Prof Owen Sansom FRSE, FMEDSci - Colorectal Cancer and Wnt Signalling

Introduction

SansomO

Colorectal cancer (CRC)—the third most common cancer in the UK and the second leading cause of cancer mortality—is a heterogeneous disease comprising distinct molecular subgroups that differ in their histopathological features, prognosis, and response to therapy. Despite advances in the detection and treatment of early-stage disease, patients with advanced, recurrent, or metastatic CRCs have few therapeutic options and a dismal prognosis. Utilising state-of-the-art preclinical models harbouring key driver mutations, our group is interrogating the molecular mechanisms underpinning CRC initiation, progression, response to therapy, and metastasis. Our overarching goals are to identify early-stage diagnostic biomarkers and develop stage- and subtype-specific targeted therapies.
As part of these efforts, we are major contributors to a number of large cancer consortia, with the aim of driving more effective therapeutic approaches in colorectal cancer. Our group leads a Europe-wide, CRUK-funded consortium of basic, translational, and clinical scientists (ACRCelerate—Colorectal Cancer Stratified Medicine Network) to identify new therapeutic targets for the different CRC subtypes and deliver molecular insights with the potential to inform clinical decision-making and patient stratification. Similarly, through participation in the CRUK Grand Challenge Rosetta consortium, we are working to therapeutically exploit the altered metabolic dependencies of oncogene-addicted CRCs, and determine how distinct tumour metabolic profiles can confer resistance or predict sensitivity to standard-of-care or novel targeted therapies. Moreover, as a key contributor to the CRUK Grand Challenge SpecifiCancer consortium, we are employing transcriptional, epigenetic, and proteomic approaches to understand why there are tissue- and cell type-specific differences in the response to oncogenic mutations, with the aim of developing methods to suppress the impact of these mutations in cancer.
In addition, we are partnering with a number of leading industry innovator to accelerate the path from bench to bedside. For example, in partnership with Novartis, we are working towards the development of novel KRAS inhibitors, to address a pressing clinical need in colorectal cancer.

Want to find out more about Professor Sansom's work?

Read about his 2009 Nature paper on the CRUK science blog and listen to him talking about bowel cancer stem cells.

See a Google Hangout on the subject of red meat and cancer featuring Owen Sansom and Kathryn Bradbury from the University of Oxford: https://www.youtube.com/watch?v=jS1QW74wJRw​

Lab Report

Key Publications

Jackstadt R, van Hooff SR, Leach JD, Cortes-Lavaud X, Lohuis JO, Ridgway RA, Wouters VM, Roper J, Kendall TJ, Roxburgh CS, Horgan PG, Nixon C, Nourse C, Gunzer M, Clark W, Hedley A, Yilmaz OH, Rashid M, Bailey P, Biankin AV, Campbell AD, Adams DJ, Barry ST, Steele CW, Medema JP, Sansom OJ. Epithelial NOTCH Signaling Rewires the Tumor Microenvironment of Colorectal Cancer to Drive Poor-Prognosis Subtypes and Metastasis. Cancer cell. 2019; 36: 319-336.e317.

Johansson J, Naszai M, Hodder MC, Pickering KA, Miller BW, Ridgway RA, Yu Y, Peschard P, Brachmann S, Campbell AD, Cordero JB, Sansom OJ. RAL GTPases Drive Intestinal Stem Cell Function and Regeneration through Internalization of WNT Signalosomes. Cell Stem Cell. 2019; 24: 592-607.e7.

Faller WJ, Jackson TJ, Knight JR, Ridgway RA, Jamieson T, Karim SA, Jones C, Radulescu S, Huels DJ, Myant KB, Dudek KM, Casey HA, Scopelliti A, Cordero JB, Vidal M, Pende M, Ryazanov AG, Sonenberg N, Meyuhas O, Hall MN, Bushell M, Willis AE, Sansom OJ. mTORC1-mediated translational elongation limits intestinal tumour initiation and growth. Nature. 2014; 517: 497–500

Myant KB, Cammareri P, McGhee EJ, Ridgway RA, Huels DJ, Cordero JB, Schwitalla S, Kalna G, Ogg EL, Athineos D, Timpson P, Vidal M, Murray GI, Greten FR, Anderson KI, Sansom OJ. ROS production and NF-κB activation triggered by RAC1 facilitate WNT-driven intestinal stem cell proliferation and colorectal cancer initiation. Cell Stem Cell. 2013; 12: 761-73

Ashton GH, Morton JP, Myant K, Phesse TJ, Ridgway RA, Marsh V, Wilkins JA, Athineos D, Muncan V, Kemp R, Neufeld K, Clevers H, Brunton V, Winton DJ, Wang X, Sears RC, Clarke AR, Frame MC, Sansom OJ. Focal adhesion kinase is required for intestinal regeneration and tumorigenesis downstream of Wnt/c-Myc signaling. Dev Cell. 2010; 19: 259-69

Morton JP, Timpson P, Karim SA, Ridgway RA, Athineos D, Doyle B, Jamieson NB, Oien KA, Lowy AM, Brunton VG, Frame MC, Evans TR, Sansom OJ. Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer. Proc Natl Acad Sci USA. 2010; 107: 246-51

Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, Danenberg E, Clarke AR, Sansom OJ, Clevers H. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature. 2009 457: 608-11

Sansom OJ, Meniel VS, Muncan V, Phesse TJ, Wilkins JA, Reed KR, Vass JK, Athineos DA, Clevers H, Clarke AR. c-Myc deletion rescues Apc deficiency in the small intestine. Nature. 2007; 446: 676-9

Sansom OJ, Reed KR, Hayes AJ, Ireland H, Brinkmann H, Newton IP, Batlle E, Simon-Assmann P, Clevers H, Nathke IS, Clarke AR, Winton DJ. Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration. Genes Dev. 2004; 18: 1385-90

Biography

Education and qualifications

2002: PhD, University of Edinburgh, Supervisors Alan Clarke and Andrew Wylie
1997: MRes, Biology, University of Manchester
1996: BSc, Genetics (First Class Honours), University of Nottingham

Appointments

2017-present: Director, CRUK Beatson Institute, Glasgow
2011-2017 Deputy Director, CRUK Beatson Institute, Glasgow
2005-present: Group Leader, CRUK Beatson Institute, Glasgow
2000-2005: Postdoctoral Fellow with Alan Clarke, University of Cardiff

Current committee membership

NC3Rs Student Panel
CRUK Programme Grants interviewer
CRUK Drug Discovery Panel
North West Cancer Research Panel
CRUK Pancreatic Cancer Strategy Panel
Advisory Board, MRC Toxicology Unit, Leicester
Advisory Board, Center for Personalized Cancer Therapeutics, Mount Sinai
Advisory Board, Centre of Excellence in Translational Cancer Biology, Academy of Finland
Editorial Board, Disease Models and Mechanisms
Organising Committee, NCRI Cancer Conference, Liverpool

Honours and awards

Fellow of the Academy of Medical Sciences, 2017
CRUK Future Leaders in Cancer Research Prize, 2012
Fellow of the Royal Society of Edinburgh, 2012
BACR/AstraZeneca Young Scientist Frank Rose Award, 2007

Recent Publications

2021

Ahmaderaghi B, Amirkhah R, Jackson J, Lannagan TR, Gilroy K, Malla SB, Redmond KL, Consortium A, Maughan T, Leedham S, Campbell AS, Sansom OJ, Lawler M, Dunne PD. The Molecular Subtyping Resource (MouSR): a user-friendly tool for rapid biological discovery from human or mouse transcriptional data. bioRxiv. 2021;

Alexander PG, Roseweir AK, Pennel KAF, van Wyk HC, Powell A, McMillan DC, Horgan PG, Kelly C, Hay J, Sansom O, Harkin A, Roxburgh CSD, Graham J, Church DN, Tomlinson I, Saunders M, Iveson TJ, Edwards J, Park JH. The Glasgow Microenvironment Score associates with prognosis and adjuvant chemotherapy response in colorectal cancer. Br J Cancer. 2021;124:786-796. 

Dreyer SB, Upstill-Goddard R, Paulus-Hock V, Paris C, Lampraki EM, Dray E, Serrels B, Caligiuri G, Rebus S, Plenker D, Galluzzo Z, Brunton H, Cunningham R, Tesson M, Nourse C, Bailey UM, Jones M, Moran-Jones K, Wright DW, Duthie F, Oien K, Evers L, McKay CJ, McGregor GA, Gulati A, Brough R, Bajrami I, Pettitt S, Dziubinski ML, Candido J, Balkwill F, Barry ST, Grützmann R, Rahib L, Johns A, Pajic M, Froeling FEM, Beer P, Musgrove EA, Petersen GM, Ashworth A, Frame MC, Crawford HC, Simeone DM, Lord C, Mukhopadhyay D, Pilarsky C, Tuveson DA, Cooke SL, Jamieson NB, Morton JP, Sansom OJ, Bailey PJ, Biankin AV, Chang DK. Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer. Gastroenterology. 2021;160(1):362-377.e313.

Dunbar K, Valanciute A, Lima ACS, Vinuela PF, Jamieson T, Rajasekaran V, Blackmur J, Ochocka-Fox AM, Guazzelli A, Cammareri P, Arends MJ, Sansom OJ, Myant KB, Farrington SM, Dunlop MG, Din FVN. Aspirin Rescues Wnt-Driven Stem-like Phenotype in Human Intestinal Organoids and Increases the Wnt Antagonist Dickkopf-1. Cell Mol Gastroenterol Hepatol. 2021;11(2):465-489.

Falcomata C, Barthel S, Ulrich A, Diersch S, Veltkamp C, Rad L, Boniolo F, Solar M, Steiger K, Seidler B, Zukowska M, Madej J, Wang M, Ollinger R, Maresch R, Barenboim M, Eser S, Tschurtschenthaler M, Mehrabi A, Roessler S, Goeppert B, Kind A, Schnieke A, Robles MS, Bradley A, Schmid RM, Schmidt-Supprian M, Reichert M, Weichert W, Sansom OJ, Morton JP, Rad R, Schneider G, Saur D. Genetic screens identify a context-specific PI3K/p27Kip1 node driving extrahepatic biliary cancer. Cancer Discov. 2021.

Flanagan DJ, Pentinmikko N, Luopajärvi K, Willis NJ, Gilroy K, Raven AP, McGarry L, Englund JI, Webb AT, Scharaw S, Nasreddin N, Hodder MC, Ridgway RA, Minnee E, Sphyris N, Gilchrist E, Najumudeen AK, Romagnolo B, Perret C, Williams AC, Clevers H, Nummela P, Lähde M, Alitalo K, Hietakangas V, Hedley A, Clark W, Nixon C, Kirschner K, Jones EY, Ristimäki A, Leedham SJ, Fish PV, Vincent JP, Katajisto P, Sansom OJ. NOTUM from Apc-mutant cells biases clonal competition to initiate cancer. Nature. 2021;594(7863):430-435.

Floerchinger A, Murphy KJ, Latham SL, Warren SC, McCulloch AT, Lee YK, Stoehr J, Mélénec P, Guaman CS, Metcalf XL, Lee V, Zaratzian A, Da Silva A, Tayao M, Rolo S, Phimmachanh M, Sultani G, McDonald L, Mason SM, Ferrari N, Ooms LM, Johnsson AE, Spence HJ, Olson MF, Machesky LM, Sansom OJ, Morton JP, Mitchell CA, Samuel MS, Croucher DR, Welch HCE, Blyth K, Caldon CE, Herrmann D, Anderson KI, Timpson P, Nobis M. Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: Guidance using optical window intravital FRET imaging. Cell Rep. 2021;36(11):109689.

Galbraith LCA, Mui E, Nixon C, Hedley A, Strachan D, MacKay G, Sumpton D, Sansom OJ, Leung HY, Ahmad I. PPAR-gamma induced AKT3 expression increases levels of mitochondrial biogenesis driving prostate cancer. Oncogene. 2021;40:2355-2366.

Grosso S, Marini A, Gyuraszova K, Voorde JV, Sfakianos A, Garland GD, Tenor AR, Mordue R, Chernova T, Morone N, Sereno M, Smith CP, Officer L, Farahmand P, Rooney C, Sumpton D, Das M, Teodósio A, Ficken C, Martin MG, Spriggs RV, Sun XM, Bushell M, Sansom OJ, Murphy D, MacFarlane M, Le Quesne JPC, Willis AE. The pathogenesis of mesothelioma is driven by a dysregulated translatome. Nat Commun. 2021;12:4920.

Gudiño V, Pohl S, Billard CV, Cammareri P, Bolado A, Aitken S, Stevenson D, Hall AE, Agostino M, Cassidy J, Nixon C, von Kriegsheim A, Freile P, Popplewell L, Dickson G, Murphy L, Wheeler A, Dunlop M, Din F, Strathdee D, Sansom OJ, Myant KB. RAC1B modulates intestinal tumourigenesis via modulation of WNT and EGFR signalling pathways. Nat Commun. 2021;12:2335.

Guillermin O, Angelis N, Sidor CM, Ridgway R, Baulies A, Kucharska A, Antas P, Rose MR, Cordero J, Sansom O, Li VSW, Thompson BJ. Wnt and Src signals converge on YAP-TEAD to drive intestinal regeneration. Embo j. 2021:e105770. 

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. 

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.

Knight JRP, Alexandrou C, Skalka GL, Vlahov N, Pennel K, Officer L, Teodosio A, Kanellos G, Gay DM, May-Wilson S, Smith EM, Najumudeen AK, Gilroy K, Ridgway RA, Flanagan DJ, Smith RCL, McDonald L, MacKay C, Cheasty A, McArthur K, Stanway E, Leach JD, Jackstadt R, Waldron JA, Campbell AD, Vlachogiannis G, Valeri N, Haigis KM, Sonenberg N, Proud CG, Jones NP, Swarbrick ME, McKinnon HJ, Faller WJ, Le Quesne J, Edwards J, Willis AE, Bushell M, Sansom OJ. MNK Inhibition Sensitizes KRAS-Mutant Colorectal Cancer to mTORC1 Inhibition by Reducing eIF4E Phosphorylation and c-MYC Expression. Cancer Discov. 2021;11(5):1228-1247.

Krotenberg Garcia A, Fumagalli A, Le HQ, Jackstadt R, Lannagan TRM, Sansom OJ, van Rheenen J, Suijkerbuijk SJE. Active elimination of intestinal cells drives oncogenic growth in organoids. Cell Rep. 2021;36:109307. 

Lähde M, Heino S, Högström J, Kaijalainen S, Anisimov A, Flanagan D, Kallio P, Leppänen VM, Ristimäki A, Ritvos O, Wu K, Tammela T, Hodder M, Sansom OJ, Alitalo K. Expression of R-Spondin 1 in Apc(Min/+) Mice Suppresses Growth of Intestinal Adenomas by Altering Wnt and Transforming Growth Factor Beta Signaling. Gastroenterology. 2021;160(1):245-259.

Lampis A, Hahne JC, Gasparini P, Cascione L, Hedayat S, Vlachogiannis G, Murgia C, Fontana E, Edwards J, Horgan PG, Terracciano L, Sansom OJ, Martins CD, Kramer-Marek G, Croce CM, Braconi C, Fassan M, Valeri N. MIR21-induced loss of junctional adhesion molecule A promotes activation of oncogenic pathways, progression and metastasis in colorectal cancer. Cell Death Differ. 2021.

Leach JDG, Vlahov N, Tsantoulis P, Ridgway RA, Flanagan DJ, Gilroy K, Sphyris N, Vázquez EG, Vincent DF, Faller WJ, Hodder MC, Raven A, Fey S, Najumudeen AK, Strathdee D, Nixon C, Hughes M, Clark W, Shaw R, van Hooff SR, Huels DJ, Medema JP, Barry ST, Frame MC, Unciti-Broceta A, Leedham SJ, Inman GJ, Jackstadt R, Thompson BJ, Campbell AD, Tejpar S, Sansom OJ. Oncogenic BRAF, unrestrained by TGFβ-receptor signalling, drives right-sided colonic tumorigenesis. Nat Commun. 2021;12:3464.

Mackey JBG, McFarlane AJ, Jamieson T, Jackstadt R, Raffo-Iraolagoitia XL, Secklehner J, Cortes-Lavaud X, Fercoq F, Clarke W, Hedley A, Gilroy K, Lilla S, Vuononvirta J, Graham GJ, De Filippo K, Murphy DJ, Steele CW, Norman JC, Bird TG, Mann DA, Morton JP, Zanivan S, Sansom OJ, Carlin LM. Maturation, developmental site, and pathology dictate murine neutrophil function. bioRxiv. 2021.

Minnis-Lyons SE, Ferreira-González S, Aleksieva N, Man TY, Gadd VL, Williams MJ, Guest RV, Lu WY, Dwyer BJ, Jamieson T, Nixon C, Van Hul N, Lemaigre FP, McCafferty J, Leclercq IA, Sansom OJ, Boulter L, Forbes SJ. Notch-IGF1 signaling during liver regeneration drives biliary epithelial cell expansion and inhibits hepatocyte differentiation. Sci Signal. 2021;14(688).

Murta T, Steven RT, Nikula CJ, Thomas SA, Zeiger LB, Dexter A, Elia EA, Yan B, Campbell AD, Goodwin RJA, Takáts Z, Sansom OJ, Bunch J. Implications of Peak Selection in the Interpretation of Unsupervised Mass Spectrometry Imaging Data Analyses. Anal Chem. 2021;

Najumudeen AK, Ceteci F, Fey SK, Hamm G, Steven RT, Hall H, Nikula CJ, Dexter A, Murta T, Race AM, Sumpton D, Vlahov N, Gay DM, Knight JRP, Jackstadt R, Leach JDG, Ridgway RA, Johnson ER, Nixon C, Hedley A, et al. The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer. Nat Genet. 2021;53:16-26.

Nászai M, Bellec K, Yu Y, Román-Fernández A, Sandilands E, Johansson J, Campbell AD, Norman JC, Sansom OJ, Bryant DM, Cordero JB. RAL GTPases mediate EGFR-driven intestinal stem cell proliferation and tumourigenesis. Elife. 2021;10.

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.

Pickering KA, Gilroy K, Cassidy JW, Fey SK, Najumudeen AK, Zeiger LB, Vincent DF, Gay DM, Johansson J, Fordham RP, Miller B, Clark W, Hedley A, Unal EB, Kiel C, McGhee E, Machesky LM, Nixon C, Johnsson AE, Bain M, et al. A RAC-GEF network critical for early intestinal tumourigenesis. Nat Commun. 2021;12:56.

Race AM, Sutton D, Hamm G, Maglennon G, Morton JP, Strittmatter N, Campbell A, Sansom OJ, Wang Y, Barry ST, Takáts Z, Goodwin RJA, Bunch J. Deep Learning-Based Annotation Transfer between Molecular Imaging Modalities: An Automated Workflow for Multimodal Data Integration. Anal Chem. 2021;93(6):3061-3071.

Ramesh P, Lannagan TRM, Jackstadt R, Atencia Taboada L, Lansu N, Wirapati P, van Hooff SR, Dekker D, Pritchard J, Kirov AB, van Neerven SM, Tejpar S, Kops G, Sansom OJ, Medema JP. BCL-XL is crucial for progression through the adenoma-to-carcinoma sequence of colorectal cancer. Cell Death Differ. 2021.

Sacchetti A, Teeuwssen M, Verhagen M, Joosten R, Xu T, Stabile R, van der Steen B, Watson MM, Gusinac A, Kim WK, Ubink I, Van de Werken HJ, Fumagalli A, Paauwe M, Van Rheenen J, Sansom OJ, Kranenburg O, Fodde R. Phenotypic plasticity underlies local invasion and distant metastasis in colon cancer. Elife. 2021;10. 

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.

Swaminathan K, Campbell A, Papalazarou V, Jaber-Hijazi F, Nixon C, McGhee E, Strathdee D, Sansom OJ, Machesky LM. The RAC1 Target NCKAP1 Plays a Crucial Role in the Progression of Braf;Pten-Driven Melanoma in Mice. J Invest Dermatol. 2021;141(3):628-637.e615.

Tajan M, Hennequart M, Cheung EC, Zani F, Hock AK, Legrave N, Maddocks ODK, Ridgway RA, Athineos D, Suárez-Bonnet A, Ludwig RL, Novellasdemunt L, Angelis N, Li VSW, Vlachogiannis G, Valeri N, Mainolfi N, Suri V, Friedman A, Manfredi M, et al. Serine synthesis pathway inhibition cooperates with dietary serine and glycine limitation for cancer therapy. Nat Commun. 2021;12:366.

van der Weyden L, Harle V, Turner G, Offord V, Iyer V, Droop A, Swiatkowska A, Rabbie R, Campbell AD, Sansom OJ, Pardo M, Choudhary JS, Ferreira I, Tullett M, Arends MJ, Speak AO, Adams DJ. CRISPR activation screen in mice identifies novel membrane proteins enhancing pulmonary metastatic colonisation. Commun Biol. 2021;4(1):395.

Gillespie MA, Steele CW, Lannagan TRM, Sansom OJ, Roxburgh CSD. Pre-clinical modelling of rectal cancer to develop novel radiotherapy-based treatment strategies. Oncol Rev. 2021;15:511.

Knight JRP, Sansom OJ. Tuning protein synthesis for cancer therapy. Mol Cell Oncol. 2021;8:1884034.

Lannagan TR, Jackstadt R, Leedham SJ, Sansom OJ. Advances in colon cancer research: in vitro and animal models. Curr Opin Genet Dev. 2021;66:50-56.

Rosenfeldt MT, O'Prey J, Lindsay CR, Nixon C, Roth S, Sansom OJ, Ryan KM. Loss of autophagy affects melanoma development in a manner dependent on PTEN status. Cell Death Differ. 2021;28:1437-1439.

Smith RCL, Kanellos G, Vlahov N, Alexandrou C, Willis AE, Knight JRP, Sansom OJ. Translation initiation in cancer at a glance. J Cell Sci. 2021;134:jcs248476.

Sphyris N, Hodder MC, Sansom OJ. Subversion of Niche-Signalling Pathways in Colorectal Cancer: What Makes and Breaks the Intestinal Stem Cell. Cancers (Basel). 2021;13.

2020

Bruens L, Ellenbroek SIJ, Suijkerbuijk SJE, Azkanaz M, Hale AJ, Toonen P, Flanagan DJ, Sansom OJ, Snippert HJ, van Rheenen J. Calorie Restriction Increases the Number of Competing Stem Cells and Decreases Mutation Retention in the Intestine. Cell Rep. 2020;32(3):107937.

Brunton H, Caligiuri G, Cunningham R, Upstill-Goddard R, Bailey UM, Garner IM, Nourse C, Dreyer S, Jones M, Moran-Jones K, Wright DW, Paulus-Hock V, Nixon C, Thomson G, Jamieson NB, McGregor GA, Evers L, McKay CJ, Gulati A, Brough R, Bajrami I, Pettitt SJ, Dziubinski ML, Barry ST, Grützmann R, Brown R, Curry E, Pajic M, Musgrove EA, Petersen GM, Shanks E, Ashworth A, Crawford HC, Simeone DM, Froeling FEM, Lord CJ, Mukhopadhyay D, Pilarsky C, Grimmond SE, Morton JP, Sansom OJ, Chang DK, Bailey PJ, Biankin AV. HNF4A and GATA6 Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer. Cell Rep. 2020;31:107625

Dannhorn A, Kazanc E, Ling S, Nikula C, Karali E, Serra MP, Vorng JL, Inglese P, Maglennon G, Hamm G, Swales J, Strittmatter N, Barry ST, Sansom OJ, Poulogiannis G, Bunch J, Goodwin RJ, Takats Z. Universal Sample Preparation Unlocking Multimodal Molecular Tissue Imaging. Anal Chem. 2020;92(16):11080-11088.

Dreyer SB, Jamieson NB, Morton JP, Sansom OJ, Biankin AV, Chang DK. Pancreatic Cancer: From Genome Discovery to PRECISION-Panc. Clinical oncology (Royal College of Radiologists (Great Britain)). 2020; 32: 5–8

Healy ME, Boege Y, Hodder MC, Böhm F, Malehmir M, Scherr AL, Jetzer J, Chan LK, Parrotta R, Jacob K, Clerbaux LA, Kreutzer S, Campbell A, Gilchrist E, Gilroy K, Rodewald AK, Honcharova-Biletska H, Schimmer R, Vélez K, Büeler S, Cammareri P, Kalna G, Wenning AS, McCoy KD, Gomez de Agüero M, Schulze-Bergkamen H, Klose C, Unger K, Macpherson AJ, Moor AE, Köhler B, Sansom OJ, Heikenwalder M, Weber A. MCL1 is Required for Maintenance of Intestinal Homeostasis and Prevention of Carcinogenesis in Mice. Gastroenterology. 2020; 159: 183-199

Kaymak I, Maier CR, Schmitz W, Campbell AD, Dankworth B, Ade CP, Walz S, Paauwe M, Kalogirou C, Marouf H, Rosenfeldt MT, Gay DM, McGregor GH, Sansom OJ, Schulze A. Mevalonate pathway provides ubiquinone to maintain pyrimidine synthesis and survival in p53-deficient cancer cells exposed to metabolic stress. Cancer research. 2020; 80:189–203

Kennedy SA, Jarboui MA, Srihari S, Raso C, Bryan K, Dernayka L, Charitou T, Bernal-Llinares M, Herrera-Montavez C, Krstic A, Matallanas D, Kotlyar M, Jurisica I, Curak J, Wong V, Stagljar I, LeBihan T, Imrie L, Pillai P, Lynn MA, Fasterius E, Al-Khalili Szigyarto C, Breen J, Kiel C, Serrano L, Rauch N, Rukhlenko O, Kholodenko BN, Iglesias-Martinez LF, Ryan CJ, Pilkington R, Cammareri P, Sansom O, Shave S, Auer M, Horn N, Klose F, Ueffing M, Boldt K, Lynn DJ, Kolch W. Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D). Nature communications. 2020; 11: 499.

Khawaja H, Campbell A, Roberts JZ, Javadi A, O'Reilly P, McArt D, Allen WL, Majkut J, Rehm M, Bardelli A, Di Nicolantonio F, Scott CJ, Kennedy R, Vitale N, Harrison T, Sansom OJ, Longley DB, Evergren E, Van Schaeybroeck S. RALB GTPase: a critical regulator of DR5 expression and TRAIL sensitivity in KRAS mutant colorectal cancer. Cell Death Dis. 2020 Oct 29;11(10):930

Knight JRP, Garland G, Pöyry T, Mead E, Vlahov N, Sfakianos A, Grosso S, De-Lima-Hedayioglu F, Mallucci GR, von der Haar T, Smales CM, Sansom OJ, Willis AE. Control of translation elongation in health and disease. Disease Models & Mechanisms. 2020; 13: dmm043208.

Maniati E, Berlato C, Gopinathan G, Heath O, Kotantaki P, Lakhani A, McDermott J, Pegrum C, Delaine-Smith RM, Pearce OMT, Hirani P, Joy JD, Szabova L, Perets R, Sansom OJ, Drapkin R, Bailey P, Balkwill FR. Mouse Ovarian Cancer Models Recapitulate the Human Tumor Microenvironment and Patient Response to Treatment. Cell reports. 2020; 30: 525-540.e527.

McGregor GH, Campbell AD, Fey SK, Tumanov S, Sumpton D, Rodriguez Blanco G, Mackay G, Nixon C, Vazquez A, Sansom OJ, Kamphorst JJ. Targeting the metabolic response to statin-mediated oxidative stress produces a synergistic anti-tumor response. Cancer research. 2020; 80:175–88

Michalopoulou E, Auciello FR, Bulusu V, Strachan D, Campbell AD, Tait-Mulder J, Karim SA, Morton JP, Sansom OJ, Kamphorst JJ. Macropinocytosis Renders a Subset of Pancreatic Tumor Cells Resistant to mTOR Inhibition. Cell reports. 2020;30:2729-2742.e2724.

Muthalagu N, Monteverde T, Raffo-Iraolagoitia X, Wiesheu R, Whyte D, Hedley A, Laing S, Kruspig B, Upstill-Goddard R, Shaw R, Neidler S, Rink C, Karim SA, Gyuraszova K, Nixon C, Clark W, Biankin AV, Carlin LM, Coffelt SB, Sansom OJ, Morton JP, Murphy DJ. Repression of the Type I Interferon pathway underlies MYC & KRAS-dependent evasion of NK & B cells in Pancreatic Ductal Adenocarcinoma. Cancer discovery. 2020;

Patel R, Brzezinska EA, Repiscak P, Ahmad I, Mui E, Gao M, Blomme A, Harle V, Tan EH, Malviya G, Mrowinska A, Loveridge CJ, Rushworth LK, Edwards J, Ntala C, Nixon C, Hedley A, Mackay G, Tardito S, Sansom OJ, Leung HY. Activation of beta-catenin cooperates with loss of Pten to drive AR-independent castration-resistant prostate cancer. Cancer research. 2020; 80:576–90

Rooney N, Mason SM, McDonald L, Däbritz JHM, Campbell KJ, Hedley A, Howard S, Athineos D, Nixon C, Clark W, Leach JDG, Sansom OJ, Edwards J, Cameron ER, Blyth K RUNX1 is a driver of renal cell carcinoma correlating with clinical outcome Cancer Res. 2020;

Roseweir AK, Park JH, Hoorn ST, Powell AG, Aherne S, Roxburgh CS, McMillan DC, Horgan PG, Ryan E, Sheahan K, Vermeulen L, Paul J, Harkin A, Graham J, Sansom O, Church DN, Tomlinson I, Saunders M, Iveson TJ, Edwards J. Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer. J Path Clin Res. 2020; 6: 283-296

Smith ALM, Whitehall JC, Bradshaw C, Gay D, Robertson F, Blain AP, Hudson G, Pyle A, Houghton D, Hunt M, Sampson JN, Stamp C, Mallett G, Amarnath S, Leslie J, Oakley F, Wilson L, Baker A, Russell OM, Johnson R, Richardson CA, Gupta B, McCallum I, McDonald SAC, Kelly S, Mathers JC, Heer R, Taylor RW, Perkins ND, Turnbull DM, Sansom OJ, Greaves LC. Age-associated mitochondrial DNA mutations cause metabolic remodeling that contributes to accelerated intestinal tumorigenesis. Nature Cancer. 2020; 1:976–989

Wilson DH, Jarman EJ, Mellin RP, Wilson ML, Waddell SH, Tsokkou P, Younger NT, Raven A, Bhalla SR, Noll ATR, Olde Damink SW, Schaap FG, Chen P, Bates DO, Banales JM, Dean CH, Henderson DJ, Sansom OJ, Kendall TJ, Boulter L. Non-canonical Wnt signalling regulates scarring in biliary disease via the planar cell polarity receptors. Nature communications. 2020; 11: 445.

2019

Allen-Petersen BL, Risom T, Feng Z, Wang Z, Jenny ZP, Thoma MC, Pelz KR, Morton JP, Sansom OJ, Lopez CD, Sheppard B, Christensen DJ, Ohlmeyer M, Narla G, Sears RC. Activation of PP2A and inhibition of mTOR synergistically reduce MYC signaling and decrease tumor growth in pancreatic ductal adenocarcinoma. Cancer Res 2019; 79: 209-219

Cosimo E, Tarafdar A, Moles MW, Holroyd AK, Malik N, Catherwood MA, Hay J, Dunn KM, Macdonald AM, Guichard SM, O'Rourke DM, Leach MT, Sansom OJ, Cosulich SC, McCaig AM, et al. AKT/mTORC2 inhibition activates FOXO1 function in CLL cells reducing B cell receptor-mediated survival. Clin Cancer Res 2019; 25: 1574-1587

Gay DM, Ridgway RA, Mueller M, Hodder MC, Hedley A, Clark W, Leach JD, Jackstadt R, Nixon C, Huels DJ, Campbell AD, Bird TG, Sansom OJ. Loss of BCL9/9l suppresses Wnt driven tumourigenesis in models that recapitulate human cancer. Nature communications 2019; 10: 723.

Jackstadt R, van Hooff SR, Leach JD, Cortes-Lavaud X, Lohuis JO, Ridgway RA, Wouters VM, Roper J, Kendall TJ, Roxburgh CS, Horgan PG, Nixon C, Nourse C, Gunzer M, Clark W, Hedley A, Yilmaz OH, Rashid M, Bailey P, Biankin AV, Campbell AD, Adams DJ, Barry ST, Steele CW, Medema JP, Sansom OJ. Epithelial NOTCH Signaling Rewires the Tumor Microenvironment of Colorectal Cancer to Drive Poor-Prognosis Subtypes and Metastasis. Cancer cell. 2019; 36: 19-336.e317.

Johansson J, Naszai M, Hodder MC, Pickering KA, Miller BW, Ridgway RA, Yu Y, Peschard P, Brachmann S, Campbell AD, Cordero JB, Sansom OJ. RAL GTPases Drive Intestinal Stem Cell Function and Regeneration through Internalization of WNT Signalosomes. Cell Stem Cell. 2019; 24: 592-607.e7.

Kugeratski FG, Atkinson SJ, Neilson LJ, Lilla S, Knight JRP, Serneels J, Juin A, Ismail S, Bryant DM, Markert EK, Machesky LM, Mazzone M, Sansom OJ, Zanivan S. Hypoxic cancer-associated fibroblasts increase NCBP2-AS2/HIAR to promote endothelial sprouting through enhanced VEGF signaling. Science signaling 2019; 12. pii: eaan8247.

Leach J, Morton JP, Sansom OJ. Neutrophils: Homing in on the myeloid mechanisms of metastasis. Molecular immunology. 2019;110:69-76.

Liko D, Mitchell L, Campbell KJ, Ridgway RA, Jones C, Dudek K, King A, Bryson S, Stevenson D, Blyth K, Strathdee D, Morton JP, Bird TG, Knight JRP, Willis AE, Sansom OJ. Brf1 loss and not overexpression disrupts tissues homeostasis in the intestine, liver and pancreas. Cell Death Differ. 2019; 26: 2535–2550

Malik N, Dunn KM, Cassels J, Hay J, Estell C, Sansom OJ, Michie AM. mTORC1 activity is essential for erythropoiesis and B cell lineage commitment. Scientific reports. 2019; 9: 16917.

Menon M, Elliott R, Bowers L, Balan N, Rafiq R, Costa-Cabral S, Munkonge F, Trinidade I, Porter R, Campbell AD, Johnson ER, Esdar C, Buchstaller HP, Leuthner B, Rohdich F, et al. A novel tankyrase inhibitor, MSC2504877, enhances the effects of clinical CDK4/6 inhibitors. Scientific reports 2019; 9: 201.

Reader CS, Vallath S, Steele CW, Haider S, Brentnall A, Desai A, Moore KM, Jamieson NB, Chang D, Bailey P, Scarpa A, Lawlor R, Chelala C, Keyse SM, Biankin A, Morton JP, Evans TRJ, Barry ST, Sansom OJ, Kocher HM, Marshall JF. The integrin alphavbeta6 drives pancreatic cancer through diverse mechanisms and represents an effective target for therapy. The Journal of pathology. 2019; 249: 332–342

Rohwer N, Jumpertz S, Erdem M, Egners A, Warzecha KT, Fragoulis A, Kuhl AA, Kramann R, Neuss S, Rudolph I, Endermann T, Zasada C, Apostolova I, Gerling M, Kempa S, Hughes R, Lewis CE, Brenner W, Malinowski MB, Stockmann M, Schomburg L, Faller W, Sansom OJ, Tacke F, Morkel M, Cramer T. Non-canonical HIF-1 stabilization contributes to intestinal tumorigenesis. Oncogene. 2019; 38: 5670-5685.

Spender LC, Ferguson JG, Hughes GD, Davies BR, Goldberg FW, Herrera B, Taylor RG, Strathearn LS, Sansom OJ, Barry ST, Inman GJ. Preclinical evaluation of AZ12601011 and AZ12799734, inhibitors of transforming growth factor beta superfamily type 1 receptors. Mol Pharmacol 2019; 95: 222-234

Schmidt S, Gay D, Uthe FW, Denk S, Paauwe M, Matthes N, Diefenbacher ME, Bryson S, Warrander FC, Erhard F, Ade CP, Baluapuri A, Walz S, Jackstadt R, Ford C, Vlachogiannis G, Valeri N, Otto C, Schulein-Volk C, Maurus K, Schmitz W, Knight JRP, Wolf E, Strathdee D, Schulze A, Germer CT, Rosenwald A, Sansom OJ, Eilers M, Wiegering A. A MYC-GCN2-eIF2alpha negative feedback loop limits protein synthesis to prevent MYC-dependent apoptosis in colorectal cancer. Nature cell biology. 2019; 21: 1413–1424

Vennin C, Melenec P, Rouet R, Nobis M, Cazet AS, Murphy KJ, Herrmann D, Reed DA, Lucas MC, Warren SC, Elgundi Z, Pinese M, Kalna G, Roden D, Samuel M, Zaratzian A, Grey ST, Da Silva A, Leung W, Mathivanan S, Wang Y, Braithwaite AW, Christ D, Benda A, Parkin A, Phillips PA, Whitelock JM, Gill AJ, Sansom OJ, Croucher DR, Parker BL, Pajic M, Morton JP, Cox TR, Timpson P. CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan. Nature communications. 2019; 10: 3637.

2018

Besray Unal E, Kiel C, Benisty H, Campbell A, Pickering K, Bluthgen N, Sansom OJ, Serrano L. Systems level expression correlation of Ras GTPase regulators. Cell Commun Signal. 2018; 16: 46.

Bird TG, Muller M, Boulter L, Vincent DF, Ridgway RA, Lopez-Guadamillas E, Lu WY, Jamieson T, Govaere O, Campbell AD, Ferreira-Gonzalez S, Cole AM, Hay T, Simpson KJ, Clark W, et al. TGFbeta inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence. Sci Transl Med 2018; 10: eaan1230

Burke ZD, Reed KR, Yeh SW, Meniel V, Sansom OJ, Clarke AR, Tosh D. Spatiotemporal regulation of liver development by the Wnt/beta-catenin pathway. Sci Rep 2018; 8: 2735

Candido JB, Morton JP, Bailey P, Campbell AD, Karim SA, Jamieson T, Lapienyte L, Gopinathan A, Clark W, McGhee EJ, Wang J, Escorcio-Correia M, Zollinger R, Roshani R, Drew L, Rishi L, Arkell R, Evans TRJ, Nixon C, Jodrell DI et al. CSF1R(+) Macrophages Sustain Pancreatic Tumor Growth through T Cell Suppression and Maintenance of Key Gene Programs that Define the Squamous Subtype. Cell Rep 2018; 23: 1448-60

Chou A, Froio D, Nagrial AM, Parkin A, Murphy KJ, Chin VT, Wohl D, Steinmann A, Stark R, Drury A, Walters SN, Vennin C, Burgess A, Pinese M, Chantrill LA, et al. Tailored first-line and second-line CDK4-targeting treatment combinations in mouse models of pancreatic cancer. Gut 2018; 67: 2142-55

Conway JRW, Warren SC, Herrmann D, Murphy KJ, Cazet AS, Vennin C, Shearer RF, Killen MJ, Magenau A, Melenec P, Pinese M, Nobis M, Zaratzian A, Boulghourjian A, Da Silva AM, Del Monte-Nieto G, Adam ASA, Harvey RP, Haigh JJ, Wang Y et al. Intravital Imaging to Monitor Therapeutic Response in Moving Hypoxic Regions Resistant to PI3K Pathway Targeting in Pancreatic Cancer. Cell Rep 2018; 23: 3312-26

Ferro R, Adamska A, Lattanzio R, Mavrommati I, Edling CE, Arifin SA, Fyffe CA, Sala G, Sacchetto L, Chiorino G, De Laurenzi V, Piantelli M, Sansom OJ, Maffucci T, Falasca M. GPR55 signalling promotes proliferation of pancreatic cancer cells and tumour growth in mice, and its inhibition increases effects of gemcitabine. Oncogene 2018; 37: 6368–6382

Flanagan DJ, Hodder MC, Sansom OJ. Microenvironmental cues in cancer stemness. Nat Cell Biol 2018; 20: 1102-4.

Foth M, Ismail NFB, Kung JSC, Tomlinson D, Knowles MA, Eriksson P, Sjodahl G, Salmond JM, Sansom OJ, Iwata T. FGFR3 mutation increases bladder tumorigenesis by suppressing acute inflammation. J Pathol 2018; 246: 331-343

Godfrey JD, Morton JP, Wilczynska A, Sansom OJ, Bushell MD. MiR-142-3p is downregulated in aggressive p53 mutant mouse models of pancreatic ductal adenocarcinoma by hypermethylation of its locus. Cell Death Dis 2018; 9: 644

Greenhough A, Bagley C, Heesom KJ, Gurevich DB, Gay D, Bond M, Collard TJ, Paraskeva C, Martin P, Sansom OJ, Malik K, Williams AC. Cancer cell adaptation to hypoxia involves a HIF-GPRC5A-YAP axis. EMBO Mol Med. 2018 10: e8699

Huels DJ, Bruens L, Hodder MC, Cammareri P, Campbell AD, Ridgway RA, Gay DM, Solar-Abboud M, Faller WJ, Nixon C, Zeiger LB, McLaughlin ME, Morrissey E, Winton DJ, Snippert HJ, van Rheenen J, Sansom OJ. Wnt ligands influence tumour initiation by controlling the number of intestinal stem cells. Nat Commun 2018; 9: 1132

Malik N, Sansom OJ, Michie AM. The role of mTOR-mediated signals during haemopoiesis and lineage commitment. Biochem Soc Trans 2018; 46: 1313–1324.

Martin KJ, McGhee EJ, Schwarz JP, Drysdale M, Brachmann SM, Stucke V, Sansom OJ, Anderson KI. Accepting from the best donor; analysis of long-lifetime donor fluorescent protein pairings to optimise dynamic FLIM-based FRET experiments. PLoS One 2018; 13: e0183585

May S, Owen H, Phesse TJ, Greenow KR, Jones GR, Blackwood A, Cook PC, Towers C, Gallimore AM, Williams GT, Sturzl M, Britzen-Laurent N, Sansom OJ, MacDonald AS, Bird AP, Clarke AR, Parry L. Mbd2 enables tumourigenesis within the intestine while preventing tumour-promoting inflammation. J Pathol 2018; 245: 270-82

Monteverde T, Tait-Mulder J, Hedley A, Knight JR, Sansom OJ, Murphy DJ. Calcium signalling links MYC to NUAK1. Oncogene 2018; 37: 982-92

Morris HT, Fort L, Spence HJ, Patel R, Vincent DF, Park JH, Snapper SB, Carey FA, Sansom OJ, Machesky LM. Loss of N-WASP drives early progression in an Apc model of intestinal tumourigenesis. J Pathol 2018; 245: 337-48

Patel R, Fleming J, Mui E, Loveridge C, Repiscak P, Blomme A, Harle V, Salji M, Ahmad I, Teo K, Hamdy FC, Hedley A, van den Broek N, Mackay G, Edwards J, Sansom OJ, Leung HY. Sprouty2 loss-induced IL6 drives castration-resistant prostate cancer through scavenger receptor B1. EMBO Mol Med 2018; 10: e8347

Pearson HB, Li J, Meniel VS, Fennell CM, Waring P, Montgomery KG, Rebello RJ, Macpherson AA, Koushyar S, Furic L, Cullinane C, Clarkson RW, Smalley MJ, Simpson KJ, Phesse TJ, Shepherd PR, Humbert PO, Sansom OJ, Phillips WA. Identification of Pik3ca Mutation as a Genetic Driver of Prostate Cancer That Cooperates with Pten Loss to Accelerate Progression and Castration-Resistant Growth. Cancer Discov 2018; 8: 764-79

Port J, Muthalagu N, Raja M, Ceteci F, Monteverde T, Kruspig B, Hedley A, Kalna G, Lilla S, Neilson L, Brucoli M, Gyuraszova K, Tait-Mulder J, Mezna M, Svambaryte S, Bryson A, Sumpton D, McVie A, Nixon C, Drysdale M et al. Colorectal Tumors Require NUAK1 for Protection from Oxidative Stress. Cancer Discov 2018; 8: 632-47

Vlachogiannis G, Hedayat S, Vatsiou A, Jamin Y, Fernandez-Mateos J, Khan K, Lampis A, Eason K, Huntingford I, Burke R, Rata M, Koh DM, Tunariu N, Collins D, Hulkki-Wilson S, Ragulan C, Spiteri I, Moorcraft SY, Chau I, Rao S et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science 2018; 359: 920-6

Woroniuk A, Porter A, White G, Newman DT, Diamantopoulou Z, Waring T, Rooney C, Strathdee D, Marston DJ, Hahn KM, Sansom OJ, Zech T, Malliri A. STEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap. Nat Commun 2018; 9: 2124

Ahmad I, Sansom OJ. Role of Wnt signalling in advanced prostate cancer. J Pathol 2018; 245: 3-5

Hodder MC, Flanagan DJ, Sansom OJ. Intestinal Stem Cell Dynamics: A Story of Mice and Humans. Cell Stem Cell 2018; 22: 785-7

2017

Azad A, Yin Lim S, D'Costa Z, Jones K, Diana A, Sansom OJ, Kruger P, Liu S, McKenna WG, Dushek O, Muschel RJ, Fokas E. PD-L1 blockade enhances response of pancreatic ductal adenocarcinoma to radiotherapy. EMBO Mol Med 2017; 9: 167-80

Cammareri P, Vincent DF, Hodder MC, Ridgway RA, Murgia C, Nobis M, Campbell AD, Varga J, Huels DJ, Subramani C, Prescott KLH, Nixon C, Hedley A, Barry ST, Greten FR, Inman GJ, Sansom OJ. TGFbeta pathway limits dedifferentiation following WNT and MAPK pathway activation to suppress intestinal tumourigenesis. Cell Death Differ 2017; 24: 1681-93

Carotenuto P, Fassan M, Pandolfo R, Lampis A, Vicentini C, Cascione L, Paulus-Hock V, Boulter L, Guest R, Quagliata L, Hahne JC, Ridgway R, Jamieson T, Athineos D, Veronese A, Visone R, Murgia C, Ferrari G, Guzzardo V, Evans TRJ et al. Wnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers. Gut 2017; 66: 1268-77

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

D'Costa Z, Jones K, Azad A, van Stiphout R, Lim SY, Gomes AL, Kinchesh P, Smart SC, Gillies McKenna W, Buffa FM, Sansom OJ, Muschel RJ, O'Neill E, Fokas E. Gemcitabine-Induced TIMP1 Attenuates Therapy Response and Promotes Tumor Growth and Liver Metastasis in Pancreatic Cancer. Cancer Res 2017; 77: 5952-62

Diamantopoulou Z, White G, Fadlullah MZH, Dreger M, Pickering K, Maltas J, Ashton G, MacLeod R, Baillie GS, Kouskoff V, Lacaud G, Murray GI, Sansom OJ, Hurlstone AFL, Malliri A. TIAM1 Antagonizes TAZ/YAP Both in the Destruction Complex in the Cytoplasm and in the Nucleus to Inhibit Invasion of Intestinal Epithelial Cells. Cancer Cell 2017; 31: 621-34.e6

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: 1728

Fumagalli A, Drost J, Suijkerbuijk SJ, van Boxtel R, de Ligt J, Offerhaus GJ, Begthel H, Beerling E, Tan EH, Sansom OJ, Cuppen E, Clevers H, van Rheenen J. Genetic dissection of colorectal cancer progression by orthotopic transplantation of engineered cancer organoids. Proc Natl Acad Sci U S A 2017; 114: E2357-E2364

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

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

Kersemans V, Beech JS, Gilchrist S, Kinchesh P, Allen PD, Thompson J, Gomes AL, D'Costa Z, Bird L, Tullis IDC, Newman RG, Corroyer-Dulmont A, Falzone N, Azad A, Vallis KA, Sansom OJ, Muschel RJ, Vojnovic B, Hill MA, Fokas E et al. An efficient and robust MRI-guided radiotherapy planning approach for targeting abdominal organs and tumours in the mouse. PLoS One 2017; 12: e0176693

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: 372-376

Myant KB, Cammareri P, Hodder MC, Wills J, Von Kriegsheim A, Gyorffy B, Rashid M, Polo S, Maspero E, Vaughan L, Gurung B, Barry E, Malliri A, Camargo F, Adams DJ, Iavarone A, Lasorella A, Sansom OJ. HUWE1 is a critical colonic tumour suppressor gene that prevents MYC signalling, DNA damage accumulation and tumour initiation. EMBO Mol Med 2017; 9: 181-97

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

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

Rose AM, Sansom OJ, Inman GJ. Loss of TGF-beta signaling drives cSCC from skin stem cells - More evidence. Cell Cycle 2017; 16: 386-87

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

Tian A, Benchabane H, Wang Z, Zimmerman C, Xin N, Perochon J, Kalna G, Sansom OJ, Cheng C, Cordero JB, Ahmed Y. Intestinal stem cell overproliferation resulting from inactivation of the APC tumor suppressor requires the transcription cofactors Earthbound and Erect wing. PLoS Genet 2017; 13: e1006870

van der Weyden L, Arends MJ, Campbell AD, Bald T, Wardle-Jones H, Griggs N, Velasco-Herrera MD, Tuting T, Sansom OJ, Karp NA, Clare S, Gleeson D, Ryder E, Galli A, Tuck E, Cambridge EL, Voet T, Macaulay IC, Wong K, Sanger Mouse Genetics P et al. Genome-wide in vivo screen identifies novel host regulators of metastatic colonization. Nature 2017; 541: 233-6

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:eaai8504.

Wildenberg ME, Koelink PJ, Diederen K, Te Velde AA, Wolfkamp SC, Nuij VJ, Peppelenbosch MP, Nobis M, Sansom OJ, Anderson KI, van der Woude CJ, D'Haens GR, van den Brink GR. The ATG16L1 risk allele associated with Crohn's disease results in a Rac1-dependent defect in dendritic cell migration that is corrected by thiopurines. Mucosal Immunol 2017; 10: 352-60

Huels DJ, Sansom OJ. R-spondin Is More Than Just Wnt's Sidekick. Dev Cell 2017; 41: 456-8

Jackstadt R, Sansom OJ. The Wae to repair: prostaglandin E2 (PGE2) triggers intestinal wound repair. EMBO J 2017; 36: 3-4

Morton JP, Sansom OJ. CXCR2 inhibition in pancreatic cancer: opportunities for immunotherapy? Immunotherapy 2017; 9: 9-12

Phesse TJ, Durban VM, Sansom OJ. Defining key concepts of intestinal and epithelial cancer biology through the use of mouse models. Carcinogenesis 2017; 38: 953-65

Phesse TJ, Sansom OJ. Lgr5 joins the club of gastric stem cell markers in the corpus. Nat Cell Biol 2017; 19: 752-4

2016

Ahmad I, Mui E, Galbraith L, Patel R, Tan EH, Salji M, Rust AG, Repiscak P, Hedley A, Markert E, Loveridge C, van der Weyden L, Edwards J, Sansom OJ, Adams DJ, Leung HY. Sleeping Beauty screen reveals Pparg activation in metastatic prostate cancer. Proc Natl Acad Sci USA. 2016; 113: 8290-5

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 et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;  531: 47-52

Birch J, Clarke CJ, Campbell AD, Campbell K, Mitchell L, Liko D, Kalna G, Strathdee D, Sansom OJ, Neilson M, Blyth K, Norman JC. The initiator methionine tRNA drives cell migration and invasion leading to increased metastatic potential in melanoma. Biol Open. 2016; 5: 1371-9,

Cammareri P, Rose AM, Vincent DF, Wang J, Nagano A, Libertini S, Ridgway RA, Athineos D, Coates PJ, McHugh A, Pourreyron C, Dayal JH, Larsson J, Weidlich S, Spender LC, Sapkota GP, Purdie KJ, Proby CM, Harwood CA, Leigh IM et al. Inactivation of TGFbeta receptors in stem cells drives cutaneous squamous cell carcinoma. Nature communications. 2016; 7: 12493

Cheung EC, Lee P, Ceteci F, Nixon C, Blyth K, Sansom OJ, Vousden KH. Opposing effects of TIGAR- and RAC1-derived ROS on Wnt-driven proliferation in the mouse intestine. Genes Dev. 2016; 30: 52-63

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

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. mTORC2 signaling drives the development and progression of pancreatic cancer. Cancer Res. 2016; 76: 6911-23

Elbediwy A, Vincent-Mistiaen ZI, Spencer-Dene B, Stone RK, Boeing S, Wculek SK, Cordero J, Tan EH, Ridgway R, Brunton VG, Sahai E, Gerhardt H, Behrens A, Malanchi I, Sansom OJ, Thompson BJ. Integrin signalling regulates YAP and TAZ to control skin homeostasis. Development. 2016; 143: 1674-87

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 et al. 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. 2016; 14: 152-67

Gao Y, Vincent DF, Davis AJ, Sansom OJ, Bartholin L, Li Q. Constitutively active transforming growth factor beta receptor 1 in the mouse ovary promotes tumorigenesis. Oncotarget. 2016; 7: 40904-18

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. Notch3 drives development and progression of cholangiocarcinoma. Proc Natl Acad Sci USA. 2016; 113: 12250-5

Jackstadt R, Sansom OJ. Mouse models of intestinal cancer. J Pathol. 2016; 238: 141-51

Koppens MA, Bounova G, Cornelissen-Steijger P, de Vries N, Sansom OJ, Wessels LF, van Lohuizen M. Large variety in a panel of human colon cancer organoids in response to EZH2 inhibition. Oncotarget. 2016; 7: 69816-28

Kumar N, Srivillibhuthur M, Joshi S, Walton KD, Zhou A, Faller WJ, Perekatt AO, Sansom OJ, Gumucio DL, Xing J, Bonder EM, Gao N, White E, Verzi MP. A YY1-dependent increase in aerobic metabolism is indispensable for intestinal organogenesis. Development. 2016; 143: 3711-22

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  RelA regulates CXCL1/CXCR2-dependent oncogene-induced senescence in murine Kras-driven pancreatic carcinogenesis. J Clin Invest. 2016; 126: 2919-32

Marusiak AA, Stephenson NL, Baik H, Trotter EW, Li Y, Blyth K, Mason S, Chapman P, Puto LA, Read JA, Brassington C, Pollard HK, Phillips C, Green I, Overman R, Collier M, Testoni E, Miller CJ, Hunter T, Sansom OJ et al. Recurrent MLK4 Loss-of-Function Mutations Suppress JNK Signaling to Promote Colon Tumorigenesis. Cancer Res. 2016; 76: 724-35

Sinclair A, Park L, Shah M, Drotar M, Calaminus S, Hopcroft LEM, Kinstrie R, Guitart AV, Dunn K, Abraham SA, Sansom O, Michie AM, Machesky L, Kranc KR, Graham GJ, Pellicano F, Holyoake TL. CXCR2 and CXCL4 regulate survival and self-renewal of hematopoietic stem/progenitor cells. Blood. 2016; 128: 371-83

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 et al. CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma. Cancer Cell. 2016; 29: 832-45

Wormann SM, Song L, Ai JY, Diakopoulos KN, Kurkowski MU, Gorgulu K, Ruess D, Campbell A, Doglioni C, Jodrell D, Neesse A, Demir IE, Karpathaki AP, Barenboim M, Hagemann T, Rose-John S, Sansom O, Schmid RM, Protti MP, Lesina M, Algül H. Loss of p53 function activates JAK2-STAT3 signaling to promote pancreatic tumor growth, stroma modification, and gemcitabine resistance in mice and is associated with patient survival. Gastroenterology. 2016; 151: 180-93,

Images

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Lab Members

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Associate Scientist

Andrew Campbell

Postdoctoral Scientists

Constantinos Alexandrou
Holly Brunton
Dustin Flanagan
Nuray Gunduz
Arafath Kaja Najumudeen
Georgios Kanellos
John Knight
Tamsin Lannagan
Noha Mohamed
Alexander Raven
Johan Vande Voorde
Nikola Vlahov

Principal Scientific Officer

Rachel Ridgway

Senior Scientific Officers

Xabier Cortes Lavaud
Catriona Ford
Kathryn Gilroy
Brenda McGuire

Scientific Officer

Tam Jamieson

Clinical Research Fellows

Michael Gillespie
Mark White

PhD Students

Sigrid Fey (Pancreatic Cancer UK Future Leaders Academy)
Ella Gilchrist
Reshmi Nair
Rachael Smith (Pancreatic Cancer UK Future Leaders Academy) 
Teena Thakur (joint with Ross Cagan)
Lucas Zeiger

Science Writer

Nathalie Sphyris

Research

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Read more about the Research Groups working at the Beatson Institute.

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Seminars

Seminars 2021

Find out more about our seminars including our Distinguished Seminar Programme.

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