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Dr. Xia:

Dr. Xia's CV in brief

Publications

Cardiovascular Biology Research Program

Lijun Xia, M.D., Ph.D. Assistant Member, Cardiovascular Biology Research Program Adjunct Assistant Professor, Department of Biochemistry and Molecular Biology,   University of Oklahoma Health Sciences Center

Research Interests
O-glycosylation is a common posttranslational modification on many membrane and secreted proteins, but the functions of O-glycans are largely unexplored. My laboratory studies O-glycosylation function in physiologic and pathologic processes. Our experiments employ conventional and conditional targeted gene deletions to produce mice with global or tissue-specific or inducible deficiencies in glycosyltransferase enzymes controlling key pathways of O-glycosylation. O-glycans have two main subtypes referred to as core 1- and core 3-derived O-glycans. Core 1-derived O-glycans are mainly expressed in endothelial and epithelial cells, while the expression of core 3-derived O-glycans is largely restricted to intestinal epithelium. Our current focus is on the functions of O-glycans in vascular endothelial cells and intestinal epithelial cells.

Our interest in endothelial cells developed from our previous studies of mice with global deficiency of  T-synthase (T-syn^-/-), a critical glycosyltransferase for biosynthesis of core 1-derived 2 O-glycans. The T-syn^-/- mice developed unexpected abnormal angiogenesis with brain hemorrhage that was fatal at embryonic day 14. To identify whether O-glycans in endothelial cells are required for angiogenesis, we have developed mice lacking T-synthase specifically in endothelial cells or in perivascular tissues. We are breeding transgenic mice expressing T-synthase specifically in endothelial cells with T-syn^-/- mice to determine whether endo-thelial-cell expression of T-synthase will rescue defective angiogenesis. We have also developed endothelial cell lines derived from T-syn^-/- mice to explore the potential mechanisms for O-glycan-dependent angiogenesis.

Both core 1- and core 3-derived O-glycans are found in gastrointestinal tracts, which constitute the major structural components of intestinal mucus. To study the role of core 1-derived O-glycans in these tissues, we developed intestinal epithelial cell-specific T-synthase-deficient mice (Epi T-syn^-/-). To investigate the role of core 3-derived O-glycans, we developed mice with deficiency of core 3 b1,4-N-acetylglucosaminyltransferase (C3GnT^-/-), an enzyme controlling the synthesis of core 3-derived O-glycans. We have also generated mice lacking both core 1- and core 3-derived O-glycans by breeding the Epi T-syn^-/- and C3GnT ^-/- mice. These mouse models develop significant defects in intestinal function. We are now characterizing the phenotypes of these mouse models and delineating the mechanisms that underlie the phenotypes.

Joined OMRF Scientific Staff in 2002.

Mailing Address
Cardiovascular Biology Research Program, MS 45
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, Oklahoma 73104

Contact Information
Phone: (405) 271-7892
Lab: (405) 271-3979
Fax: (405) 271-3137
E-mail: Lijun-Xia@omrf.org