Grant: CIHR Fellowship

Inflammatory Bowel Disease (IBD) is a chronic condition characterized by severe inflammation of the intestine. There are two main forms of IBD: Crohn's Disease (CD) and Ulcerative Colitis (UC). 1 in 150 Canadians is living with CD or UC, one of the highest rates worldwide. IBD disrupts an individual's ability to digest food, absorb nutrition and eliminate waste in a normal manner, placing enormous health and financial burden on individuals. There are currently no specific treatments for IBD. SP140, a protein that recognizes modifications on the proteins packaging the DNA, has been recently shown to have important ramifications in CD. A single nucleotide mutation found in SP140 was significantly associated with CD risk in a study analyzing control and CD patients. The role of SP140 in CD pathogenesis has never been previously studied and is the objective of our study. Given it is highly expressed in immune cells and has various domains for DNA recognition, this protein holds promise to critically regulate inflammation in CD. We will assess the role of SP140 in CD in healthy control and CD patients. We will further investigate what each of the different domains in the SP140 protein is responsible for. Lastly, we will study the role of SP140 in a preclinical model of CD in order to clearly establish its role in modulating immune responses. SP140 belongs to a family of proteins that have received a lot of attention in their role to regulate inflammation. Inhibition of these proteins have been shown to be therapeutically relevant in the setting of inflammation. The proposed research will further our understanding of the mechanisms underlying IBD and present potentially novel therapeutic strategy which will be critical in tackling the increasing IBD incidence in Canada.