The proposed studies are focused on the epigenetic gene regulatory protein Mina and its physiological role in and molecular mechanisms for maintaining gut homeostasis and responding to infectious challenge. We propose 3 Aims to explore the cellular and molecular mechanisms of gut epithelial intrinsic regulation: (1) of the host response to infection with the whipworm parasite Trichuris muris;and (2) of commensal microbiota diversity.
This work will lay the foundation for the development of the next generation of biotherapeutics that will leverage knowledge of innate mechanisms of gut epithelial immunity. Our proposed studies focused on the epigenetic gene regulatory protein Mina will provide new insight into the physiological role of and molecular mechanisms for maintaining gut commensal diversity. This will illuminate how immune homeostasis is maintained by gut epithelial cells, faced with colonization by microbes ranging from parasites to commensals. In addition, this work will provide fundamental insight into innate gut epithelial mechanisms of protection from helminth infection, a major global problem. The Mina pathway impacts a number of other pathological conditions, including the development of pulmonary inflammation in a model of allergic asthma from which Mina KO mice are protected, intestinal adenocarcinoma (toward which Mina KO mice are predisposed) and multiple sclerosis modeled by the murine disease EAE (from which Mina KO mice are protected). Thus, the proposed studies are likely to provide basic insight into these additional areas where Mina's reach extends.
|Pillai, Meenu R; Lian, Shangli; Bix, Mark (2014) Mina: a Th2 response regulator meets TGF?. Curr Opin Immunol 31:38-43|