My field of interest is focused on mechanisms of innate immunity in the gastrointestinal tract that promote protective responses against pathogens, while preventing unwanted inflammatory responses to our resident microbiota. Specifically, my research centers on the intestinal mucus system, a network of glycoproteins manufactured and secreted by goblet cells, and how defects in this system contribute to susceptibility to infections, inflammatory bowel disease (IBD), and colon cancer. To study this, I employ a repertoire of specialized skills to probe host-microbiota interactions in disease causation at the organismal, tissue, cellular and molecular level, including functional analysis of mucins and glycan biology, gut ecology; and state-of-the-art imaging and genetic modeling. Using these approaches (during my postdoctoral training at Oklahoma Medical Research Foundation) has led to novel insights into how the intestine utilizes two key glycosyltransferases, Core-1 β1,3 galatactosyltransferase (Core 1 synthase) and Core 3 β1,3N-acteylglucosaminyltransferase (Core 3 synthase), which decorate mucin proteins with sugars (aka glycans), to promote optimal mucus function that keeps the microbiota at a “healthy distance” from the gut, and prevent spontaneous IBD, as well as cancers of the colon and small intestine. My independent studies build directly on this work, where I am addressing how the expression and activity of Core 1- and 3- synthases are controlled in humans and preclinical murine model systems; how mucin-type O-glycans impact the structure and function of microbial communities in the gut, and how O-glycans regulate formation and function of the intestinal mucus system. The goals of this work aim to increase our knowledge of the fundamental roles of mucins and their O-glycans in the gut, and devise novel methods of intervention to boost their protective capacities in IBD and cancer patients where defects in these systems are thought to contribute to pathogenesis.
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