The focus and long-term research goals of the Sonnenberg Laboratory are to interrogate the mechanisms that maintain a state of health in the human gastrointestinal tract. This is a considerable challenge given the enormous surface area of this organ in which a single layer of intestinal epithelial cells segregates an estimated 100 trillion commensal bacteria from a significant portion of our bodies total immune system. While interactions between mammalian hosts and commensal bacteria are normally beneficial, it is becoming increasingly clear the dysregulated interactions can result in chronic inflammation. Further, emerging studies in patient populations indicate that abnormal host immune responses to commensal bacteria are causally-linked to the pathogenesis and progression of numerous chronic infectious, inflammatory and metabolic diseases, including inflammatory bowel disease (IBD), HIV/AIDS, viral hepatitis, cardiovascular disease, obesity, diabetes and cancer. Ongoing research in the Sonnenberg Laboratory aims to (1) interrogate the pathways that regulate normally beneficial host interactions with commensal bacteria, (2) determine how these pathways become disrupted in chronic human diseases, and (3) identify novel therapeutic targets to prevent or limit dysregulated host-commensal bacteria relationships in human disease.