Stephen A. Weinman, M.D., Ph.D.

Professor
John Sealy Distinguished Chair for MD-PhD Studies

Affiliations: Department of Internal Medicine, Department of Neuroscience and Cell Biology

Phone: (409) 772-4286
Fax: (409) 772-5420
Email: sweinman@utmb.edu

Education

M.D., Ph.D., 1984, Washington University

Research Interests

Mitochondrial Dysfunction in Hepatitis C
Infection with the Hepatitis C Virus (HCV) causes a chronic liver disease characterized by slow but progressive liver injury leading to cirrhosis and hepatocellular carcinoma. Environmental and host factors such as alcohol consumption and increasing patient age greatly accelerate liver injury. A central problem in HCV research is how this occurs and whether this understanding can result in development of new therapeutic approaches. Our lab has discovered that the HCV core protein associates directly with mitochondria where it increases mitochondrial reactive oxygen species production, inhibits complex I mediated electron transport and sensitizes hepatocytes to the effects of alcohol and a number of apoptotic stimuli. Current areas of active research are characterizing the role of Endoplasmic Reticulum–Mitochondria interactions in the core effects, mitochondrial proteomic changes induced by HCV in mouse and human liver, and the potential of liver and mitochondrially directed antioxidants to prevent HCV induced liver injury.

Regulation of the Secretory and Endocytic Pathways by Intracellular Chloride Channels
Intracellular chloride channels are present in nearly all membrane enclosed compartments and control acidification and charge transfer across these barriers. Our lab has shown that several members of the family of voltage regulated chloride channels (ClC channels) play critical roles diverse events such as acidification of the endosome/lysosome compartment (ClC-3) and copper transport and incorporation into the liver derived cuproenzyme, ceruloplasmin (ClC-4). Current research is investigating the control of trafficking and intracellular sorting of ClC channels, and their participation in lysosomal, and iron and copper storage diseases.

Biographical Information

Postdoctoral, Digestive Diseases, Yale University

American Digestive Health Foundation Basic Science Research Award
American Gastroenterological Association Research Scholar

Selected Publications

Okuda, M.; Li, K.; Beard, M.R.; Showalter, L.A.; Scholle, F.; Lemon, S.M.; Weinman, S.A. Mitochondrial injury, oxidative stress and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology 122:366-375, 2002.

Li, X.; Wang, T.; Zhao, Z.; Weinman, S.A. The ClC-3 chloride channel promotes acidification of lysosomes in CHO-K1 and Huh-7 cells. Am. J. Physiol. Cell Physiol. 182:C1483-C1491, 2002.

Li, X.; Weinman, S.A. MRP-2 modulates the activity of chloride channels in isolated hepatocytes. Hepatology 36:65-71, 2002.

Li, X.; Weinman, S.A. Chloride channels and hepatocellular function: Prospects for molecular identification. Annu. Rev. Physiol. 64:13.1-13.25; 2002.

Weinman, S.A. and Kemmer N. Mechanisms of Bile Formation and Cholestasis, In Textbook of Gastroenterology, 4th Edition, T. Yamada, editor, Lippincott, Williams and Wilkins, Philadelphia, 366-388, 2003.

Morgan, T.R., Brenner, D., Everhart, J., French, S.W., Fried, M.W., Gretch, D.R., Koziel, M.J., McClain, C.J., Peters, M.G., Weinman, S.A., and Lucas, D.L. .Hepatitis C and alcohol: fundamental and translational research directions. Alcohol Clin Exp Res, 27: 726-731, 2003.

Wang, T.; Weinman, S.A. Involvement of chloride channels in hepatic copper metabolism: ClC-4 promotes formation of holoceruloplasmin. Gastroenterology. 126:1157-1168, 2004.

Showalter, L.A.; Weinman, S.A.; Osterlie, M.; Lockwood, S.F. Plasma appearance and tissue accumulation of non-esterified, free astaxanthin in C57BL/6 mice after oral dosing of a disodium disuccinate diester of astaxanthin. Comparative Biochemistry and Physiology 137:227-236, 2004.

Weinman, S.A. and Belalcazar, L.M. Hepatitis C: A Metabolic Liver Disease. Gastroenterology 126:917-919, 2004.

Otani, K.; Korenaga, M.; Beard, M.R.; Li, K.; Aman, K., Weinman, S.A. Showalter, L.A.,Wang, T., HCV core protein, CYP2E1 and alcohol produce mitochondrial injury and cytotoxicity in hepatoma cells. Gastroenterology, 128:96-107; 2005.