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• PUBLICATIONS (last 3-5 years):

O'Rourke, M.F., Tuma, D.J., and Casey, C.A. Decreased binding and autophosphorylation of the EGF-receptor in ethanol-fed rats. Biochemical Pharmacology 53, 1445-1450, 1997

Tworek, B.L., Oka, J.A., Casey, C.A., and Weigel, P.H. Ethanol feeding causesinactivation of both State 1 and State 2 rat hepatic asialoglycoprotein receptors. Alcohol. Clin. and Exp. Res., 21, 1429-1434, 1997

Tuma, D.J., Todero, S.L., Barak-Bernhagen, M., Casey, C.A., and Sorrell, M.F.Chronic ethanol ingestion impairs TGF -stimulated receptor autophosphorylation. ALCOHOL, 15:233-238, 1998

Tworek, B.L., Wiegert, R.L., Tuma, D.J., and Casey, C.A. Effects of monensinon ethanol-induced alterations in function of hepatocellular asialoglycoprotein receptor subpopulations. Alcohol. Clin. and Exp. Res. . 22:97-104, 1998

Tworek, B.L., Wiegert, R.L., Jeanette, J.P., Tuma, D.J., and Casey, C.A.Differential effects of monensin on asialoglycoprotein receptor function after short-term ethanol administration. Biochemical Pharmacology, 55:1603-1609, 1998

Clemens, D.L., Casey, C.A., Sorrell, M.F., and Tuma, D. J. Ethanol oxidation mediates impaired hepatic receptor-mediated endocytosis. Alcoholism: Clinical and Experimental Research, 22:778-779, 1998

McVicker, B.L. and Casey, C.A. Effects of ethanol on receptor-mediatedendocytosis in the liver, ALCOHOL 19: 255-260, 1999

McVicker, B.L. and Casey, C.A. Ethanol-impaired hepatic protein trafficking:Concepts from the asialoglycoprotein receptor system. Clinical Biochemistry, 32:557-561, 1999

McVicker, B.L., Tuma, D.J., and Casey, C.A. Ethanol administration results in hyperphosphorylation of the asialoglycoprotein receptor in isolated rat hepatocytes. Biochemical Pharmacology, 60: 343-351, 2000.

Casey, CA, Nanji, A. A., Cederbaum, A.I., Adachi, M., and Takahashi, T.  Alcoholic Liver Disease and Apoptosis. Alcohol Clin and Exp Res,Vol 25 No. 5: 49S-53S, 2001.

Nagy, LE, Lakshman MR, Casey, CA and Bearer, CF.  Ethanol and Membrane Protein Trafficking:  Diverse Mechanism of Ethanol action.  Submitted:  Alcohol: Clin and Exp. Res. 2001

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• PREVIOUS GRADUATE STUDENTS/POST-DOCTORAL FELLOWS (present location):

Graduate student: Benita Tworek (McVicker). Obtained her Ph.D. in 1997; currently an instructor in the Department of Internal Medicine, Section of GI.
Post Doctoral students: Marie O’Rourke, Ph.D. 1993-1996. Currently on the faculty of the science department at the College of Saint Mary in Omaha, NE.

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• CURRENT RESEARCH PROJECTS:

Ethanol abuse is a major health problem in the United States, although the mechanism by which ethanol exhibits the hepatotoxic effects is presently unknown. Results from our laboratory in recent years have shown the ethanol administration markedly impairs the hepatic process of receptor-mediated endocytosis (RME). We have used the specific asialoglycoprotein receptor (ASGP-R) as a model and have identified multiple steps of RME (binding, internalization, degradation, receptor recycling and receptor-ligand dissociation) that are impaired by ethanol treatment. These defects are most prominent in the centrilobular region of the liver, the area where alcoholic liver injury starts and predominates, and occur after an early as one week of ethanol feeding. Recent evidence from other laboratories shows a role for the ASGP-R in clearing apoptotic bodies produced during programmed cell death (apoptosis). The finding that the ASGP-R is involved in removal of cells undergoing apoptotic indicates a new perspective in the understanding of a physiological role for this receptor. We hypothesize that one of the functional consequences of ethanol-induced impairments in ASGP-R function is a decreased clearance of apoptotic bodies produced in the liver and that an accumulation of these bodies could be deleterious. We currently have obtained evidence showing that hepatocytes from ethanol-fed animals are more susceptible to become apoptotic than their pair-fed control counterparts and that these chances are exacerbated when endocytosis by the ASGP-R. is blocked. We are investigating these phenomena further by examining uptake of labeled apoptotic cells by healthy hepatocytes to determine if uptake is likewise impaired after ethanol feeding. Alterations in clearance of cells by the ASGP-R could contribute to the pathologic changes that occur during alcohol liver injury.

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• SPECIALIZED LABORATORY/CLINICAL RESEARCH RESOURCES:

Confocal microscope, FACs analysis