SUMMARY: The inflammatory bowel diseases (IBD), typically classified as Crohn’s disease (CD) or ulcerative colitis (UC), are chronic intestinal disorders characterized by dysregulated host immune responses to the gut microbiota in genetically susceptible hosts. IBD affects 1.4 million people in the United States and it is estimated that the frequency will continue to increase, resulting in substantial costs related to medical and surgical therapy as well as lost work productivity, disability, and morbidity for patients. In this proposal, we will develop a sequencing- based approach to analyze blood and tissue samples from patients with ulcerative colitis in an effort to identify new determinants involved in the pathogenesis of this disease.