Pew Charitable Trust Award

Hundreds of trillions of microorganisms live as an integral part of our body. In the gut, 'commensal' bacteria form an evolutionarily established microbial community with vital metabolic, physiological and protective immune functions. Dysregulation of this commensal community leads to lasting effects on host immune homeostasis, and is considered a major pathogenesis factor in multiple metabolic and immune disorders, including inflammatory bowel diseases, cancer, and intestinal infections. We are interested in characterizing the mechanisms by which individual members of the commensal microbiota modulate intestinal immune homeostasis. Specifically, we study how they control the balance between pro-inflammatory and anti-inflammatory T cells in the intestine. By learning the molecular 'tricks' that commensals use to manipulate host immunity we aim to develop strategies to target such cellular and molecular mechanisms to specifically, directionally and reversibly alter immune responses for the benefit of the human host. As an Innovation Fund investigator, Ivanov's lab is teaming with the lab of Pamela J. Bjorkman, Ph.D., to perform structural characterizations of the interactions between noninvasive microbes and intestinal cells. Findings from this research will allow Bjorkman and Ivanov to learn how bacteria interact with the intestine to modulate immune responses and identify mechanisms that help regulate normal bodily functions.