The focus of my laboratory is to understand regulatory mechanisms during infection and autoimmunity at mucosal sites, particularly within the gastrointestinal tract. The adult human intestine alone contains up to 100 trillion micro-organisms─and no other tissue is submitted to a greater level of antigenic pressure than the gut, which is constantly exposed to food and environmental antigens and the threat of invasion by pathogens. At birth, for example, the human gastrointestinal tract undergoes a massive exposure to these antigens, and throughout the average human life there are multiple instances of the remodeling of the gut flora following infection. All these occurrences impose a unique challenge to the gastrointestinal environment. In response, to maintain immune homeostasis, the intestinal immune system has evolved redundant regulatory strategies. Several subsets of immune cells with immune modulatory function reside within the gastrointestinal tract. Specifically, we study Foxp3 expressing regulatory T cells (Tregs), which play a central role in controlling intestinal homeostasis.

Recent studies have demonstrated that the ability of Tregs to control defined polarized settings requires plasticity, the acquisition of characteristics specific to the glycoprotein CD4+ T effector subsets. Such adaptation comes with an inherent cost, however; as my research team and other researchers have demonstrated, in extreme instances of inflammation such adaptation can actually be associated with the expression of pro-inflammatory effector cytokines (i.e., interferon gamma and interleukin 17A). We recently identified GATA3, the canonical Th2 transcription factor, as a critical regulator of Treg adaptation during inflammation in tissues. Our goal is to understand how GATA3 regulates this and to identify other factors involved in Treg adaptation during inflammation. Our laboratory employs natural enteric parasitic infections of mice and the T cell dependent model of colitis to decipher both the environmental cues and cell- intrinsic requirements for Treg cell plasticity, stability and function at mucosal sites. The ultimate goal of our research is to clarify the pathogenesis of inflammatory bowel disease (IBD) and develop novel treatment modalities for patients.