Clonal Dynamics in Cancer
Group Leader:
Dr Alex Raven
Cancer initiation and progression depend on the selection of cancerous clones within an organ and tissue. Propagation of these bad acting populations usually relies on stem cells generating progeny that out compete and replace neighbouring, normal, cells. Interestingly in the liver there is no professional stem cell population, all cells have the potential to divide and produce new cells. Furthermore, cancer causing genetic mutations do not provide an obvious competitive advantage and are not sufficient to drive tumour formation and eventual hepatocellular carcinoma.
The goal of our laboratory is to understand the key signalling pathways that regulate clonal growth in the liver and how they become perturbed during disease. Using advanced, preclinical models of liver disease, we focus on how pre-cancerous disease selects the bad acting cells that go on to form cancer. From this research we can then develop therapeutic interventions and early detection assays that will prevent hepatocellular carcinoma and reduce the number of patients developing late-stage disease.
Lab Reports
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Recent Publications
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Lab Members
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Recent Publications
2026
Alexander Raven, Kathryn Gilroy, Hu Jin, Joseph A Waldron, Holly Leslie, June Munro, Holly Hall, Rachel A Ridgway, Catriona A Ford, Doga C Gulhan, Nikola Vlahov, Megan L Mills, Andrew Hartley, Eve Anderson, Sheila Bryson, Nathalie Sphyris, Miryam Müller, Stephanie May, Barbara Cadden, Colin Nixon, Scott H Waddell, Rachel Guest, Luke Boulter, Nick Barker, Hans Clevers, Hao Zhu, Johanna Ivaska, Douglas Strathdee, Crispin J Miller, Nigel B Jamieson, Martin Bushell, Peter J Park, Thomas G Bird, Owen J Sansom. Hepatic zonation determines tumorigenic potential of mutant β-catenin. Nature, 2026, 649, 739-748.
Georgios Kanellos, Chiara Giacomelli, Alexander Raven, Nikola Vlahov, Hu Jin, Pauline Herviou, Sudhir B. Malla, Nadia Nasreddin, Patricia P. Centeno, Constantinos Alexandrou, Kathryn Gilroy, Rachel L. Baird, Kathryn Pennel, June Munro, Joseph A. Waldron, Holly Hall, Leah Officer-Jones, Sheila Bryson, Douglas Strathdee, Sergio Lilla, Sara Zanivan, Vivienne Morrison, Colin Nixon, Rachel A. Ridgway, Crispin Miller, John R. P. Knight, Andrew D. Campbell, Philip D. Dunne, John Le Quesne, Joanne Edwards, Peter J. Park, Martin Bushell & Owen J. Sansom. Nucleophosmin supports WNT-driven hyperproliferation and tumor initiation. Nature Genetics, 2026, 58, 100-115.
Mark White, Megan L. Mills, Laura M. Millett, Kathryn Gilroy, Yourae Hong, Lucas B. Zeiger, Rosalin J. Simpson, Shania M. Corry, Amelia Ligeza, Tamsin R. M. Lannagan, Susanti Susanti, Rachel A. Ridgway, Ayse S. Yazgili, Lucile Grzesiak, Raheleh Amirkhah, Catriona A. Ford, Nikola Vlahov, Hannah Tovell, Leah Officer-Jones, Catherine Ficken, Rachel Pennie, Arafath K. Najumudeen, Alexander Raven, Nadia Nasreddin, Ekansh Chauhan, Andrew S. Papanastasiou, Colin Nixon, Vivienne Morrison, Rene Jackstadt, Janet S. Graham, Crispin J. Miller, Sarah J. Ross, Simon T. Barry, Valeria Pavet, Richard H. Wilson, John Le Quesne, Philip D. Dunne, Sabine Tejpar, Simon Leedham, Andrew D. Campbell & Owen J. Sansom. MAPK-driven epithelial cell plasticity drives colorectal cancer therapeutic resistance. Nature, 2026, 650, 748-758.
2023
Johan Vande Voorde, Rory T. Steven, Arafath K. Najumudeen, Catriona A. Ford, Alex Dexter, Ariadna Gonzalez-Fernandez, Chelsea J. Nikula, Yuchen Xiang, Lauren Ford, Stefania Maneta Stavrakaki, Kathryn Gilroy, Lucas B. Zeiger, Kathryn Pennel, Phimmada Hatthakarnkul, Efstathios A. Elia, Ammar Nasif, Teresa Murta, Eftychios Manoli, Sam Mason, Michael Gillespie, Tamsin R. M. Lannagan, Nikola Vlahov, Rachel A. Ridgway, Colin Nixon, Alexander Raven, Megan Mills, Dimitris Athineos, Georgios Kanellos, Craig Nourse, David M. Gay, Mark Hughes, Amy Burton, Bin Yan, Katherine Sellers, Vincen Wu, Kobe De Ridder, Engy Shokry, Alejandro Huerta Uribe, William Clark, Graeme Clark, Kristina Kirschner, Bernard Thienpont, Vivian S. W. Li, Oliver D. K. Maddocks, Simon T. Barry, Richard J. A. Goodwin, James Kinross, Joanne Edwards, Mariia O. Yuneva, David Sumpton, Zoltan Takats, Andrew D. Campbell, Josephine Bunch & Owen J. Sansom. Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target. Nature Metabolism, 2023, 5, 1303–1318.
2021
Dustin J. Flanagan, Nalle Pentinmikko, Kalle Luopajärvi, Nicky J. Willis, Kathryn Gilroy, Alexander P. Raven, Lynn Mcgarry, Johanna I. Englund, Anna T. Webb, Sandra Scharaw, Nadia Nasreddin, Michael C. Hodder, Rachel A. Ridgway, Emma Minnee, Nathalie Sphyris, Ella Gilchrist, Arafath K. Najumudeen, Beatrice Romagnolo, Christine Perret, Ann C. Williams, Hans Clevers, Pirjo Nummela, Marianne Lähde, Kari Alitalo, Ville Hietakangas, Ann Hedley, William Clark, Colin Nixon, Kristina Kirschner, E. Yvonne Jones, Ari Ristimäki, Simon J. Leedham, Paul V. Fish, Jean-Paul Vincent, Pekka Katajisto & Owen J. Sansom. NOTUM from Apc-mutant cells biases clonal competition to initiate cancer. Nature, 2021, 594, 430–435.
2020
D. H. Wilson, E. J. Jarman, R. P. Mellin, M. L. Wilson, S. H. Waddell, P. Tsokkou, N. T. Younger, A. Raven, S. R. Bhalla, A. T. R. Noll, S. W. Olde Damink, F. G. Schaap, P. Chen, D. O. Bates, J. M. Banales, C. H. Dean, D. J. Henderson, O. J. Sansom, T. J. Kendall & L. Boulter. Non-canonical Wnt signalling regulates scarring in biliary disease via the planar cell polarity receptors. Nature Communications, 2020, 11. Article number: 445.
2019
Luigi Aloia, Mikel Alexander McKie, Grégoire Vernaz, Lucía Cordero-Espinoza, Niya Aleksieva, Jelle van den Ameele, Francesco Antonica, Berta Font-Cunill, Alexander Raven, Riccardo Aiese Cigliano, German Belenguer, Richard L. Mort, Andrea H. Brand, Magdalena Zernicka-Goetz, Stuart J. Forbes, Eric A. Miska and Meritxell Huch. Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration. Nature Cell Biology, 2019, 21, 1321-1333.
2018
Sofia Ferreira-Gonzalez, Wei-Yu Lu, Alexander Raven, Benjamin Dwyer, Tak Yung Man, Eoghan O’Duibhir, Philip J. Starkey Lewis, Lara Campana, Tim J. Kendall et al., Stuart J. Forbes. Paracrine cellular senescence exacerbates biliary injury and impairs regeneration. Nature Communications, 2018, 9:1020.
Shantisree Sandeepani Rayagiri, Daniele Ranaldi, Alexander Raven, Nur Izzah Farhana Mohamad Azhar, Olivier Lefebvre, Peter S Zammit and Anne-Gaëlle Borycki. Basal lamina remodelling at the skeletal muscle stem cell niche mediates stem cell self-renewal. Nature Communications, 2018, 9:1075.
2017
Alexander Raven, Wei-Yu Lu, Tak Yung Man, Sofia Ferreira-Gonzalez, Eoghan O’Duibhir, Benjamin Dwyer, John P Thomson, Richard R Meehan, Roman Bogorad et al., Stuart J Forbes. Cholangiocytes act as Facultative Liver Stem Cells during Impaired Hepatocyte Regeneration. Nature, 2017, 547, 350-354.
2016
Rachel V. Guest, Luke Boulter, Benjamin J. Dwyer, Timothy J. Kendall, Tak-Yung Man, Sarah E. Minnis-Lyons, Wei-Yu Lu, Andrew J. Robson, Sofia Ferreira Gonzalez, Alexander Raven et al., Stuart J. Forbes. Notch3 drives development and progression of cholangiocarcinoma. PNAS, 2016, vol. 113, no. 43, 12250-12255.
2015
Wei-Yu Lu, Thomas G. Bird, Luke Boulter, Atsunori Tsuchiya, Alicia M. Cole, Trevor Hay, Rachel V. Guest, Davina Wojtacha, Tak Yung Man, Alison Mackinnon, Rachel A. Ridgway, Timothy Kendall, Michael J. Williams, Thomas Jamieson, Alex Raven et al., Stuart J. Forbes. Hepatic progenitor cells of biliary origin with liver repopulation capacity. Nature Cell Biology, 2015, 17, 971–983.
