Our Division studies mechanisms that underpin gastrointestinal and liver diseases. One specific focus is on inflammatory bowel disease, but our research covers a much wider range of GI diseases.
Crohn’s disease and ulcerative colitis are both inflammatory bowel diseases (IBD). The prevalence of these conditions has profoundly increased over the last decades. While originally mostly diseases of the ‘Western World’, they are now recognised globally, with the UK featuring one of the highest prevalence rates in the world. Our research has made substantial contributions to the discovery of the genomic risk landscape, and hence the hereditary component of Crohn’s disease and ulcerative colitis. The basis for this has been the assembly of large patient cohorts, the latest iteration of which is the UK IBD BioResource, where patients have agreed to be recalled for further studies based on factors such as their presentation of disease biomarkers As with many other complex diseases, only a small number of these genomic risk genes is understood, a prerequisite to gain mechanistic insights. Our research has provided important leaps forward regarding cellular major pathways that are affected by genetics. For example, we have found how autophagy and endoplasmic reticulum stress drive the disease process, and discovered entirely novel immunometabolic circuits that are important in Crohn’s disease. We also explore how these pathways interact with each other and how environmental factors may trigger the disease process in genetically-susceptible individuals. Biomarkers that have been identified by our research can predict the severity of disease at diagnosis and reveal biological mechanisms that determine the severity of the disease. The new mechanistic insights that are informed by these studies translate into new therapies, with investigators contributing to phase Ib and phase IIa/b studies, and the design and execution of large global phase III trials.
We also have interests in diseases other than IBD. For example, our investigators have discovered how aldehydes damage DNA and what implications this has for alcohol-related liver disease, and for bone marrow and tumour formation. By studying new treatments for the deadly liver disease alcoholic hepatitis, we have discovered key mediators that drive liver damage in this acute condition. We have also made important contributions in understanding the genomic risk landscape of primary sclerosing cholangitis and primary biliary cirrhosis, for which a national BioResource has been assembled. Affiliated researchers have also pioneered innovative strategies to survey Barrett’s oesophagus, a pre-malignant condition that can lead to oesophageal adenocarcinoma, and have made key contributions to the Cancer Genome Atlas for this latter disease.
