Gregory C. Sephel, Ph.D.

Associate Professor

gregory.c.sephel@vanderbilt.edu
Faculty Appointments
Associate Professor of Pathology, Microbiology and Immunology
Education
Ph.D., Cell Biology & Immunology, University of Utah, Salt Lake City, UtahB.S., Biological Sciences, University of California, Irvine, California
Office Address
Pathology and Lab Medicine (113)
VA TN Valley Healthcare System - Nashville Campus
1310 24th Ave.
Nashville, TN 37212-2637
Research Description
My research laboratory is no longer active, however, in addition to my clinical interests, I maintain strong teaching and academic interests in factors that control inflammation, morphogenesis, healing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.
Clinical Description
I have a broad and deep interest in the study and discipline of Clinical Pathology. Pathology is a hub of medicine and interacts with nearly all medical disciplines, which satisfies the interests of a generalist with an investigative spirit. Specific laboratory interests and responsibilities are in Clinical Chemistry, Toxicology, Therapeutic Drugs, Immunochemistry, Endocrinology, Protein Electrophoresis, Hemoglobin Identification, Coagulation, Viral Markers, Point-of-Care Testing, Processing, Reference Testing and General Laboratory. Functions include test design and selection, workflow, quality control, interpretation, consultation, and problem solving. Early training included business classes which provided helpful background to the business side to Pathology which includes management of a 24/7 diverse operation, cost accounting and industrial engineering. My duties within a large health network have given me a varied experience in systems structure and laboratory benchmarking.
Research Keywords
Cell and molecular biology of inflammation processes, basement membrane, collagens, matrix glycoproteins, elastin, proteoglycans along, integrins, metalloproteinases, ADAMs, TIMPs, and growth factors in vascular biology, wound healing, angiogenesis, morphogenesis and cancer.
Publications
Sephel Gregory, et al. A critically low carbon dioxide in patients with severe hypertriglyceridemia. J App Lab Med. 2017; 2(1): 123-5.

Rubin's Pathology Clinicopathologic Foundation of Medicine 7th Ed. 7th. [place unknown]: Wolters Kluwer; 2015.

Sephel Gregory, Laposata Michael, et al. Transiently increased variation between a point-of-care and laboratory INR method after a long period of correlation. Am J Clin Path. 2013; 140: 475-86.

Rubin's Pathology Clinicopathologic Foundation of Medicine 6th Ed. [place unknown]: Wolters Kluwer; 2012.

Sephel GC and Woodward SC. Rubin's Pathology 5th ed. [place unknown: publisher unknown]; 2007.

Sephel GC and Woodward SC. Rubin's Pathology 4th ed. [place unknown: publisher unknown]; 2004.

Prokop A, Kozlov E, Nun Non S, Dikov MM, Sephel GC, Whitsitt JS, Davidson JM. 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. 2001; 3(2): 245-61. PMID: 11478332, ISSN: 1520-9156.

Hb Inkster[a85(F6)Asp-Val] Found in a Caucasioan Male with polycythemia. Hemoglobin. 2000; 4((24)): 333-9.

Sephel GC, Kennedy R, Kudravi S. Expression of capillary basement membrane components during sequential phases of wound angiogenesis. Matrix Biol. 1996 Sep; 15(4): 263-79. PMID: 8892226, PII: S0945-053X(96)90117-1, ISSN: 0945-053X.

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. 1993 Oct; 25(10): 67-9. PMID: 10171728, ISSN: 0580-7247.

Smith MC, Sephel GC, Woodward SC. Spreadsheet templates for calculating linearity according to EP6-P. MLO Med Lab Obs. 1992 Nov; 24(11): 59-60, 62. PMID: 10122447, ISSN: 0580-7247.

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

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. 1991 Nov 11/1/1991; 290(2): 320-5. PMID: 1834017, ISSN: 0003-9861.

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. 1991 Mar; 146(3): 451-9. PMID: 2022699, DOI: 10.1002/jcp.1041460316, ISSN: 0021-9541.

Smith MC, Sephel GC. Long-term in vitro stability of cyclosporine in whole-blood samples. Clin. Chem. 1990 Nov; 36(11): 1991-2. PMID: 2242587, ISSN: 0009-9147.

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. 1990; 580: 302-10. PMID: 2186693, ISSN: 0077-8923.

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. Elastin Chemical and Biological Aspects (Springer Verlag; Eds Tamburro, Davidson). [place unknown: publisher unknown]; 1990.

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. 1989 Sep 9/25/1989; 264(27): 16174-82. PMID: 2777785, ISSN: 0021-9258.

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. 1989 Sep; 135(1): 172-81. PMID: 2504632, ISSN: 0012-1606.

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. 1989 Jul 7/31/1989; 162(2): 821-9. PMID: 2757641, PII: 0006-291X(89)92384-X, ISSN: 0006-291X.

Sephel GC, Byers PH, Holbrook KA, Davidson JM. Heterogeneity of elastin expression in cutis laxa fibroblast strains. J. Invest. Dermatol. 1989 Jul; 93(1): 147-53. PMID: 2745999, ISSN: 0022-202X.

Sephel GC, Burrous BA, Kleinman HK. Laminin neural activity and binding proteins. Dev. Neurosci. 1989; 11(4-5): 313-31. PMID: 2676457, ISSN: 0378-5866.

Sephel GC, Sturrock A, Giro MG, Davidson JM. Increased elastin production by progeria skin fibroblasts is controlled by the steady-state levels of elastin mRNA. J. Invest. Dermatol. 1988 May; 90(5): 643-7. PMID: 3361140, ISSN: 0022-202X.

Kleinman HK, Luckenbill-Edds L, Cannon FW, Sephel GC. Use of extracellular matrix components for cell culture. Anal. Biochem. 1987 Oct; 166(1): 1-13. PMID: 3314585, PII: 0003-2697(87)90538-0, ISSN: 0003-2697.

Sephel GC, Buckley A, Davidson JM. Developmental initiation of elastin gene expression by human fetal skin fibroblasts. J. Invest. Dermatol. 1987 Jun; 88(6): 732-5. PMID: 3585057, ISSN: 0022-202X.

Davidson JM, Sephel GC. Regulation of elastin synthesis in organ and cell culture. Meth. Enzymol. 1987; 144: 214-32. PMID: 3626872, PII: 0076-6879(87)44180-3, ISSN: 0076-6879.

Sephel GC, Davidson JM. Elastin production in human skin fibroblast cultures and its decline with age. J. Invest. Dermatol. 1986 Mar; 86(3): 279-85. PMID: 3745952, ISSN: 0022-202X.

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. 1985 Feb; 75(2): 672-8. PMID: 3973023, PMCID: PMC423554, DOI: 10.1172/JCI111746, ISSN: 0021-9738.

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