Dr. Ashutosh Mangalam received a four-year VA Merit Award entitled “Role of HLA Class-II Polymorphism in the Regulation of Host-Microbiota Symbiosis”. HLA class-II genes and gut microbiota have emerged as important genetic and environmental factors linked with the pathobiology of multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system that affects around one million people in the US. The proposed studies will build upon recent findings from Dr. Mangalam’s laboratory showing that patients with MS have gut dysbiosis (altered gut microbiome compared to healthy controls) and HLA class-II polymorphisms can regulate gut microbiota composition. This study will test the hypothesis that HLA class-II molecules modulate host immunity through regulation of the host microbiome during early life and adulthood, and perturbation of the microbiome may lead to predisposition/exacerbation of inflammatory diseases such as MS. Specifically, the study will utilize novel transgenic mice expressing MS-linked HLA-class-II genes to determine the mechanism(s) through which interactions between genes (HLA class-II) and environmental factors (microbiota) might predispose to or protect from MS. The research will be conducted in collaboration with Dr. Kevin Legge within the Department of Pathology. The focus of Dr. Mangalam’s team is to understand the role of the gut microbiome in MS with a long-term goal of manipulating the gut microbiome as a treatment option for MS patients.