatment options for the overwhelming majority of patients who have their disease detected at a later stage. Precision medicine offers the potential to target more effective therapies to individuals with different forms of this disease, across this highly heterogeneous cancer.
My group has been interested in studying the regenerative responses to injury and aberrant proliferative responses in cancer of hepatocytes, the principle functional cell of the liver. These cells show immense regenerative capacity but are also the source of the most common primary liver cancer, hepatocellular carcinoma (HCC).
We have described how these cells enter a state of shock, named senescence, in response to injury, and how preventing them from doing so can promote liver regeneration. We are also investigating how this same senescent state occurs during early cancer formation as an anti- cancer therapeutic target.
To further understand these processes, we have developed a state-of-the-art suite of genetically engineered models of HCC, which mimics key features of the human condition. This suite is based upon the range of genetic mutations which drive HCC across the spectrum of human disease. Cross comparing between the models and patients we are able to identify novel pathways for therapy and some drug combinations which are highly effective in our cancer models. Working with academic and industrial collaborators, we are using these avatar-like models to uncover and test novel therapies, which could be used to target precision medicine dependent on the underlying characteristics of tumours in different patients.
Read about Tom's collaboration with the University of Edinburgh's Centre for Statistics to improve early detection of liver cancer here.
Nehme J, Borghesan M, Mackedenski S, Bird TG, Demaria M. Cellular senescence as a potential mediator of COVID-19 severity in the elderly. Aging Cell. 2020:e13237.
Müller M, Bird TG, Nault J-C. The landscape of gene mutations in cirrhosis and hepatocellular carcinoma. J Hepatol. 2020; 72: 990-1002
Hughes DM, Berhane S, Degroot ECA, Toyoda H, Tada T, Kumada T, Satomura S, Nishida N, Kudo M, Kimura T, Osaki Y, Kolamunage-Dona R, Salvador RA, Bird TG, Fiñana MG, Johnson P. Serum Levels of Alpha Fetoprotein Increased More Than 10 Years Before Detection of Hepatocellular Carcinoma. Clin Gastroenterol Hepatol. 2020;19:162-170
Vizioli MG, Liu T, Miller KN, Robertson NA, Gilroy K, Lagnado AB, Perez-Garcia A, Kiourtis C, Dasgupta N, Lei X, Kruger PJ, Nixon C, Clark W, Jurk D, Bird TG, Passos JF, Berger SL, Dou Z, Adams PD. Mitochondria-to-nucleus retrograde signaling drives formation of cytoplasmic chromatin and inflammation in senescence. Genes & development. 2020; 34: 428-445
Amoros R, King R, Toyoda H, Kumada T, Johnson PJ, Bird TG. A continuous-time hidden Markov model for cancer surveillance using serum biomarkers with application to hepatocellular carcinoma. Metron. 2019;77:67-86.
Teo YV, Rattanavirotkul N, Olova N, Salzano A, Quintanilla A, Tarrats N, Kiourtis C, Muller M, Green AR, Adams PD, Acosta JC, Bird TG, Kirschner K, Neretti N, Chandra T. Notch Signaling Mediates Secondary Senescence. Cell Rep 2019; 27: 997-1007
Gay DM, Ridgway RA, Mueller M, Hodder MC, Hedley A, Clark W, Leach JD, Jackstadt R, Nixon C, Huels DJ, Campbell AD, Bird TG, Sansom OJ. Loss of BCL9/9l suppresses Wnt driven tumourigenesis in models that recapitulate human cancer. Nature communications 2019; 10: 723.
Bird TG, Muller M, Boulter L, Vincent DF, Ridgway RA, Lopez-Guadamillas E, Lu WY, Jamieson T, Govaere O, Campbell AD, Ferreira-Gonzalez S, Cole AM, Hay T, Simpson KJ, Clark W, et al. TGFbeta inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence. Sci Transl Med 2018; 10: eaan1230
Bird TG, Dimitropoulou P, Turner RM, Jenks SJ, Cusack P, Hey S, Blunsum A, Kelly S, Sturgeon C, Hayes PC, Bird SM. Alpha-Fetoprotein Detection of Hepatocellular Carcinoma Leads to a Standardized Analysis of Dynamic AFP to Improve Screening Based Detection. PLoS One 2016; 11: e0156801.
Lu WY, Bird TG, Boulter L, Tsuchiya A, Cole AM, Hay T, Guest RV, Wojtacha D, Man TY, Mackinnon A, Ridgway RA, Kendall T, Williams MJ, Jamieson T, Raven A, Hay DC, Iredale JP, Clarke AR, Sansom OJ, Forbes SJ. Hepatic progenitor cells of biliary origin with liver repopulation capacity. Nat Cell Biol 2015; 17: 971-83.
Bird TG, Lu WY, Boulter L, Gordon-Keylock S, Ridgway RA, Williams MJ, Taube J, Thomas JA, Wojtacha D, Gambardella A, Sansom OJ, Iredale JP, Forbes SJ. Bone marrow injection stimulates hepatic ductular reactions in the absence of injury via macrophage-mediated TWEAK signaling. PNAS 2013; 110: 6542-7.
Boulter L, Govaere O, Bird TG, Radulescu S, Ramachandran P, Pellicoro A, Ridgway RA, Seo SS, Spee B, Van Rooijen N, Sansom OJ, Iredale JP, Lowell S, Roskams T, Forbes SJ. Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease. Nature Medicine 2012; 18: 572-9.
Hsieh WC, Mackinnon AC, Lu WY, Jung J, Boulter L, Henderson NC, Simpson KJ, Schotanus B, Wojtacha D, Bird TG, Hay D, Medine C, Sethi T, Iredale JP, Forbes SJ. Galectin-3 regulates hepatic progenitor cell expansion during liver injury. Gut 2015; 64: 312-21.
Lorenzini S*, Bird TG*, Boulter L, Bellamy C, Samuel K, Aucott R, Clayton E, Andreone P, Bernardi M, Golding M, Alison MR, Iredale JP, Forbes SJ. Characterisation of a stereotypical cellular and extracellular adult liver progenitor cell niche in rodents and diseased human liver. Gut 2010; 59: 645-54. *Joint first authorship
2015: Certificate of completion of training: Gastroenterology and Hepatology
2012: Specialty Certificate, Gastroenterology, Royal College of Physicians
2011: PhD, Liver Regeneration by Hepatic Progenitor Cells, University of Edinburgh
2005: MRCP, Medicine, Royal College of Physicians
2003: MA, Physiological Sciences, Oxford University
2002: BM BCh, Medicine, Oxford University
1999: BA (1st Class), Physiological Sciences, Oxford University
2020: Reader, University of Edinburgh
2016: Senior Lecturer, University of Glasgow
2015: Honorary Consultant Hepatologist, Royal Infirmary of Edinburgh and Scottish Liver Transplant Unit
2013-2014: Hepatology Subspecialty Year, Royal Infirmary of Edinburgh
2011-2015: Clinical Lecturer in Hepatology, University of Edinburgh/Royal Infirmary of Edinburgh
2010-2011: ST Gastroenterology, Royal Infirmary of Edinburgh
2007-2010: Clinical Training Fellow, University of Edinburgh
2006-2007: Clinical Fellow, Royal Infirmary of Edinburgh
2005-2006: ST3 Renal and Liver Transplantation, Royal Infirmary of Edinburgh
2003-2005: Medical Senior House Officer, Western General Hospital, Edinburgh
2003: Surgical Pre-Registration House Officer, Royal United Hospital, Bath
2002-2003: Medical Pre-Registration House Officer, John Radcliffe Hospital, Oxford
UEG Rising Star award, 2019 – annual award by United European Gastroenterology
Francis Avery Jones Medal Winner, 2019 – annual award by the British Society of Gastroenterology
Andy Burroughs Young Investigator Award, 2015
British Society of Gastroenterology: Young Gastroenterologist of the Year - Clinical & Translational Science, 2015
Wellcome Trust Intermediate Clinical Fellowship, 2015
Wilfred Card Lectureship, 2014
Academy of Medical Sciences Start Grant for Clinical Lecturers, 2012
Sheila Sherlock Prize, 2011
ESOT Prize for scientific presentation, 2011
Anne Ferguson Prize, 2009
EASL travel bursary, 2009
Miss Urquart Charitable Trust Award, 2007
Wellcome Clinical Research Training Fellowship, 2007
BSG Travelling Fellowship, 2006
Griffith's Memorial Travelling Scholarship, 2001
Representative for the Queen's Award for Higher Education and Training, 2001
Martin Lawrence Memorial Scholarship, 2001
Paul Hayes Memorial Scholarship, 2000
Hobson Mann Oxford University Clinical Medical School Scholarship, 2000
Wronker dissertation prize, 1999
Garay OU, Ambühl LE, Bird TG, Barnes E, Irving WL, Walkley R, Rowe IA. Cost-effectiveness of HCC Surveillance Strategies in Patients With Compensated Liver Cirrhosis in the United Kingdom. Value Health. 2024.
Matchett KP, Wilson-Kanamori JR, Portman JR, Kapourani CA, Fercoq F, May S, Zajdel E, Beltran M, Sutherland EF, Mackey JBG, Brice M, Wilson GC, Wallace SJ, Kitto L, Younger NT, Dobie R, Mole DJ, Oniscu GC, Wigmore SJ, Ramachandran P, Vallejos CA, Carragher NO, Saeidinejad MM, Quaglia A, Jalan R, Simpson KJ, Kendall TJ, Rule JA, Lee WM, Hoare M, Weston CJ, Marioni JC, Teichmann SA, Bird TG, Carlin LM, Henderson NC. Multimodal decoding of human liver regeneration. Nature. 2024.
Krishna A, Meynert A, Kelder M, Ewing A, Sheraz S, Ferrer-Vaquer A, Grimes G, Becher H, Silk R, Semple CA, Kendall T, Hadjantonakis A-K, Bird T, Marsh JA, Hohenstein P, Wood AJ, Ozdemir DD. Mutational scanning reveals oncogenic CTNNB1 mutations have diverse effects on signalling and clinical traits. bioRxiv. 2023:2023.2011.2009.566307.
May S, Müller M, Livingstone CR, Skalka GL, Walsh PJ, Nixon C, Hedley A, Shaw R, Clark W, Voorde JV, Officer-Jones L, Ballantyne F, Powley IR, Drake TM, Kiourtis C, Keith A, Rocha AS, Tardito S, Sumpton D, Le Quesne J, Bushell M, Sansom OJ, Bird TG. Absent expansion of AXIN2+ hepatocytes and altered physiology in Axin2CreERT2 mice challenges the role of pericentral hepatocytes in homeostatic liver regeneration. J Hepatol. 2023; 78: 1028-1036
Moore M, Pardo L, Mitchell L, Schmidt T, May S, Mueller M, Strathdee D, Bryson S, Hodge K, Lilla S, Zanivan S, Waldron J, McGarry L, Peter-Durairaj R, Kanellos G, Nixon C, Ballantyne F, LeQuesne J, Sansom OJ, Bird T, Bushell M, Norman JC. The eIF4A2 negative regulator of mRNA translation promotes extracellular matrix deposition to accelerate hepatocellular carcinoma initiation. bioRxiv. 2023;Volume:2023.2008.2016.553544.
Villar VH, Allega MF, Deshmukh R, Ackermann T, Nakasone MA, Vande Voorde J, Drake TM, Oetjen J, Bloom A, Nixon C, Müller M, May S, Tan EH, Vereecke L, Jans M, Blancke G, Murphy DJ, Huang DT, Lewis DY, Bird TG, Sansom OJ, Blyth K, Sumpton D, Tardito S. Hepatic glutamine synthetase controls N5-methylglutamine in homeostasis and cancer. Nature Chemical Biology. 2023;19:292-300.
May S, Bird TG. How the liver keeps itself in shape. Elife. 2023;12.
Humpton TJ, Hall H, Kiourtis C, Nixon C, Clark W, Hedley A, Shaw R, Bird TG, Blyth K, Vousden KH. p53-mediated redox control promotes liver regeneration and maintains liver function in response to CCl(4). Cell Death Differ. 2022;29:514-526.
Humpton TJ, Hock AK, Kiourtis C, De Donatis M, Fercoq F, Nixon C, Bryson S, Strathdee D, Carlin LM, Bird TG, Blyth K, Vousden KH. A noninvasive iRFP713 p53 reporter reveals dynamic p53 activity in response to irradiation and liver regeneration in vivo. Sci Signal. 2022;15:eabd9099.
Leslie J, Mackey JBG, Jamieson T, Ramon-Gil E, Drake TM, Fercoq F, Clark W, Gilroy K, Hedley A, Nixon C, Luli S, Laszczewska M, Pinyol R, Esteban-Fabró R, Willoughby CE, Haber PK, Andreu-Oller C, Rahbari M, Fan C, Pfister D, Raman S, Wilson N, Müller M, Collins A, Geh D, Fuller A, McDonald D, Hulme G, Filby A, Cortes-Lavaud X, Mohamed N-E, Ford CA, Raffo Iraolagoitia XL, McFarlane AJ, McCain MV, Ridgway RA, Roberts EW, Barry ST, Graham GJ, Heikenwälder M, Reeves HL, Llovet JM, Carlin LM, Bird TG, Sansom OJ, Mann DA. CXCR2 inhibition enables NASH-HCC immunotherapy. Gut. 2022;10.1136/gutjnl-2021-326259:gutjnl-2021-326259.
Geh D, Leslie J, Rumney R, Reeves HL, Bird TG, Mann DA. Neutrophils as potential therapeutic targets in hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2022;19:257–273
Barthet VJA, Brucoli M, Ladds M, Nössing C, Kiourtis C, Baudot AD, O'Prey J, Zunino B, Müller M, May S, Nixon C, Long JS, Bird TG, Ryan KM. Autophagy suppresses the formation of hepatocyte-derived cancer-initiating ductular progenitor cells in the liver. Sci Adv. 2021;7: eabf9141
Burton A, Tataru D, Driver RJ, Bird TG, Huws D, Wallace D, Cross TJS, Rowe IA, Alexander G, Marshall A. Primary liver cancer in the UK: Incidence, incidence-based mortality, and survival by subtype, sex, and nation. JHEP Rep. 2021;3(2):100232.
Haq MI, Drake TM, Goh TL, Ahmed A, Forrest E, Barclay S, Gillespie R, Priest M, Evans J, Graham J, Ballantyne S, McMillan DC, Hayes PC, Bird TG, Stanley AJ. Effect of Hepatocellular Carcinoma Surveillance Programmes on Overall Survival in a Mixed Cirrhotic UK Population: A Prospective, Longitudinal Cohort Study. J Clin Med. 2021;10:2770
Kiourtis C, Wilczynska A, Nixon C, Clark W, May S, Bird TG. Specificity and off-target effects of AAV8-TBG viral vectors for the manipulation of hepatocellular gene expression in mice. Biol Open. 2021; 10: bio058678
Mackey JBG, McFarlane AJ, Jamieson T, Jackstadt R, Raffo-Iraolagoitia XL, Secklehner J, Cortes-Lavaud X, Fercoq F, Clarke W, Hedley A, Gilroy K, Lilla S, Vuononvirta J, Graham GJ, De Filippo K, Murphy DJ, Steele CW, Norman JC, Bird TG, Mann DA, Morton JP, Zanivan S, Sansom OJ, Carlin LM. Maturation, developmental site, and pathology dictate murine neutrophil function. bioRxiv. 2021.
Müller M, May S, Bird TG. Ploidy dynamics increase the risk of liver cancer initiation. Nat Commun. 2021;12:1896.
Hughes DM, Berhane S, Degroot ECA, Toyoda H, Tada T, Kumada T, Satomura S, Nishida N, Kudo M, Kimura T, Osaki Y, Kolamunage-Dona R, Salvador RA, Bird TG, Fiñana MG, Johnson P. Serum Levels of Alpha Fetoprotein Increased More Than 10 Years Before Detection of Hepatocellular Carcinoma. Clin Gastroenterol Hepatol. 2020;19:162-170
Leslie J, Macia MG, Luli S, Worrell JC, Reilly WJ, Paish HL, Knox A, Barksby BS, Gee LM, Zaki MYW, Collins AL, Burgoyne RA, Cameron R, Bragg C, Xu X, Chung GW, Brown CDA, Blanchard AD, Nanthakumar CB, Karsdal M, Robinson SM, Manas DM, Sen G, French J, White SA, Murphy S, Trost M, Zakrzewski JL, Klein U, Schwabe RF, Mederacke I, Nixon C, Bird T, Teuwen L-A, Schoonjans L, Carmeliet P, Mann J, Fisher AJ, Sheerin NS, Borthwick LA, Mann DA, Oakley F. c-Rel orchestrates energy-dependent epithelial and macrophage reprogramming in fibrosis. Nature Metabolism. 2020; 2:1350–1367
Müller M, Bird TG, Nault J-C. The landscape of gene mutations in cirrhosis and hepatocellular carcinoma. J Hepatol. 2020; 72: 990-1002
Vizioli MG, Liu T, Miller KN, Robertson NA, Gilroy K, Lagnado AB, Perez-Garcia A, Kiourtis C, Dasgupta N, Lei X, Kruger PJ, Nixon C, Clark W, Jurk D, Bird TG, Passos JF, Berger SL, Dou Z, Adams PD. Mitochondria-to-nucleus retrograde signaling drives formation of cytoplasmic chromatin and inflammation in senescence. Genes & development. 2020; 34: 428-445
Nehme J, Borghesan M, Mackedenski S, Bird TG, Demaria M. Cellular senescence as a potential mediator of COVID-19 severity in the elderly. Aging Cell. 2020:e13237.
Amoros R, King R, Toyoda H, Kumada T, Johnson PJ, Bird TG. A continuous-time hidden Markov model for cancer surveillance using serum biomarkers with application to hepatocellular carcinoma. Metron. 2019;77:67-86.
Drake TM, Bird TG. Editorial: simplifying screening for primary liver cancer - do the LCR1 and LCR2 tests hold the key? Alimentary pharmacology & therapeutics. 2019;49:612-613.
Gay DM, Ridgway RA, Mueller M, Hodder MC, Hedley A, Clark W, Leach JD, Jackstadt R, Nixon C, Huels DJ, Campbell AD, Bird TG, Sansom OJ. Loss of BCL9/9l suppresses Wnt driven tumourigenesis in models that recapitulate human cancer. Nature communications 2019; 10: 723.
Liko D, Mitchell L, Campbell KJ, Ridgway RA, Jones C, Dudek K, King A, Bryson S, Stevenson D, Blyth K, Strathdee D, Morton JP, Bird TG, Knight JRP, Willis AE, Sansom OJ. Brf1 loss and not overexpression disrupts tissues homeostasis in the intestine, liver and pancreas. Cell Death Differ. 2019; 26: 2535–2550
Muller M, Forbes SJ, Bird TG. Beneficial Noncancerous Mutations in Liver Disease. Trends in genetics. 2019; 35: 475-477
Teo YV, Rattanavirotkul N, Olova N, Salzano A, Quintanilla A, Tarrats N, Kiourtis C, Muller M, Green AR, Adams PD, Acosta JC, Bird TG, Kirschner K, Neretti N, Chandra T. Notch Signaling Mediates Secondary Senescence. Cell Rep 2019; 27: 997-1007
Bird TG, Muller M, Boulter L, Vincent DF, Ridgway RA, Lopez-Guadamillas E, Lu WY, Jamieson T, Govaere O, Campbell AD, Ferreira-Gonzalez S, Cole AM, Hay T, Simpson KJ, Clark W, et al. TGFbeta inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence. Sci Transl Med 2018; 10: eaan1230
Ferreira-Gonzalez S, Lu WY, Raven A, Dwyer B, Man TY, O'Duibhir E, Lewis PJS, Campana L, Kendall TJ, Bird TG, Tarrats N, Acosta JC, Boulter L, Forbes SJ. Paracrine cellular senescence exacerbates biliary injury and impairs regeneration. Nat Commun 2018; 9: 1020
Ogrodnik M, Miwa S, Tchkonia T, Tiniakos D, Wilson CL, Lahat A, Day CP, Burt A, Palmer A, Anstee QM, Grellscheid SN, Hoeijmakers JHJ, Barnhoorn S, Mann DA, Bird TG, Vermeij WP, Kirkland JL, Passos JF, von Zglinicki T, Jurk D. Cellular senescence drives age-dependent hepatic steatosis. Nat Commun 2017; 8: 15691
Kelly S, Bird TG. The Evolution of the Use of Serum Alpha-fetoprotein in Clinical Liver Cancer Surveillance. J Immunobiol 2017; 1. pii: 1000116
Bird TG, Dimitropoulou P, Turner RM, Jenks SJ, Cusack P, Hey S, Blunsum A, Kelly S, Sturgeon C, Hayes PC, Bird SM. Alpha-Fetoprotein Detection of Hepatocellular Carcinoma Leads to a Standardized Analysis of Dynamic AFP to Improve Screening Based Detection. PLoS One. 2016; 11: e0156801
Vidal V, Sacco S, Rocha AS, da Silva F, Panzolini C, Dumontet T, Thi Mai Phuong Doan, Shan J, Rak-Raszewska A, Bird T, Vainio S, Martinez A, Schedl A. The adrenal capsule is a signaling center controlling cell renewal and zonation through Rspo3. Genes Dev 2016; 30: 1389-94