Grant: Project Grant

The inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, affect over 200,000 Canadians. These are lifelong, debilitating conditions that have no clear cause, no cure, and which have significant costs to the health care system and patient quality of life. For unknown reasons, Canada has the highest incidence of IBD in the world. Unfortunately, current therapies are costly, ineffective for some patients, and can have serious side effects. We need to understand the underlying causes of IBD so that we can develop better treatments and, ultimately, find a cure. Our research team is studying the epithelium, the layer of cells that lines the intestinal wall and which provides an important barrier between the trillions of bacteria in the intestinal lumen and the immune system of the intestine. Over-activation of the immune system by gut bacteria plays an important role in IBD. We know that the epithelial barrier breaks down in IBD, and we think this may be an important contributor to these diseases. We hypothesize that a specific type of protein receptor on epithelial cells, protease-activated receptor 2 (PAR2), may play a role in the resolution of the inflammatory response and speed healing. In this proposal, we have set three aims to test our hypothesis. First, we are going to measure the enzymes that activate PAR2 in IBD tissue. We will then see if they act through PAR2 to turn on genes that control the healing process. Second, we are going to use new cell culture methods in epithelial cells derived from mouse intestine and intestinal biopsies from consenting IBD patients to determine how PAR2 alters epithelial cell behaviour, especially cell migration, to speed healing. Third, we are going to test these PAR2-mediated effects in mouse models of disease, to see if they are appropriate targets for therapy. Ultimately, our proposed research will identify avenues for the development of new treatments for IBD.