.

Department of Pathology, Microbiology, and Immunology

 

 

  Gregory C. Sephel, Ph.D.

 

 

  Associate Professor

  Dept of Pathology, Microbiology and Immunology

  Clinical Pathology Director VA

 

 

  Contact Information


 

Office Location:

A-09

VA TN Valley Healthcare System
   Phone: 615-327-5345 or 615-327-4751 ext. 6037  

E-mail: gregory.sephel@va.gov; gregory.sephel@vanderbilt.edu

 

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

 

 

  Research Specialty

 

 

  The role of basement membrane and extracellular matrix components,

  structures and cells in vascular biology, wound healing and cancer

 

 

  Research Description

 

 

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.

 

 

 

Education

 

 

Ph.D., University of Utah, SLC, UT
MT (ASCP), Mercy Hospital, San Diego, CA
B.S., University of California, Irvine, Irvine CA

 

 

Research Keywords

 

 

extracellular matrix basement membrane angiogenesis morphology clinical biochemistry and physiology toxicology endocrinology

 

 

Research Description

 

 

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.

 

 

Publications

 

 

Sephel GC, Kennedy R. Unique basement membrane composition and collagen IV processing in an embryo derived rat parietal yolk sac cell line (Pending).

Sephel GC and Woodward SC. Repair, Regeneration, Fibrosis. Rubin's Pathology 5th ed, 71-98, 2007

Sephel GC and Woodward SC. Repair, Regeneration, Fibrosis. Rubin's Pathology 4th ed, 85-116, 2004

Prokop, A, Kozlov, E, Nun Non, S, Dikov, M M, Sephel, G C, Whitsitt, J S, Davidson, J M. Towards retrievable vascularized bioartificial pancreas: induction and long-lasting stability of polymeric mesh implant vascularized with the help of acidic and basic fibroblast growth factors and hydrogel coating. Diabetes Technol Ther, 3(2), 245-61, 2001

Aguinaga, MD, Sephel GC, Kutlar EA, Turner EA, Park, D ex post facto. Hb Inkster[a85(F6)Asp-Val] Found in a Caucasioan Male with polycythemia. Hemoglobin, 4(24), 333-339, 2000

Sephel, GC, Kennedy, R, Kudravi, S. Expression of capillary basement membrane components during sequential phases of wound angiogenesis. Matrix Biol, 15(4), 263-79, 1996

Smith, MC, Sephel, GC, Woodward, SC. Spreadsheet templates for calculating precision according to NCCLS (National Committee for Clinical Laboratory Standards) guidelines. MLO Med Lab Obs, 25(10), 67-9, 1993

Smith MC, Sephel GC, Woodward SC, Duncan DJ. Templates for generating Levy-Jenning and Westgard QC charts. Medical Laboratory Observer, 12(24), 55-61, 1992

Smith, MC, Sephel, GC, Woodward, SC. Spreadsheet templates for calculating linearity according to EP6-P. MLO Med Lab Obs, 24(11), 59-60, 62, 1992

Kleinman, HK, Weeks, BS, Cannon, FB, Sweeney, TM, Sephel, GC, Clement, B, Zain, M, Olson, MO, Jucker, M, Burrous, BA. Identification of a 110-kDa nonintegrin cell surface laminin-binding protein which recognizes an A chain neurite-promoting peptide. Arch Biochem Biophys, 290(2), 320-5, 1991

Tashiro, K, Sephel, GC, Greatorex, D, Sasaki, M, Shirashi, N, Martin, GR, Kleinman, HK, Yamada, Y. The RGD containing site of the mouse laminin A chain is active for cell attachment, spreading, migration and neurite outgrowth. J Cell Physiol, 146(3), 451-9, 1991

Smith, MC, Sephel, GC. Long-term in vitro stability of cyclosporine in whole-blood samples. Clin Chem, 36(11), 1991-2, 1990

Davidson JM, Giro MG, Sutcliffe M, Zoia O, Quaglino D Jr, Liu J-M, Perkett B, Meyrick B, Broadley KN, Russell S and Sephel GC. Regulation of Elastin Synthesis. Elastin Chemical and Biological Aspects (Springer Verlag; Eds Tamburro, Davidson), 395-405, 1990

Kleinman, HK, Sephel, GC, Tashiro, K, Weeks, BS, Burrous, BA, Adler, SH, Yamada, Y, Martin, GR. Laminin in neuronal development. Ann N Y Acad Sci, 580, 302-10, 1990

Sephel, GC, Burrous, BA, Kleinman, HK. Laminin neural activity and binding proteins. Dev Neurosci, 11(4-5), 313-31, 1989

Sephel, GC, Byers, PH, Holbrook, KA, Davidson, JM. Heterogeneity of elastin expression in cutis laxa fibroblast strains. J Invest Dermatol, 93(1), 147-53, 1989

Sephel, GC, Tashiro, KI, Sasaki, M, Greatorex, D, Martin, GR, Yamada, Y, Kleinman, HK. Laminin A chain synthetic peptide which supports neurite outgrowth. Biochem Biophys Res Commun, 162(2), 821-9, 1989

Sephel, GC, Tashiro, K, Sasaki, M, Kandel, S, Yamada, Y, Kleinman, HK. A laminin-pepsin fragment with cell attachment and neurite outgrowth activity at distinct sites. Dev Biol, 135(1), 172-81, 1989

Tashiro, K, Sephel, GC, Weeks, B, Sasaki, M, Martin, GR, Kleinman, HK, Yamada, Y. A synthetic peptide containing the IKVAV sequence from the A chain of laminin mediates cell attachment, migration, and neurite outgrowth. J Biol Chem, 264(27), 16174-82, 1989

Sephel, G C, Sturrock, A, Giro, M G, Davidson, J M. Increased elastin production by progeria skin fibroblasts is controlled by the steady-state levels of elastin mRNA. J Invest Dermatol, 90(5), 643-7, 1988

Sephel, GC, Buckley, A, Davidson, JM. Developmental initiation of elastin gene expression by human fetal skin fibroblasts. J Invest Dermatol, 88(6), 732-5, 1987

Kleinman, HK, Luckenbill-Edds, L, Cannon, FW, Sephel, GC. Use of extracellular matrix components for cell culture. Anal Biochem, 166(1), 1-13, 1987

Davidson, JM, Sephel, GC. Regulation of elastin synthesis in organ and cell culture. Methods Enzymol, 144, 214-32, 1987

Sephel, GC, Davidson, JM. Elastin production in human skin fibroblast cultures and its decline with age. J Invest Dermatol, 86(3), 279-85, 1986

Giro, MG, Oikarinen, AI, Oikarinen, H, Sephel, G, Uitto, J, Davidson, JM. Demonstration of elastin gene expression in human skin fibroblast cultures and reduced tropoelastin production by cells from a patient with atrophoderma. J Clin Invest, 75(2), 672-8, 1985