The focus and long-term research goals of the Sonnenberg Laboratory are to interrogate the mechanisms by which the mammalian immune system controls tissue homeostasis, immunity, inflammation and cancer at mucosal barrier surfaces of the body. This is a considerable challenge given the enormous surface area of these sites, such as the gastrointestinal tract, which is home to an estimated 10 trillion microbes (termed the microbiota) and a majority of our body’s total immune system. While interactions between mammalian hosts and microbiota are normally beneficial, these interactions must be tightly regulated to prevent chronic inflammation. Studies in patient populations indicate that abnormal host immune responses to microbiota are causally-linked to the pathogenesis and progression of numerous chronic disorders, including inflammatory bowel disease (IBD), HIV/AIDS, viral hepatitis, cardiovascular disease, multiple sclerosis, Alzheimer’s diseases, autism, obesity, diabetes and cancer. Further, these interactions can influence the success or failure of multiple clinical therapies. Ongoing research in the Sonnenberg Laboratory aims to (1) interrogate the pathways that regulate normally beneficial host interactions with microbiota; (2) determine how these pathways become disrupted in multiple chronic human diseases; and (3) identify novel preventative, therapeutic or curative approaches to target the immune system and/or microbiota to benefit human health.