Gregory C. Sephel, Ph.D.
Dept of Pathology, Microbiology and Immunology
Clinical Pathology Director VA
VA TN Valley Healthcare System
Phone: 615-327-5345 or 615-327-4751 ext. 6037
Campus Mail address:
Pathology, Microbiology, and Immunology - 3rd Fl
C-3321 MCN (2561)
US Mailing address:
Vanderbilt University School of Medicine
Pathology, Microbiology and Immunology
C-3321 MCN (2561)
Nashville, TN 37232-2561
The role of basement membrane and extracellular matrix components,
structures and cells in vascular biology, wound healing and cancer
My research laboratory is not currently active, however, in addition to my clinical interests, I maintain strong teaching and academic interests in factors that control morphogenesis, healing and vessel formation in wounds and tumors.
The extracellular matrix (ECM) forms the environment in which all cells reside, including circulating cells, which develop and function in matrix. ECM has been shown to be a dynamic molecular meshwork which directs cell migration during development and repair, acts as a determinant of cell organization during organ formation, and affects cell shape, differentiation and expression. It also translates, transforms, stores, and delivers information to cells from endogenous growth factors and cytokines, forms a barrier to metastasis, and composes a metabolic history of the cell. I continue to have a passionate interest in basement membranes (BM), which form the interface between different tissue components important in morphogenesis and organ function. The BM is composed of specialized matrix molecules such as collagen (type IV), laminin and a large polyanionic heparin containing proteoglycan that are spcecific to tissue and stage of development. These molecules self-assemble in defined ratios such that networks of glycoproteins with proteoglycans cover a lattice of type IV collagen. The ingredients for capillary netowrk formation are endothelial cells growth factors and extracellular matrix, particularly BM components. We identified an in vivo model which enables the study of capillary specific regulation of basement membrane components during angiogenesis without interference from endogenous tissue basement membrane. Using this model, we characterized the temporal appearance and the collagen IV and laminin chain composition in nascent capillary basement membranes and compared processes of capillary morphogenesis with changes in BM gene expression.
Interests in inflammation and morphogenesis led us to study the complementary interaction between granulation tissue fibroblasts and endothelial cells in controlling the type of matrix that is synthesized when new blood vessels grow into the provisional matrix wound tissue. We demonstrated that prostaglandins influcence collagen accumulation and growth factor expression, which in turn affect BM production and lumen formation in endothelial cells. Additional studies demonstrated the affects of in vivo hyperglycemia on basement membrane expression during capillary mophogenesis.