Prof Tom Bird - Liver Cancer, Disease and Regeneration
Introduction
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.
EmailExposing liver cancer
Read about Tom's collaboration with the University of Edinburgh's Centre for Statistics to improve early detection of liver cancer here.
Lab Report
Key Publications
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
Biography
Education and qualifications
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
Appointments
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
Honours and awards
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
Recent Publications
2024
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.
Kiourtis C, Terradas-Terradas M, Gee LM, May S, Georgakopoulou A, Collins AL, O’Sullivan ED, Baird DP, Hassan M, Shaw R, Tan EH, Müller M, Engelmann C, Andreola F, Hsieh Y-C, Reed LH, Borthwick LA, Nixon C, Clark W, Hanson PS, Sumpton D, Mackay G, Suzuki T, Najumudeen AK, Inman GJ, Campbell A, Barry ST, Quaglia A, Morris CM, LeBeau FEN, Sansom OJ, Kirschner K, Jalan R, Oakley F, Bird TG. Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ. Nature Cell Biology. 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.
2023
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.
2022
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
2021
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.
2020
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.
2019
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
2018
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
2017
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
2016
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
Lab Members
Group Leader
Tom Bird
Honorary Consultant Hepatologist, University of Edinburgh and Royal Infirmary of Edinburgh
Wellcome Trust Intermediate Research Fellow
T.Bird@crukscotlandinstitute.ac.uk
I am a clinical academic and group leader of the Liver Cancer, Disease and Regeneration group. We have grown a highly collaborative team studying a number of models to understand how the liver functions and dysfunctions in cancer and how we can translate this understanding into therapy. This has impacted a number of ongoing clinical trials in patients. I am the Conference and Education lead for HCC-UK and sit on a number of steering/advisory committees externally. I love outdoor sports particularly anything in the water or on the hills.
Principal Scientific Officer
Stephanie May
S.May@crukscotlandinstitute.ac.uk
Hi, I am Steph, I was born in England, did my PhD in Wales and moved to Scotland as a postdoc. I am the Principal Scientific Officer in Prof Bird’s lab where I support the day-to-day operations of the group. I am fortunate to lead a team in my two research interests which focus on identifying therapies that can be used to prevent hepatocellular (liver) cancer and investigating the potential of stereotactic ablative radiotherapy and systemic therapy in the treatment of liver cancer. Outside of the lab you’ll most likely find me walking my dog along the canal or picking vegetables from my garden.
Research Scientists
Fiona Chalmers
F.Chalmers@crukscotlandinstitute.ac.uk
I am a postdoctoral scientist researching the effect of fatty diets on the development of liver cancer, as well as the impact of a fatty liver on the treatment of liver tumours. I have previously worked in a few other research labs in both my home country of Scotland and in the United States. I have prior research experience in other types of cancer, such as skin and nerve cancers, and in other aspects of molecular and cell biology such as cell stress response signalling pathways, protein folding biochemistry, and tissue development and differentiation. Outside of lab work, I enjoy video games, reading, and painting.
Anastasia Georgakopoulou
A.Georgakopoulou@crukscotlandinstitute.ac.uk
My name is Anastasia, and I am the lab’s Senior Scientific Officer. I hold an M.Sc. in Cancer Sciences and a Ph.D. in Cancer Research and Precision Oncology, both from the University of Glasgow. My current project aims to unveil transcriptomic and epigenetic dysregulation during tumour evolution, in liver carcinogenesis, as well as exploring novel therapeutic interventions targeting epigenetic regulators. Additionally, I support our lab in various laboratory techniques and procedures, troubleshooting, and data analysis. Outside the lab, I enjoy films, traveling, and a good board game challenge.
Megan Quince
M.Quince@crukscotlandinstitute.ac.uk
I am a Post Doctoral Researcher working on developing novel Liver Cancer therapies. I’m interested in further understanding liver cancer biology, specifically looking into immune modulation, inflammation and metabolism. I did the Cancer Sciences and Precision Oncology Masters at Glasgow University. I then went on to do my PhD at Glasgow, studying the characteristics and function of inflammation in Chronic Myeloid Leukaemia. I write and run a high fantasy Dungeons and Dragons adventure campaign for a group in my free time.
George Skalka
G.Skalka@crukscotlandinstitute.ac.uk
I am a Senior Scientific Officer in the Liver Cancer, Disease and Regeneration group. My project focuses on how liver cancer treatment can alter the tumour immune microenvironment. To interrogate this, I use a combination of murine liver cancer models, molecular biology, and bioinformatics analysis of large ‘omic datasets. In my spare time I enjoy playing hockey and coding.
Toshi Suzuki
T.Suzuki.2@crukscotlandinstitute.ac.uk
I am a postdoctoral researcher who is aspiring to be a group leader in the UK. Immune checkpoint inhibitors (ICIs) emerge as a very powerful therapy to advanced cancer patients, who used to have no treatment option. However, only a part of patients receives benefit from ICIs. My research focus is to understand why ICIs does not work in the majority of patients, and how we can make ICIs effective in more patients in future. T cells, macrophages and Wnt/β-catenin signalling are of my specific focuses. I enjoy working with many people and have been fortunate to collaborate with more than seven group leaders in the UK. I have also supervised 12 students (both master's and PhD), most of whom have pursued academic careers. Feel free to contact me if you are interested in my research.
Kyi Lai Yin Swe
K.YinSwe@crukscotlandinstitute.ac.uk
My name is Kyi Lai Yin Swe (Vanessa). I am a medical doctor, currently working in Tom’s group for the CRUK RadNet project. The study focuses on the effects of image-guided stereotactic ablative radiotherapy and systemic treatment in orthotopic transplant models. I am really dedicated to Oncology and Cancer Research. Personally, I really love baking and cooking.
Danis Thomas
D.Thomas@crukscotlandinstitute.ac.uk
I am a cell and molecular biologist, completing my MSci in Biochemistry from King's College London followed by my PhD from the University of Cambridge investigating centrosome loss-induced senescence. In Bird the lab, I work with Dr. Stephanie May to design precision prevention therapy strategies for Hepatocellular carcinoma using BH3-mimetics to treat our genetically engineered mouse models. I am particularly interested in how accumulation of fat in the liver can affect tumorigenesis as well as the effectiveness of preventative therapy. Outside work, I enjoy exploring the scenic nature of Scotland!
PhD Student
Clara Mullen
C.Mullen.3@research.gla.ac.uk
I am a PhD student from Glasgow, Scotland. Prior to joining CRUK Scotland Institute, I completed my undergraduate degree in Molecular and Cellular Biology and a Masters of Research (MRes) in Biomedical Science at the University of Glasgow. Here, I uncovered my interests in cancer studies leading me to pursue a career in cancer research. My PhD project aims to investigate the roles of stromal cell senescence in liver cancer development. Outside of work, I enjoy outdoor adventures, sports and exploring new places.
Prof Karen Blyth - In Vivo Cancer Biology
Introduction
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:
Lab Report
Key Publications
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
Biography
Education and qualifications
1997: PhD, University of Glasgow, Supervisors Ewan Cameron & Moyra Campbell
1991: BSc, Biochemistry (Honours), University of Glasgow
Appointments
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
Recent Publications
2024
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. EMBO Mol Med. 2024.
Cheung EC, Strathdee D, Stevenson D, Coomes J, Blyth K, Vousden KH. Regulation of ROS signaling by TIGAR induces cancer-modulating responses in the tumor microenvironment. Proc Natl Acad Sci U S A. 2024;121(50):e2416076121.
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.
Strathearn LS, Spender LC, Schoenherr C, Mason S, Edwards R, Blyth K, Inman GJ. C1orf106 (INAVA) Is a SMAD3-Dependent TGF-β Target Gene That Promotes Clonogenicity and Correlates with Poor Prognosis in Breast Cancer. Cells. 2024;13(18).
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.
Sansom O, Wells S, Kent D, Wood A, Pitceathly RDS, Isles A, Liu K, Twigg S, Blyth K, Chesler L. Better translation via collaboration: The MRC National Mouse Genetics Network. Cell Genom. 2024 Feb 14;4(2):100483.
2023
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
2022
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.
2021
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.
2020
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
2019
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
2018
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.
2017
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
Weigert M, Binks A, Dowson S, Leung EYL, Athineos D, Yu X, Mullin M, Walton JB, Orange C, Ennis D, Blyth K, Tait SWG, McNeish IA. RIPK3 promotes adenovirus type 5 activity. Cell Death and Disease 2017; 8: 3206
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
Morrissey B, Blyth K, Carter P, Chelala C, Jones L, Holen I, Speirs V. The Sharing Experimental Animal Resources, Coordinating Holdings (SEARCH) Framework: Encouraging Reduction, Replacement, and Refinement in Animal Research. PLoS Biol 2017 15: e2000719
Riggio AI, Blyth K. The Enigmatic Role of RUNX1 in Female-Related Cancers: Current Knowledge & Future Perspectives. FEBS J 2017; 284: 2345-62
Rooney N, Riggio AI, Mendoza-Villanueva D, Shore P, Cameron ER, Blyth K. Runx Genes in Breast Cancer and the Mammary Lineage. Adv Exp Med Biol 2017; 962: 353-68
2016
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.
Meiser J, Tumanov S, Maddocks O, Labuschagne CF, Athineos D, Van Den Broek N, Mackay GM, Gottlieb E, Blyth K, Vousden K, Kamphorst JJ, Vazquez A. Serine one-carbon catabolism with formate overflow. Science Advances 2: e1601273, 2016
Morrissey B, Blyth K, Carter P, Chelala C, Jones L, Holen I, Speirs V. SEARCHBreast: a new online resource to make surplus material from in vivo models of breast cancer visible and accessible to researchers. Breast Cancer Res 2016;18: 59.
Lab Members
Group Leader
Karen Blyth
Karen.Blyth@glasgow.ac.uk
I did my PhD at the University of Glasgow (too long ago!) studying cancer biology and oncogenic mechanisms of key cancer genes using mouse models of cancer – an interest I have continued to pursue throughout my career and since joining the CRUK Scotland Institute in 2009. What I enjoy most about my job is the fantastic people I work with and exciting collaborative science we do. I also co-lead the MRC National Mouse Genetic Network (NMGN) Cancer Cluster which is a UK team using complex genetic models of cancer to understand tumour complexity and how these might be used for better prediction of patient response to therapy. When I can escape work, I am happiest spending time with friends and family, exploring new places, being on remote Scottish beaches or chasing down the Aurora Borealis!
Associate Scientist
Kirsteen J. Campbell
K.Campbell@crukscotlandinstitute.ac.uk
As an Associate Scientist in the In Vivo Cancer Biology lab at CRUK Scotland Institute and an Honorary Senior Lecturer at University of Glasgow I lead research projects focussed on understanding the role of aberrant cell death in cancer development and response to therapy. With expertise in breast and prostate cancer, and interests extending to pancreatic, lung and brain cancer, I use in vivo and in vitro models to help identify new therapeutic approaches with the aim of making cancer treatments kinder and more effective.
An advocate of scientific outreach, you’ll find me happily discussing our research at open evenings, lab tours, work experience and cancer awareness events.
Research Scientist
Laura Martinez Escardo
L.Martinez-Escardo@crukscotlandinstitute.ac.uk
I am a postdoctoral scientist investigating the role of MCL-1 and other BCL-2 family proteins in prostate cancer at the In Vivo Cancer Biology group. I was born and raised in Terrassa, a city near Barcelona. My educational background is in Biomedical Sciences, with a master's degree in Biomedicine with a specialization in basic and translational research in cancer, and a Ph.D. in Biochemistry, Molecular Biology, and Biomedicine at Universitat Autònoma de Barcelona (UAB). My research background and interests are in cell death pathways and mechanisms of therapeutic resistance in cancer. Here at the Institute, I am interrogating how these cell death pathways are altered in prostate cancer and how reinstatement of cell death could be used to improve treatment for advanced prostate cancer. Outside of work, I like spending quality time with family and friends, and I find joy in engaging in sports activities such as hiking, cycling, climbing, and water sports. I do also like to have relaxation time listening to music, watching films, reading books, or cooking and learning new recipes from around the world.
Senior Scientific Officers
Nimrit Kaur
N.Kaur@crukscotlandinstitute.ac.uk
Driven by a deep passion for research, I am working as a Senior Scientific Officer investigating new potential radiosensitising agents in solid cancers. Originally from India, I moved to Glasgow in 2021 to pursue a Master of Research (MRes) in Biomedical Sciences specialising in Cancer Studies at the University of Glasgow. My initial role at CRUK SI began with my master’s project and evolved into a more extensive relationship, where I worked as a Scientific Officer in the Transgenic Technology unit to develop genetically modified mice using embryonic stem cells. Now, as part of Karen’s lab, I work with multiple cancer cell types in vitro and am honing my skills in the in vivo tumour models. Beyond the lab, I enjoy travelling, exploring new places (especially bakeries), and spending time outdoors.
Dale Watt
D.Watt@crukscotlandinstitute.ac.uk
I am a Senior Scientific Officer within the lab working predominantly on in vivo models of cancer. I work as part of the National Mouse Genetics Network in the Cancer Cluster group where we aim to develop and improve in vivo cancer models in order to align these better with human disease. I obtained my PhD at the CRUK Scotland institute in the field of Pancreatic Cancer and have an honours degree in Immunology from the University of Glasgow.
Graduate Students
Amy Lawlor
2317758l@student.gla.ac.uk
Matthew Winder
Prof Seth Coffelt – Immune Cells and Metastasis
Introduction
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.
Researchers discover key to 'supercharging' breast cancer treatment
Find out more about Seth's recent research in this article by STV News here.
Young Glasgow ovarian cancer survivor speaks out about life after the disease
Read the story from the Evening Times here.
Glasgow doctor reveals why he has taken on the city's fight against cancer
Read about Seth's background and move to Glasgow here.
Lab Report
pdf Coffelt Lab Report (84 KB)
Key Publications
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
Biography
Education and qualifications
2006: PhD, Interdisciplinary Program in Molecular & Cellular Biology, Tulane University, USA
2000: BA, Biology & Chemistry, Minors in Music & Global Studies, Drury University, USA
Appointments
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
Honours and awards
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
Current committee membership
Breast Cancer Now Grants Committee member
Recent Publications
2024
Churchhouse AMD, Billard CV, Suzuki T, Pohl SÖ G, Doleschall NJ, Donnelly K, Nixon C, Arends MJ, Din S, Kirkwood K, Marques Junior J, Von Kriegsheim A, Coffelt SB, Myant KB. Loss of DOCK2 potentiates Inflammatory Bowel Disease-associated colorectal cancer via immune dysfunction and IFNγ induction of IDO1 expression. Oncogene. 2024.
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.
Wiesheu R, Coffelt SB. From backstage to the spotlight: γδT cells in cancer. Cancer Cell. 2024.
2023
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.
2022
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.
2021
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.
2020
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;
2019
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
2018
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
2017
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
2016
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
Lab Members
Group Leader
Seth Coffelt
Seth.Coffelt@glasgow.ac.uk
Since I was a PhD student at Tulane University in New Orleans, Louisiana, I have been interested in how non-cancerous cells within tumors and metastatic lesions contribute to cancer progression. Throughout my research career, I’ve had the opportunity to study mesenchymal stromal cells, macrophages, neutrophils, and T cells in mouse models of cancer, while living in some really fantastic places. After leaving America, I moved to Sheffield, England, then to Amsterdam where I worked at the Netherlands Cancer Institute (NKI). My lab at the CRUK Scotland Institute – where I’ve been since 2016 – has focused on the functions of gamma delta T cells during cancer evolution. This work we do with the help of many colleagues in Glasgow and around the world. I’m a people person so collaborating with other researchers gives me a lot of joy. At the weekends, I chase the kids around and frequent nice restaurants.
Postdoctoral Scientists
Nadia Iqbal
Nadia.Iqbal@glasgow.ac.uk
I studied biomedicine at the University of Manchester after which I completed my MRes in Translational Medicine, it was during this time that my interest in cancer research was cemented. I went on to work at the CRUK Manchester Institute as a scientific officer in the clinical and experimental pharmacology group investigating circulating tumour cells in various clinical trials after which I spent some time in the UoM functional genomics group. In my Ph.D. and first postdoc at Lancaster University I investigated the role of fat associated lymphoid clusters in the pleural cavity in the context of the inflammatory microenvironment in response to fibres. Currently I am a postdoc in Professor Seth Coffelt’s group, I am particularly interested in the tumour immune microenvironment and unlocking immunotherapeutic targets in cancer. During my spare time I like to read, cook, shop, visit nice restaurants, and holiday!
Abhiram Mallu
AbhiramCharanTej.Mallu@glasgow.ac.uk
I am a postdoctoral researcher interested in understanding the paradoxical role of T cells in tumour progression and suppression. My current research investigates how gamma-delta T cells in the pancreatic tumour microenvironment instigate metastasis in the KPC model. During my PhD in India, I studied the effect of healthy and impaired glucose metabolism on lymphocyte trafficking and neo-vascularization. I am an enthusiastic teacher, and I aspire to lead my own research group in the future. When I am not experimenting with immune cells, I like to experiment with food, explore unfamiliar places, and enjoy reading, music, and movies.
Natalie Phinney
N.Phinney@crukscotlandinstitute.ac.uk
I am a postdoctoral research scientist investigating the influence of gamma-delta T cells on pancreatic cancer primary tumor survival and progression. Originally from Basingstoke, UK, I completed my PhD in Cancer Biology at UT Southwestern Medical Center in Dallas, TX USA, developing a tumor-targeting fusion protein. I also have a JD (law) degree from the University of Tennessee, USA. When not in lab, I enjoy riding horses, running, and taking my three kids to the country park.
Toshi Suzuki
T.Suzuki.2@crukscotlandinstitute.ac.uk
Orchid LinkedIn X
I am a postdoctoral researcher who is aspiring to be a group leader in the UK. Immune checkpoint inhibitors (ICIs) emerge as a very powerful therapy to advanced cancer patients, who used to have no treatment option. However, only a part of patients receives benefit from ICIs. My research focus is to understand why ICIs does not work in the majority of patients, and how we can make ICIs effective in more patients in future. T cells, macrophages and Wnt/β-catenin signalling are of my specific focuses. I enjoy working with many people and have been fortunate to collaborate with more than seven group leaders in the UK. I have also supervised 12 students (both master's and PhD), most of whom have pursued academic careers. Feel free to contact me if you are interested in my research.
Principal Scientific Officer
Heather Spence
H.Spence@crukscotlandinstitute.ac.uk
I am currently working as the principal scientific officer in Prof Seth Coffelt’s lab investigating the role of role of gamma delta T cells in pancreatic and colon cancer. My scientific journey started with my PhD at Glasgow University with Prof Malcolm Kennedy, where we cloned the major Allergen of Ascaris Lumbricoides. I then had the amazing opportunity to work as a postdoctoral fellow at the Netherlands institute for Brain Research studying the role of frame shift mutations in Alzheimer’s disease. Returning to Glasgow, I pursued a postdoctoral position with Prof Brad Ozanne at the Beatson Institute, studying AP-1 regulated genes in invasion of tumour cells and then with Prof Steve Winder at the University of Glasgow working on actin binding proteins in muscular dystrophy. Following this, I worked for 17 years with Prof Laura Machesky, as the lab’s principal scientific officer studying actin cytoskeleton in metastasis and tumour microenvironment.
Clinical Research Fellow
David Hamilton
3068567H@student.gla.ac.uk
I am a higher speciality trainee in General Surgery in the West of Scotland, currently in my first year of PhD under the supervision of Prof Seth Coffelt. My current research investigates the role of Gamma Delta T cells in pancreatic cancer. When I am not in the lab or the hospital I like to spend my time travelling, attending live music events or on the golf course.
PhD Students
Federico Lupo
2188322l@student.gla.ac.uk
@ImmunoWolf
I am a PhD student in Coffelt’s lab exploring the role of T cells residing in the intestines (IEL) during colon cancer initiation. Originally from Sicily, I’d completed my Integrated Master’s in Immunology at the University of Glasgow with a one-year placement in the lab of Dr Molly Ingersoll in Paris. Here, while studying the prostate immune response against gram-negative and gram-positive bacteria during urinary tract infections, I made an important discovery: Immunology is my passion! Be it in cancer or infection, I’m in awe of how hundreds of cell responses are finely tuned to avoid, contain, or repress the challenge! Outside of work, I enjoy working out, reading, and travelling to new places.
Febby Nurdiya Ningsih
3057295f@student.gla.ac.uk
All the way from Indonesia to start my PhD journey in Seth Coffelt's lab and study Cancer Associated-Lymphopenia (CAL), particularly in a liver cancer model. I did previous research on an anti-inflammatory compound isolated from Japanese herb and completed my MSc in Japan. Then, I worked in the National Research and Innovation Agency (BRIN), Indonesia to develop monoclonal antibody and marine-based anti-cancer drug candidates. This dynamically changing research journey made me realize that I pretty much enjoyed every challenge of science progression. Moreover, I have always been interested in how immune cells play their roles during disease development, which in the future, I wish to focus more on cancer cases. Out of the lab, I love to do solo-travelling, hiking, and café-hopping.
Master's Students
Lewis Pennie
2623778p@student.gla.ac.uk
I am a 4th year Immunology MSci student from the University of Glasgow, and I am undergoing my work placement year carrying out research within colorectal cancer. I am interested in the role that the immune system plays within cancer, specifically how immune cells such as γδ T Cells can be pro-tumorigenic and anti-tumorigenic. Out with the lab and university I like to Mountain Bike, listen to and play music, play football, and golf.
Former Lab Members
Muhammad Aslam
Sarah Edwards (Senior Scientist, Takeda)
Kyla Foster (University of Colorado, Boulder, USA)
Anastasia Georgakopoulou
Teresa Glauner
Wilma Hoevenaar
Anna Kilbey
Rhona Millar
Erin Morris (Department Chair of Biology & Chemistry, Baker University, Baldwin City, Kansas, USA)
Anna Pidoux
Damiano Rami
Sarah Jane Remak
Elizabeth Thompson
Josip Vrancic
Robert Wiesheu
Prof Jen Morton - Preclinical Pancreatic Cancer
Introduction
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:
- New trick for 'old' drug brings hope for pancreatic cancer patients
- Scientists tear down pancreatic cancer's defences
Other funding:
Lab Report
pdf Morton Lab Report (127 KB)
Key Publications
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.
Biography
Education and qualifications
2001: PhD, Veterinary Pathology, University of Glasgow
1998: BSc (Hons. 1st), Medical Biochemistry, University of Glasgow
Appointments
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
Recent Publications
2024
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.
Fey SK, Najumudeen AK, Watt DM, Millett LM, Ford CA, Gilroy K, Simpson RJ, McLay K, Upstill-Goddard R, Chang D, Clark W, Nixon C, Birch JL, Barry ST, Morton JP, Campbell AD, Sansom OJ. KRAS Loss of Heterozygosity Promotes MAPK-Dependent Pancreatic Ductal Adenocarcinoma Initiation and Induces Therapeutic Sensitivity to MEK Inhibition. Cancer Res. 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).
2023
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.
2022
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.
2021
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
2020
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;
2019
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.
2018
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.
2017
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
2016
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.
Prof David Bryant - Epithelial Polarity
Introduction
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 loose 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 regulators 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.
Cell scientist to watch − David Bryant
Click here to read David's interview with the Journal of Cell Science.
Click here to read David’s perspective article on LGBT+ visibility in leadership.
Click here to read David’s essay on using your voice to stand up for diversity
Other funding:
Lab Report
pdf Bryant Lab Report (623 KB)
Research Highlights
- Loss of PTEN in High-Grade Serous Ovarian Cancers unleashes a pro-invasive module, consisting of an ARF GTPase module that governs endocytic recycling of pro-invasive integrins (EMBO J, 2023)
- The modality through which prostate tumours metastasise is regulated by surface levels of the adhesion protein N-cadherin, controlled by the ARF3 GTPase (JCB, 2023)
- The sialomucin Podocalyxin drives metastasis by acting as a decoy receptor to remove the function of otherwise invasion-inhibiting proteins (Science Advances 2023)
- Development of a machine-learning and live-imaging based methodology for detecting heterogeneity in 3D culture (Nat Comms, 2022)
- An ARF GTPase pathway amplified in cancer patients controls key lipid (phosphatidylinositol-phosphate) signalling to drive metastasis (Nat Comms, 2021)
- Identification of the key lipid (phosphatidylinositol-phosphate) metabolic pathways that control the formation of an apical surface. This defined that PI(3,4)P2 is a determinant of apical identity (Nat Comms, 2018)
Key Recent Publications
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.
Biography
Education and qualifications
2006: PhD, University of Queensland, Australia, Supervisor Jennifer Stow
2002: BSc (Hons) Class I, University of Queensland, Australia
Appointments
2024-present: Professor, School of Cancer Sciences, University of Glasgow
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
Professional committee membership
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
Honours and awards
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'
Recent Publications
2023
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.
2022
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
2021
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
2020
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
2019
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
2018
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:
2017
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
2016
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,
Lab Members
Group Leader
David Bryant
David.Bryant@glasgow.ac.uk
I was a PhD student at the University of Queensland, Australia, studying how growth factor receptors control cell-cell adhesion and migration. I followed this as a Postdoctoral Fellow at University of California, San Francisco studying how cells build apical surfaces. I established the research group at the CRUK Scotland Institute in 2014. My interests are in how groups of cells assemble into tissue and how the rules for this in cancer are changed. I'm also a strong advocate for LGBT equality, and in working to make the workplace open and accepting to all. Outside of work, you'll find me obsessed by cute dogs, playing piano, and going to concerts.
Laboratory Manager
Emma Sandilands
E.Sandilands@crukscotlandinstitute.ac.uk
As a PhD student at the Beatson Institute, Glasgow and a Postdoctoral Fellow at the Edinburgh Cancer Research Centre I investigated the various roles that Src and FAK tyrosine kinases play in cancer. I am currently a Laboratory Manager, where I use high-content microscopy, computational image analysis and molecular biology to study the invasion and metastasis of prostate and colon cancer in 3D. Outside of the lab you’ll find me spending time with my family and trying to keep my houseplants alive.
Postdoctoral Scientist
Archana Katoch
Archana.Katoch@glasgow.ac.uk
I joined the Postdoctoral researcher position at the Beatson Institute in 2021, following my PhD where I investigated the role of Epithelial-mesenchymal transition in cancer growth and therapeutic resistance. In my current role, I am investigating the mechanisms that control colorectal cancer growth and metastasis, and optimising experimental systems to aid my research. When not in the lab, I love to explore the breathtaking Scottish landscapes and going for long walks (in the hopes that I get to pet a lot of dogs).
PhD Students
Amy Bryson
2030391b@student.gla.ac.uk
As a PhD student my project focuses on investigating effects on cell growth and morphology upon manipulation of PIP metabolism enzymes expression in colon cancer. I use both in vitro and bioinformatic approaches in my work. For four years before beginning my PhD I worked in drug discovery carrying out high-throughput assay development and drug screening. Outside of the lab I dabbled in several crafts and always have at least one on the go. Between these I am not busy enough so you will often find me doing Scottish Country Dancing.
Yuanhao Lyu
3027377L@student.gla.ac.uk
I joined Professor David Bryant’s lab in 2024 as a PhD student, where I am currently focused on investigating the role of the PIP metabolism pathway in colorectal cancer metastasis. My research aims to identify key molecules within this pathway that may either promote or inhibit metastasis, with the potential to develop them into biomarkers or therapeutic targets. To achieve this, a variety of cutting-edge techniques, including gene editing, genetically modified mouse models, organoids, live cell imaging, and flow cytometry will be employed. Outside of the lab, I enjoy skating and traveling.
Senior Scientific Officer
Sonia Rolo
2507183R@student.gla.ac.uk
I was a PhD student at the CRUK SI, now transferred into my new Senior Scientific Officer position. I am using high-content microscopy and super resolution imaging to assess and optimize tools to elucidate phosphoinositide localisation in 3-dimensional organoid cultures models of colon cancer. Outside of work, you will find me practicing the Arts, currently focussed on poetry and watercolour paintings.
Master's Student
Nathan O'Donnell
2652015o@student.gla.ac.uk
I am currently undergoing a placement year at the CRUK SI as part of my MSci in Molecular and Cellular Biology (with biotechnology) at the University of Glasgow. I started my year placement in June 2024, and my project focuses on screening compounds which inhibit different proteins in the PI3K/Akt signalling pathway in PTEN-null KPN organoids. Outside of work, I enjoy playing most sports, but especially football and golf (when the ball goes straight!).
Former Lab Members
Dr Mohammed Mansour, Postdoctoral Fellow (Now: Senior Lecturer, London Southbank University)
Dr Narissa Parry, PhD Student (Now: Vertex Pharmaceuticals)
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: Memorial Sloan Kettering Cancer Center)
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