Prof Sara Zanivan - Tumour Microenvironment and Proteomics
Introduction
Discovery Research
Cancer associated fibroblasts (CAFs) have emerged as a promising therapeutic target in cancer because it is now well established that they actively contribute to tumour pathology. CAFs are a unique cell type in that they are highly secretory, and their secretome dictates the structure of a tumour and influences the behaviour of cancer cells and other cell types.
With our research we want to understand the molecular mechanisms through which CAFs alter the tumour microenvironment (TME) to influence cancer aggressiveness and resistance to therapy.
High-grade serous ovarian cancer and triple negative breast cancer are the major focus of our research because there are limited therapies against the cancer cells of these tumour types. However, CAFs are highly abundant in these tumours, and our overarching goal is to find ways to target CAFs in combination with other anti-cancer therapies to improve survival of cancer patients.
In the last few years, our work has described unprecedented ways through which CAFs create a TME that supports tumour invasion and metastasis by altering the structure of the extracellular matrix (ECM), and tumour blood vessels' and cancer cells' functions. A major focus of our on-going research is the metabolism of CAFs. We have found that cell metabolism is a major epigenetic regulator of CAF functions and that it can influence the translation of pro-tumorigenic ECM proteins. Our on-going research aims to investigate these aspects further and to understand how targeting specific metabolic pathways affects the composition and structure of the ECM and the immune-TME, and whether it can be exploited to halt cancer progression and improve effectiveness of conventional therapeutic treatments.
Our research is unique in that we mostly work with patient-derived cells that we generate in the lab from tissues that patients kindly donate to research. We also work with pre-clinical models relevant for ovarian and breast cancer. Moreover, because of our established expertise in mass spectrometry (MS)-proteomics, we develop tailored technology to study CAF biology, including their crosstalk signalling with other cell types in co-cultures in vitro and their metabolism in vivo.
Clinical Research
Recently, we have joined the effort to improve early detection of cancer in patients, since detecting cancer at an early stage can dramatically increase opportunities for curative intervention. To tackle this challenge, we are developing novel MS proteomic-based technology for biomarker discovery in body fluids. This research is funded by the CRUK Early Detection and Diagnosis Research scheme.
EmailThis research is funded by the Stand Up to Cancer campaign for Cancer Research UK
Lab Report
pdf Zanivan Lab Report (102 KB)
Key Publications
Kugeratski FG, Atkinson SJ, Neilson LJ, Lilla S, Knight JRP, Serneels J, Juin A, Ismail S, Bryant DM, Markert EK, Machesky LM, Mazzone M, Sansom OJ, Zanivan S. Hypoxic cancer-associated fibroblasts increase NCBP2-AS2/HIAR to promote endothelial sprouting through enhanced VEGF signaling. Science signaling 2019; 12: eaan8247
van der Reest J, Lilla S, Zheng L*, Zanivan S*, Gottlieb E*. Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress. Nat Commun. 2018; 9: 1581
Hernandez-Fernaud JR, Ruengeler E, Casazza A, Neilson LJ, Pulleine E, Santi A, Ismail S, Lilla S, Dhayade S, MacPherson IR, McNeish I, Ennis D, Ali H, Kugeratski FG, Al Khamici H, van den Biggelaar M, van den Berghe PV, Cloix C, McDonald L, Millan D et al. Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity. Nat Commun 2017; 8: 14206
Reid SE, Kay EJ, Neilson LJ, Henze AT, Serneels J, McGhee EJ, Dhayade S, Nixon C, Mackey JB, Santi A, Swaminathan K, Athineos D, Papalazarou V, Patella F, Roman-Fernandez A, ElMaghloob Y, Hernandez-Fernaud JR, Adams RH, Ismail S, Bryant DM et al. Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium. EMBO J. 2017; 36: 2373-89
Biography
Education and qualifications
2006: PhD, Complex Systems Applied to Post Genomic Biology, University of Torino, Italy
2002: Master in Bioinformatics, University of Torino, Italy
2001: MS in Biology, University of Torino, Italy
Appointments
2010-present: Group Leader, CRUK Scotland Institute
2014-present Head of Proteomics Advanced Technology, CRUK Scotland Institute
2007-2010: Postdoctoral Fellow with Matthias Mann, Max Planck Institute of Biochemistry, Martinsried, Germany
2002-2006: PhD Student with Guido Serini and Federico Bussolino, Candiolo Cancer Institute IRCCS, Torino, Italy
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.
Dawson A, Zarou MM, Prasad B, Bittencourt-Silvestre J, Zerbst D, Himonas E, Hsieh YC, van Loon I, Blanco GR, Ianniciello A, Kerekes Z, Krishnan V, Agarwal P, Almasoudi H, McCluskey L, Hopcroft LEM, Scott MT, Baquero P, Dunn K, Vetrie D, Copland M, Bhatia R, Coffelt SB, Tiong OS, Wheadon H, Zanivan S, Kirschner K, Helgason GV. Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche. Nat Commun. 2024;15(1):1090.
Gounis M, Campos AV, Shokry E, Mitchell L, Dornier E, Rooney N, Dhayade S, Pardo L, Moore M, Novo D, Mowat J, Jamieson C, Kay E, Zanivan S, Nixon C, Macpherson I, Tardito S, Sumpton D, Blyth K, Norman JC, Clarke CJ. Metabolic adaptations of micrometastases alter EV production to generate invasive microenvironments. bioRxiv. 2024:2024.2005.2012.593552.
Mahmood M, Liu EM, Shergold AL, Tolla E, Tait-Mulder J, Huerta-Uribe A, Shokry E, Young AL, Lilla S, Kim M, Park T, Boscenco S, Manchon JL, Rodríguez-Antona C, Walters RC, Springett RJ, Blaza JN, Mitchell L, Blyth K, Zanivan S, Sumpton D, Roberts EW, Reznik E, Gammage PA. Mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade response in melanoma. Nat Cancer. 2024.
Sanchez-Lopez I, Orantos-Aguilera Y, Pozo-Guisado E, Alvarez-Barientos A, Lilla S, Zanivan S, Lachaud C, Martin-Romero FJ. STIM1 translocation to the nucleus protects cells from DNA damage. Nucleic Acids Res. 2024.
Santi A, Kay EJ, Neilson LJ, McGarry L, Lilla S, Mullin M, Paul NR, Fercoq F, Koulouras G, Rodriguez Blanco G, Athineos D, Mason S, Hughes M, Thomson G, Kieffer Y, Nixon C, Blyth K, Mechta-Grigoriou F, Carlin LM, Zanivan S. Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. Sci Signal. 2024;17(827):eade0580.
Singh SP, Smyth DJ, Cunningham KT, Mukundan A, Byeon CH, Hinck CS, White MPJ, Ciancia C, Wąsowska N, Sanders A, Jin R, White RF, Lilla S, Zanivan S, Schoenherr C, Inman GJ, van Dinther M, Ten Dijke P, Hinck AP, Maizels RM. The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding. EMBO Rep. 2024.
Vringer E, Heilig R, Riley JS, Black A, Cloix C, Skalka G, Montes-Gómez AE, Aguado A, Lilla S, Walczak H, Gyrd-Hansen M, Murphy DJ, Huang DT, Zanivan S, Tait SW. Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response. EMBO J. 2024.
Whitelaw JA, Lilla S, Nikolaou S, Tweedy L, Fort L, Paul NR, Zanivan S, Gadegaard N, Insall RH, Machesky LM. CYRI-B loss promotes enlarged mature focal adhesions and restricts microtubule and ERC1 access to the cell leading edge. bioRxiv. 2024:2024.2003.2026.586838.
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.
Altea-Manzano P, Doglioni G, Liu Y, Cuadros AM, Nolan E, Fernández-García J, Wu Q, Planque M, Laue KJ, Cidre-Aranaz F, Liu XZ, Marin-Bejar O, Van Elsen J, Vermeire I, Broekaert D, Demeyer S, Spotbeen X, Idkowiak J, Montagne A, Demicco M, Alkan HF, Rabas N, Riera-Domingo C, Richard F, Geukens T, De Schepper M, Leduc S, Hatse S, Lambrechts Y, Kay EJ, Lilla S, Alekseenko A, Geldhof V, Boeckx B, de la Calle Arregui C, Floris G, Swinnen JV, Marine JC, Lambrechts D, Pelechano V, Mazzone M, Zanivan S, Cools J, Wildiers H, Baud V, Grünewald TGP, Ben-David U, Desmedt C, Malanchi I, Fendt SM. A palmitate-rich metastatic niche enables metastasis growth via p65 acetylation resulting in pro-metastatic NF-κB signaling. Nat Cancer. 2023; 4: 344–364
Kugeratski F, LeBleu V, Dowlatshahi D, Sugimoto H, Arian K, Fan Y, Huang L, Wills D, Lilla S, Hodge K, Zanivan S, McAndrews K, Kalluri R. Engineered immunomodulatory extracellular vesicles derived from epithelial cells acquire capacity for positive and negative T cell co-stimulation in cancer and autoimmunity. bioRxiv. 2023:2023.2011.2002.565371.
Mahmood M, Liu EM, Shergold AL, Tolla E, Tait-Mulder J, Uribe AH, Shokry E, Young AL, Lilla S, Kim M, Park T, Manchon JL, Rodriguez-Antona C, Walters RC, Springett RJ, Blaza JN, Zanivan S, Sumpton DA, Roberts EW, Reznik E, Gammage PA. Tumour mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade. bioRxiv. 2023;Volume:2023.2003.2021.533091.
Moore M, Pardo L, Mitchell L, Schmidt T, May S, Mueller M, Strathdee D, Bryson S, Hodge K, Lilla S, Zanivan S, Waldron J, McGarry L, Peter-Durairaj R, Kanellos G, Nixon C, Ballantyne F, LeQuesne J, Sansom OJ, Bird T, Bushell M, Norman JC. The eIF4A2 negative regulator of mRNA translation promotes extracellular matrix deposition to accelerate hepatocellular carcinoma initiation. bioRxiv. 2023;Volume:2023.2008.2016.553544.
Nikolatou K, Sandilands E, Román-Fernández A, Cumming EM, Freckmann E, Lilla S, Buetow L, McGarry L, Neilson M, Shaw R, Strachan D, Miller C, Huang DT, McNeish IA, Norman JC, Zanivan S, Bryant DM. PTEN deficiency exposes a requirement for an ARF GTPase module for integrin-dependent invasion in ovarian cancer. The EMBO Journal. 2023;n/a:e113987.
Román-Fernández A, Mansour MA, Kugeratski FG, Anand J, Sandilands E, Galbraith L, Rakovic K, Freckmann EC, Cumming EM, Park J, Nikolatou K, Lilla S, Shaw R, Strachan D, Mason S, Patel R, McGarry L, Katoch A, Campbell KJ, Nixon C, Miller CJ, Leung HY, Le Quesne J, Norman JC, Zanivan S, Blyth K, Bryant DM. Spatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function. Sci Adv. 2023;9:eabq1858.
Santi A, Kay EJ, Neilson LJ, McGarry L, Lilla S, Mullin M, Paul NR, Fercoq F, Koulouras G, Blanco GR, Athineos D, Mason S, Hughes M, Kieffer Y, Nixon C, Blyth K, Mechta-Grigoriou F, Carlin LM, Zanivan S. Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function. bioRxiv. 2023;Volume:2023.2001.2013.523951.
Schmidt T, Dabrowska A, Waldron JA, Hodge K, Koulouras G, Gabrielsen M, Munro J, Tack DC, Harris G, McGhee E, Scott D, Carlin Leo M, Huang D, Le Quesne J, Zanivan S, Wilczynska A, Bushell M. eIF4A1-dependent mRNAs employ purine-rich 5’UTR sequences to activate localised eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation. Nucleic Acids Research. 2023; 51: 1859–1879
Singh SP, Smyth DJ, Cunningham K, Mukundan A, Byeon C-H, Hinck CS, White MPJ, Ciancia C, Wosowska N, Sanders A, Jin R, Lilla S, Zanivan S, Schoenherr C, Inman G, Dinther Mv, Dijke Pt, Hinck AP, Maizels RM. The helminth TGF-β mimic TGM4 is a modular ligand that binds CD44, CD49d and TGF-β receptors to preferentially target myeloid cells. bioRxiv. 2023:2023.2011.2013.566701.
Subramaniam G, Schleicher K, Kovanich D, Zerio A, Folkmanaite M, Chao YC, Surdo NC, Koschinski A, Hu J, Scholten A, Heck AJR, Ercu M, Sholokh A, Chan Park K, Klussmann E, Meraviglia V, Bellin M, Zanivan S, Hester S, Mohammed S, Zaccolo M. Integrated Proteomics Unveils Nuclear PDE3A2 as a Regulator of Cardiac Myocyte Hypertrophy. Circ Res. 2023;132:828–848
Kay EJ, Zanivan S. Bicarbonate transport as regulator of anti-tumour immunity in pancreatic cancer. Mol Oncol. 2023;17:541-544
Kay EJ, Zanivan S, Rufini A. Proline metabolism shapes the tumor microenvironment: from collagen deposition to immune evasion. Curr Opin Biotechnol. 2023:103011.
2022
Baudot AD, Wang VM, Leach JD, O'Prey J, Long JS, Paulus-Hock V, Lilla S, Thomson DM, Greenhorn J, Ghaffar F, Nixon C, Helfrich MH, Strathdee D, Pratt J, Marchesi F, Zanivan S, Ryan KM. Glycan degradation promotes macroautophagy. Proc Natl Acad Sci U S A. 2022;119(26):e2111506119.
Blomme A, Peter C, Mui E, Rodriguez Blanco G, An N, Mason LM, Jamieson LE, McGregor GH, Lilla S, Ntala C, Patel R, Thiry M, Kung SHY, Leclercq M, Ford CA, Rushworth LK, McGarry DJ, Mason S, Repiscak P, Nixon C, Salji MJ, Markert E, MacKay GM, Kamphorst JJ, Graham D, Faulds K, Fazli L, Gleave ME, Avezov E, Edwards J, Yin H, Sumpton D, Blyth K, Close P, Murphy DJ, Zanivan S, Leung HY. THEM6-mediated reprogramming of lipid metabolism supports treatment resistance in prostate cancer. EMBO Molecular Medicine. 2022;14:e14764
Camargo L, Samji S, Lilla S, Zanivan S, Bulleid N, Hartley R, Delles C, Leiper J, Fuller W, Montezano A, Touyz R. Proteomic profile of cysteine oxidation in vacsular smooth muscle cells in human hypertension. J Hypertens. 2022;40:e225-e226.
Gioelli N, Neilson LJ, Wei N, Villari G, Chen W, Kuhle B, Ehling M, Maione F, Willox S, Brundu S, Avanzato D, Koulouras G, Mazzone M, Giraudo E, Yang XL, Valdembri D, Zanivan S, Serini G. Neuropilin 1 and its inhibitory ligand mini-tryptophanyl-tRNA synthetase inversely regulate VE-cadherin turnover and vascular permeability. Nat Commun. 2022;13:4188.
Kay EJ, Paterson K, Riero-Domingo C, Sumpton D, Däbritz JHM, Tardito S, Boldrini C, Hernandez-Fernaud JR, Athineos D, Dhayade S, Stepanova E, Gjerga E, Neilson LJ, Lilla S, Hedley A, Koulouras G, McGregor G, Jamieson C, Johson RM, Park M, Kirschner K, Miller C, Kamphorst JJ, Loayza-Puch F, Saez-Rodriguez J, Mazzone M, Blyth K, Zagoni M, Zanivan S. Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix. Nature Metabolism. 2022;4(6):693-710.
McGarry DJ, Castino G, Lilla S, Carnet A, Kelly L, Micovic K, Zanivan S, Olson MF. MICAL1 activation by PAK1 mediates actin filament disassembly. Cell Reports. 2022;41:111442
Närvä E, Taskinen ME, Lilla S, Isomursu A, Pietilä M, Weltner J, Isola J, Sihto H, Joensuu H, Zanivan S, Norman J, Ivaska J. MASTL is enriched in cancerous and pluripotent stem cells and influences OCT1/OCT4 levels. iScience. 2022;25:104459.
Nikolatou K, Sandilands E, Roman-Fernandez A, Cumming EM, Freckmann EC, Lilla S, Buetow L, McGarry L, Neilson M, Shaw R, Strachan D, Miller C, Huang DT, McNeish IA, Norman JC, Zanivan S, Bryant D. PTEN deficiency exposes a requirement for an ARF GTPase module in integrin-dependent invasion in ovarian cancer. bioRxiv. 2022;Volume:2022.2011.2029.518198.
Salji MJ, Blomme A, Däbritz JHM, Repiscak P, Lilla S, Patel R, Sumpton D, van den Broek NJF, Daly R, Zanivan S, Leung HY. Multi-omics & pathway analysis identify potential roles for tumor N-acetyl aspartate accumulation in murine models of castration-resistant prostate cancer. iScience. 2022;25:104056.
Schmidt T, Dabrowska A, Waldron JA, Hodge K, Koulouras G, Gabrielsen M, Munro J, Tack DC, Harris G, McGhee E, Scott D, Carlin LM, Huang D, Le Quesne J, Zanivan S, Wilczynska A, Bushell M. Purine-rich RNA sequences in the 5’UTR site-specifically regulate eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation. bioRxiv. 2022;Volume:2022.2008.2008.503179.
Kay EJ, Zanivan S. Methylmalonic acid: an age-related metabolite that drives tumour aggressiveness. Nat Metab. 2022; 4:412–413
Kugeratski FG, Santi A, Zanivan S. Extracellular vesicles as central regulators of blood vessel function in cancer. Science Signaling. 2022;15(753):eaaz4742.
2021
Ahmed SF, Buetow L, Gabrielsen M, Lilla S, Sibbet GJ, Sumpton D, Zanivan S, Hedley A, Clark W, Huang DT. E3 ligase-inactivation rewires CBL interactome to elicit oncogenesis by hijacking RTK-CBL-CIN85 axis. Oncogene. 2021;40(12):2149-2164.
Budden T, Gaudy-Marqueste C, Porter A, Kay E, Gurung S, Earnshaw CH, Roeck K, Craig S, Traves V, Krutmann J, Muller P, Motta L, Zanivan S, Malliri A, Furney SJ, Nagore E, Virós A. Ultraviolet light-induced collagen degradation inhibits melanoma invasion. Nat Commun. 2021;12:2742.
Gillen SL, Giacomelli C, Hodge K, Zanivan S, Bushell M, Wilczynska A. Differential regulation of mRNA fate by the human Ccr4-Not complex is driven by coding sequence composition and mRNA localization. Genome Biol. 2021;22:284.
Kugeratski FG, Hodge K, Lilla S, McAndrews KM, Zhou X, Hwang RF, Zanivan S, Kalluri R. Quantitative proteomics identifies the core proteome of exosomes with syntenin-1 as the highest abundant protein and a putative universal biomarker. Nat Cell Biol. 2021;23(6):631-641.
Mackey JBG, McFarlane AJ, Jamieson T, Jackstadt R, Raffo-Iraolagoitia XL, Secklehner J, Cortes-Lavaud X, Fercoq F, Clarke W, Hedley A, Gilroy K, Lilla S, Vuononvirta J, Graham GJ, De Filippo K, Murphy DJ, Steele CW, Norman JC, Bird TG, Mann DA, Morton JP, Zanivan S, Sansom OJ, Carlin LM. Maturation, developmental site, and pathology dictate murine neutrophil function. bioRxiv. 2021.
Marco S, Neilson M, Moore M, Perez-Garcia A, Hall H, Mitchell L, Lilla S, Blanco GR, Hedley A, Zanivan S, Norman JC. Nuclear-capture of endosomes depletes nuclear G-actin to promote SRF/MRTF activation and cancer cell invasion. Nat Commun. 2021 Nov 24;12(1):6829.
Martinez RS, Salji MJ, Rushworth L, Ntala C, Rodriguez Blanco G, Hedley A, Clark W, Peixoto P, Hervouet E, Renaude E, Kung SHY, Galbraith LCA, Nixon C, Lilla S, Mackay GM, Fazli L, Gaughan L, Sumpton D, Gleave ME, Zanivan S, Blomme A, Leung HY. SLFN5 regulates LAT1-mediated mTOR activation in castration-resistant prostate cancer. Cancer Res. 2021;81: 3664–78
Nacke M, Sandilands E, Nikolatou K, Román-Fernández Á, Mason S, Patel R, Lilla S, Yelland T, Galbraith LCA, Freckmann EC, McGarry L, Morton JP, Shanks E, Leung HY, Markert E, Ismail S, Zanivan S, Blyth K, Bryant DM. An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism. Nat Commun. 2021;12:1623.
Phatak V, von Grabowiecki Y, Janus J, Officer L, Behan C, Aschauer L, Pinon L, Mackay H, Zanivan S, Norman JC, Kelly M, Le Quesne J, Muller PAJ. Mutant p53 promotes RCP-dependent chemoresistance coinciding with increased delivery of P-glycoprotein to the plasma membrane. Cell Death Dis. 2021;12(2):207.
Domen A, Quatannens D, Zanivan S, Deben C, Van Audenaerde J, Smits E, Wouters A, Lardon F, Roeyen G, Verhoeven Y, Janssens A, Vandamme T, van Dam P, Peeters M, Prenen H. Cancer-Associated Fibroblasts as a Common Orchestrator of Therapy Resistance in Lung and Pancreatic Cancer. Cancers (Basel). 2021;13:987
Kay EJ, Koulouras G, Zanivan S. Regulation of Extracellular Matrix Production in Activated Fibroblasts: Roles of Amino Acid Metabolism in Collagen Synthesis. Front Oncol. 2021;11:719922.
Kay EJ, Zanivan S. Metabolic pathways fuelling protumourigenic cancer-associated fibroblast functions. Current Opinion in Systems Biology. 2021;28:100377.
Kay EJ, Zanivan S. Two opposing sub-populations of fibroblasts decide progression of pancreatic cancer. Cancer Cell. 2021; 39:1175-1177.
Paterson K, Zanivan S, Glasspool R, Coffelt SB, Zagnoni M. Microfluidic technologies for immunotherapy studies on solid tumours. Lab Chip. 2021;21:2306-2329.
2020
Ahmed SF, Buetow L, Gabrielsen M, Lilla S, Chatrin C, Sibbet GJ, Zanivan S, Huang DT. DELTEX2 C-terminal domain recognizes and recruits ADP-ribosylated proteins for ubiquitination. Science Advances. 2020;6(34):eabc0629.
Blomme A, Ford CA, Mui E, Patel R, Ntala C, Jamieson LE, Planque M, McGregor GH, Peixoto P, Hervouet E, Nixon C, Salji M, Gaughan L, Markert E, Repiscak P, Sumpton D, Rodriguez Blanco G, Lilla S, Kamphorst JJ, Graham D, Faulds K, MacKay GM, Fendt S-M, Zanivan S, Leung HY. 2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer. Nat Commun. 2020; 11: 2508
Cao X, Lilla S, Cao Z, Pringle MA, Oka OBV, Robinson PJ, Szmaja T, van Lith M, Zanivan S, Bulleid NJ. The mammalian cytosolic thioredoxin reductase pathway acts via a membrane protein to reduce ER-localised proteins. Journal of cell science. 2020;
Lobo MJ, Reverte-Salisa L, Chao YC, Koschinski A, Gesellchen F, Subramaniam G, Jiang H, Pace S, Larcom N, Paolocci E, Pfeifer A, Zanivan S, Zaccolo M. Phosphodiesterase 2A2 regulates mitochondria clearance through Parkin-dependent mitophagy. Commun Biol. 2020;3(1):596.
Loveridge CJ, Slater S, Campbell KJ, Nam NA, Knight J, Ahmad I, Hedley A, Lilla S, Repiscak P, Patel R, Salji M, Fleming J, Mitchell L, Nixon C, Strathdee D, Neilson M, Ntala C, Bryson S, Zanivan S, Edwards J, Robson CN, Goodyear CS, Blyth K, Leung HY. BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration. Oncogene. 2020; 39: 1797–1806
Oizel K, Tait-Mulder J, Fernandez-de-Cossio-Diaz J, Pietzke M, Brunton H, Lilla S, Dhayade S, Athineos D, Blanco GR, Sumpton D, Mackay GM, Blyth K, Zanivan SR, Meiser J, Vazquez A. Formate induces a metabolic switch in nucleotide and energy metabolism. Cell death & disease. 2020;11:310.
Tait-Mulder J, Hodge K, Sumpton D, Zanivan S, Vazquez A. The conversion of formate into purines stimulates mTORC1 leading to CAD-dependent activation of pyrimidine synthesis. Cancer & Metabolism. 2020;8(1):20.
Taskinen ME, Närvä E, Conway JRW, Hinojosa LS, Lilla S, Mai A, De Franceschi N, Elo LL, Grosse R, Zanivan S, Norman JC, Ivaska J. MASTL promotes cell contractility and motility through kinase-independent signaling. J Cell Biol. 2020;219:e201906204
Unbekandt M, Lilla S, Zanivan S, Olson MF. The CDC42 effector protein MRCKβ autophosphorylates on Threonine 1108. Small GTPases. 2020;11(6):451-460.
2019
Ferraro DA, Patella F, Zanivan S, Donato C, Aceto N, Giannotta M, Dejana E, Diepenbruck M, Christofori G, Buess M. Endothelial cell-derived nidogen-1 inhibits migration of SK-BR-3 breast cancer cells. BMC Cancer. 2019; 19: 312.
Kugeratski FG, Atkinson SJ, Neilson LJ, Lilla S, Knight JRP, Serneels J, Juin A, Ismail S, Bryant DM, Markert EK, Machesky LM, Mazzone M, Sansom OJ, Zanivan S. Hypoxic cancer-associated fibroblasts increase NCBP2-AS2/HIAR to promote endothelial sprouting through enhanced VEGF signaling. Science signaling 2019; 12: eaan8247.
Whitelaw JA, Lilla S, Paul NR, Fort L, Zanivan S, Machesky LM. CYRI/ Fam49 Proteins Represent a New Class of Rac1 Interactors. Communicative & integrative biology. 2019;12:112-118.
Wilczynska A, Gillen SL, Schmidt T, Meijer HA, Jukes-Jones R, Langlais C, Kopra K, Lu WT, Godfrey JD, Hawley BR, Hodge K, Zanivan S, Cain K, Le Quesne J, Bushell M. eIF4A2 drives repression of translation at initiation by Ccr4-Not through purine-rich motifs in the 5'UTR. Genome Biol. 2019; 20: 262.
2018
Dandoulaki M, Petsalaki E, Sumpton D, Zanivan S, Zachos G. Src activation by Chk1 promotes actin patch formation and prevents chromatin bridge breakage in cytokinesis. J Cell Biol 2018; 217: 3071–3089
Fort L, Batista JM, Thomason PA, Spence HJ, Whitelaw JA, Tweedy L, Greaves J, Martin KJ, Anderson KI, Brown P, Lilla S, Neilson MP, Tafelmeyer P, Zanivan S, Ismail S, Bryant DM, Tomkinson NCO, Chamberlain LH, Mastick GS, Insall RH, Machesky LM. Fam49/CYRI interacts with Rac1 and locally suppresses protrusions. Nat Cell Biol. 2018 ; 20: 1159-71.
Kugeratski FG, Batista M, Lima CVP, Neilson LJ, da Cunha ES, de Godoy LM, Zanivan S, Krieger MA, Marchini FK. Mitogen-Activated Protein Kinase Kinase 5 Regulates Proliferation and Biosynthetic Processes in Procyclic Forms of Trypanosoma brucei. J Proteome Res 2018; 17: 108-18.
Novo D, Heath N, Mitchell L, Caligiuri G, MacFarlane A, Reijmer D, Charlton L, Knight J, Calka M, McGhee E, Dornier E, Sumpton D, Mason S, Echard A, Klinkert K, et al. Mutant p53s generate pro-invasive niches by influencing exosome podocalyxin levels. Nat Commun 2018; 9: 5069.
Port J, Muthalagu N, Raja M, Ceteci F, Monteverde T, Kruspig B, Hedley A, Kalna G, Lilla S, Neilson L, Brucoli M, Gyuraszova K, Tait-Mulder J, Mezna M, Svambaryte S, et al. Colorectal Tumors Require NUAK1 for Protection from Oxidative Stress. Cancer Discov 2018;8(5):632-47
van der Reest J, Lilla S, Zheng L, Zanivan S, Gottlieb E. Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress. Nat Commun 2018; 9: 1581.
Santi A, Kugeratski FG, Zanivan S. Cancer Associated Fibroblasts: The Architects of Stroma Remodeling. Proteomics 2018; 18: e1700167.
2017
Diaz-Vera J, Palmer S, Hernandez-Fernaud JR, Dornier E, Mitchell LE, Macpherson I, Edwards J, Zanivan S, Norman JC. A proteomic approach to identify endosomal cargoes controlling cancer invasiveness. J Cell Sci 2017; 130: 697-711
Hernandez-Fernaud JR, Ruengeler E, Casazza A, Neilson LJ, Pulleine E, Santi A, Ismail S, Lilla S, Dhayade S, MacPherson IR, McNeish I, Ennis D, Ali H, Kugeratski FG, Al Khamici H, van den Biggelaar M, van den Berghe PV, Cloix C, McDonald L, Millan D et al. Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity. Nat Commun 2017; 8: 14206
Reid SE, Kay EJ, Neilson LJ, Henze AT, Serneels J, McGhee EJ, Dhayade S, Nixon C, Mackey JB, Santi A, Swaminathan K, Athineos D, Papalazarou V, Patella F, Roman-Fernandez A, ElMaghloob Y, Hernandez-Fernaud JR, Adams RH, Ismail S, Bryant DM et al. Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium. EMBO 2017; 36: 2373-89
van den Eshof BL, Hoogendijk AJ, Simpson PJ, van Alphen FPJ, Zanivan S, Mertens K, Meijer AB, van den Biggelaar M. Paradigm of Biased PAR1 (Protease-Activated Receptor-1) Activation and Inhibition in Endothelial Cells Dissected by Phosphoproteomics. Arterioscler Thromb Vasc Biol 2017; 37: 1891-1902
Norman J, Zanivan S (2017) Chloride intracellular channel 3: A secreted pro-invasive oxidoreductase. Cell Cycle: 16; 1993-4
Reid SE, Zanivan S. Tumor stiffness extends its grip on the metastatic microenvironment. Mol Cell Oncol 2017; 4: e1372866
2016
Patella F, Neilson LJ, Athineos D, Erami Z, Anderson KI, Blyth K, Ryan KM, Zanivan S. In-Depth Proteomics Identifies a Role for Autophagy in Controlling Reactive Oxygen Species Mediated Endothelial Permeability. J Proteome Res. 2016; 15: 2187-97
Clarke CJ, Berg TJ, Birch J, Ennis D, Mitchell L, Cloix C, Campbell A, Sumpton D, Nixon C, Campbell K, Bridgeman VL, Vermeulen PB, Foo S, Kostaras E, Jones JL, Haywood L, Pulleine E, Yin HB, Strathdee D, Sansom O, Blyth K, McNeish I, Zanivan S, Reynolds AR, Norman JC. The Initiator Methionine tRNA Drives Secretion of Type II Collagen from Stromal Fibroblasts to Promote Tumor Growth and Angiogenesis. Curr Biol. 2016; 26: 755-65
Lab Members
Postdoctoral Scientists
Paula Duch Gili
Emily Kay
Britt Sterken
Ashton Theakstone
Scientific Officers
Maja Bailey
Lisa Neilson
Clinical Research Fellow
Douglas Cartwright
PhD Student
Kunal Reshamwala
Former Lab Members
Fernanda Kugeratski (Post-doc, MD Anderson, USA)
Francesca Patella (Post-doc, University College London, UK)
Juan Ramon Hernandez (Manager Proteomic Facility, University of Warwick, UK)
Steven Reid (Post-doc, Lund University, SE)
Maartje van den Biggelaar (Scientist, Sanquin Research, Amsterdam, NL)
