Grant: CAG/ CCFC/CIHR Rx&D New Investigator Salary Award

Canada has the highest rate of inflammatory bowel disease in the world with 1 in 200 Canadians suffering with IBD. Disease is characterized by unchecked inflammation that leads to a cycle of tissue damage and healing. The repeated damage and healing process also leads to fibrosis causing stricture formation in patients that frequently requires surgey. I study a specific type of immune cell called a macrophage. Macrophages are key players in the inflammatory process. In fact, they are the largest producer of TNFalpha in the gut and an anti-TNFalpha antibody, Remicaid, has proven to be a very effective treatment for IBD. Normally when macrophages are finished their job in inflammation, they convert to a healer cell that assists in the resolution of inflammation. A key switch that happens in macrophages is dictated by how they use the amino acid L-arginine. L-arginine can be metabolized by two pathways, one that leads to inflammation and one that promotes healing. I am proposing to manipulate the metabolism of L-arginine in macrophages during IBD to stop the inflammatory process and to stop the fibrosis that can lead to stricture formation. If we can force L-arginine metabolism down the correct pathway, we may be able to use it to stop the inflammatory process that is the root of IBD. In addition, we may be able to manipulate this pathway to prevent fibrosis and stricture formation and avoid the need for surgical intervention to correct these serious complications in patients with IBD.