Prof. Ann Williams
WELCOME TO THE COLORECTAL TUMOUR GROUP
The Williams lab are interested in improving prevention and treatment of colorectal tumorigenesis.
Epidemiological evidence suggests that 50-80% of bowel cancer deaths could be prevented. Improving cancer survival and the lives of patients is one of the key driving forces behind biomedical research at the University of Bristol, laying the foundation for better patient outcomes.
Mission and Impact
Colorectal (bowel) cancer remains the second most common cause of cancer deaths in the UK. Survival rates for bowel cancer have been improving over the past 20 years thanks to increased early screening and advancements in research. However, with changing lifestyles and increasing levels of obesity, there is likely to be a global increase in the number of people developing this type of cancer. Both prevention and treatment are therefore at the heart of our research.
This research aims to understand the mechanisms that drive early tumorigenesis and how they impact response of colorectal cancers to conventional therapies. Research is translated to the clinic through collaboration with colleagues in the UHBristol NHS Foundation Trust and other hospitals in the South West. More info.
The University of Bristol’s Colorectal Tumour Biology (CTB) group, led by Professor Ann Williams, is currently investigating the impact of inflammation on colon cancer stem cell biology, and whether cancer stem cells can be targeted with non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin. As well as their potential importance in prevention, the CTB group believe that identifying and targeting drivers of stem cell plasticity have significant potential as new therapeutic targets. As part of this approach they are focusing on the atypical NF-kappaB pathway as a driver of the outgrowth of early cancer cells with deregulated β-catenin signalling.
Their research uses cross-comparison of data from unique human tumour models, clinical samples and state-of-the-art epidemiology, used to investigate the impact of in vitro findings on cancer risk and prognosis in large patient cohorts.
Legge D, Shephard A, Collard TJ, Morgan RG, Paraskeva C and Williams AC. Identification of BCL-3 as a novel regulator of β-catenin activity, driving the colorectal cancer stem cell-like phenotype. Disease, Methods and Mechanisms 2019 (in press).
Morgan RG, Ridsdale J, Payne M, Heesom KJ, Wilson MC, Davidson A, Greenhough A, Davies S, Williams AC, Blair A, Waterman ML, Tonks A, Darley RL. LEF-1 drives aberrant β-catenin nuclear localization in myeloid leukemia cells. Haematologica. 2019 Jan 10. pii: haematol.2018.202846.
Greenhough A, Bagley C, Collard TJ, Heesom KJ, Gurevich DJ, Gay D, Martin P, Sansom OJ, Malik KT, Paraskeva C and Williams AC. Cancer cell adaptation to hypoxia requires HIF-driven GPRC5A-YAP activity. EMBO Molecular Medicine, 2018 Nov;10(11). pii: e8699.
Morgan RG, Mortensson E, Legge DN, Gupta B, Collard TJ, Greenhough A, Williams AC. LGR5 expression is regulated by EGF in early colorectal adenomas and governs EGFR inhibitor sensitivity. Br J Cancer. 2018 118(4):558-565.
Gash KJ, Chambers AC, Cotton DE, Williams AC, Thomas MG. Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy. Br J Cancer. 2017 117(2):210-219.
Urban BC, Collard TJ, Eagle CJ, Southern SL, Morgan RG, Greenhough A, H-Zadeh M, Gosh A, Poulsom R, Silver AJ, Paraskeva C and Williams AC. BCL-3 promotes colorectal tumour cell survival through activation of the AKT signalling pathway. Gut, 2016; 65(7):1151-64.