Improving Patient Stratification and Treatment

Dr Annabelle Lewis is a Group Leader based at the Wellcome Trust Centre for Human Genetics. Annabelle studied Natural Sciences at the University of Cambridge as an undergraduate, and went on to completed a PhD and postdoc at Dr Wolf Reik’s laboratory in the Babraham Institute, investigating the epigenetic regulation of imprinted genes. She then moved to work on the genetics of colorectal cancer in Prof Ian Tomlinson’s laboratory in the CRUK London Research Institute and subsequently the Wellcome Centre for Human Genetics (within the Nuffield Department of Medicine). Annabelle is investigating the functional roles of cancer risk variants of colorectal cancer in gene regulation, specifically their role in regulating methylation in the promoter of the DNA repair gene MLH1.

There are currently over 100 common genetic variants associated with an increased risk of colorectal cancer. However most of this information has yet to be usefully translated into the clinic. Most of the DNA variants that increase colorectal cancer risk do not mutate protein sequences. It is presumed that they modify the levels of gene activity and the amount of protein produced. The aim of Annabelle’s research is to find out the target gene of each variant, whether the risk variant turns this gene up or down, how it does this and then why different amounts of the gene product increase the chance of cancer. This knowledge will identify gene products that can be targeted with existing therapy or novel drug targets. It will also help to stratify cancer patients into groups which will respond well or poorly to therapeutic regimes. They also aim to identify groups of the population who would benefit from increased or early screening. Ultimately, this will help patients receive the most effective and appropriate treatment for their individual cancer.

Within Oxford, Annabelle is collaborating with Dr David Church, Prof Catharine Green and Prof Simon Leedham (Wellcome Trust Centre for Human Genetics), Prof Timothy Maughan and Prof Eric O’Neill (Department of Oncology), Prof Gareth Bond, Prof Skirmantas Kriaucionis and Dr Benjamin Schuster-Böckler (Ludwig Institute for Cancer Research).
Further collaborators are Prof Ian Tomlinson, Dr Roland Arnold and Dr Claire Palles (University of Birmingham), and Prof Daniela Furlan (Università dell’Insubria Varese, Italy).

Annabelle’s research is funded through the New Investigator Research Grant from the Medical Research Council and a MRC Harwell IMPC grant.