Research interests in this laboratory lie at the interface between chemistry and biology. Assembly line enzymes such as polyketide synthases have extraordinary potential for the programmable biosynthesis of complex natural products. Our laboratory seeks to understand the mechanistic logic of assembly line polyketide synthases, and to harness these insights in order to engineer new antibiotics. The prototypical system of interest to us is the 6-deoxyerythronolide B synthase, which synthesizes the macrocyclic core of erythromycin. Other examples of antibiotic biosynthetic pathways under investigation in our laboratory include the novel anti-infective agents A-74528 and guadinomine. Celiac disease is a T cell driven autoimmune disease of the small intestine that is induced by exposure to gluten from foodgrains such as wheat, rye and barley. Our laboratory seeks to understand the earliest molecular recognition and catalytic events in the pathogenic response of the celiac intestine to dietary gluten. We anticipate that such insights will pave the way for new therapies and biomarkers for this widespread but overlooked disorder. Our present efforts are directed at testing the hypothesis that transglutaminase 2, the principal autoantigen associated with celiac disease, is also a druggable target for therapeutic intervention.
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