Grant: Project Grant

Inflammatory bowel disease (IBD) affects 1 in 140 Canadians. It is caused by inflammation along the gastrointestinal (GI) tract that can lead to symptoms including abdominal pain, vomiting, and diarrhea. There are two main types of IBD, Crohn's disease (CD) and ulcerative colitis (UC). In CD, GI inflammation can lead to a very serious complication called fibrosis. Fibrosis occurs because repeated cycles of inflammation and healing cause scarring that prevents the intestine from working properly and can even cause intestinal blockages. 1 in 3 people with CD develop fibrosis within 10 years of diagnosis and require surgery to remove the diseased bowel. The use of new biological therapies has revolutionized treatment for intestinal inflammation in CD but has not reduced the number of people, who go on to develop fibrosis. It may be that small amounts of subclinical inflammation are enough to kick start the development of fibrosis. Unfortunately, we do not have any drugs to prevent of treat intestinal fibrosis. My laboratory has developed a mouse model that mimics key features of CD, including intestinal fibrosis. Mice that are missing an enzyme called "SHIP" develop CD-like intestinal inflammation and fibrosis. We have also found that some people with CD have very low SHIP levels and those people have more severe disease and require more surgeries. Using two mouse models, we will identify key proteins that drive intestinal fibrosis. We will target those proteins to see if we can reduce intestinal fibrosis in mice. We will also examine SHIP and fibrosis-inducing proteins in blood and biopsy specimens from people with CD, who have intestinal fibrosis. This is exciting because there is already a drug on the market (idelalisib) that can be used to target one of the fibrosis-inducing proteins that we have identified. Our research could be rapidly translated into a 'first-in-kind' therapy to treat fibrosis in people with CD.