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Research | Core Facilities | Patient Studies | Tech Transfer | Seminars | Intranet | Jobs | Search | Contact Us | Ways To Give HOME |
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More about Cardiovascular Biology Research Program
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Research Interests Many membrane and secreted proteins are modified by O-glycans. The main O-glycan forms are core 1– and core 3–derived structures that are expressed primarily in endothelial, epithelial, and hematopoietic cells. Biosynthesis of core 1– and core 3–derived O-glycans is controlled, respectively, by the core 1 1,3-galactosyltransferase (T-synthase) and core 3 1,4-N-acetylglucosaminyltransferase (C3GnT). To investigate O-glycan functions, we generated mice with global, tissue-specific, or inducible deficiencies in T-synthase and/or C3GnT. Our main goals are to: a) investigate biological functions of protein O-glycosylation in endothelial cells, epithelial cells, and hematopoietic cells, and b) determine mechanisms by which O-glycans regulate vascular development, inflammation, and tumorigenesis. Current focuses are primarily on O-glycans in lymphangiogenesis and intestinal disease, two areas developed in my lab with high human disease relevance. We demonstrated that endothelial O-glycans regulate the O-glycoprotein podoplanin to control the separation of blood and lymphatic systems during embryonic and postnatal development. We are determining how podoplanin regulates lymphangiogenesis. Intestinal O-glycan expression is frequently altered in patients with colitis and colorectal tumors, which plays an unknown etiological role. We found that mice lacking intestinal O-glycans have impaired intestinal mucus barrier function and develop spontaneous colitis and colorectal tumors, supporting a causal role for abnormal O-glycans in the pathogenesis of these intestinal diseases. We are investigating mechanisms underlying this pathology. Many tumors metastasize via lymphatics in the absence of functional intratumor lymphatics. We will use mouse tumor models, including our colorectal tumor mouse model, to test the role of aberrant lymphangiogenesis in tumor metastasis. This direction synergizes our strengths in lymphangiogenesis and intestinal disease. Integrating data from these studies will provide a broad view of O-glycosylation function in health and disease. Joined OMRF Scientific Staff in 2002. Mailing Address
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