Faculty

ROBERT H. TUKEY

• Professor of Pharmacology and Chemistry & Biochemistry
• Director, UCSD Superfund Basic Research Program

TEL: 858-822-0288
FAX: 858-822-0363
email: rtukey@ucsd.edu
website: http://superfund.ucsd.edu/

Key Words:  Carcinogenesis; Gene Regulation; Signal Transduction

Our laboratory has been interested in examining the role of xenobiotic receptors and the cellular events that regulate their function in controlling targeted gene expression. Postdoctoral fellows, graduate students and research staff work in one of two areas. The first involves the contribution of hazardous environmental toxicants in controlling gene expression and the events that lead to a toxic response using models of tissue culture as well as mice. Efforts are underway to examine the cellular signaling pathways that are involved in toxicant induced stress responses and the impact these responses have on cellular signaling mechanisms within defined cellular models. Work has evolved that is examining the role of these toxicants on dioxin receptor function, P450 regulation and cell specific directed apoptosis. The second major project is an examination and understanding of the cellular events involved in the control and regulation of the UDP-glucuronosyltransferase (UGT) genes in humans. Our efforts are directed toward characterizing those events that lead to the coordinated regulation of the UGT1 locus. Using approaches that include the characterization of UGT1 polymorphisms through functional analysis of the different UGT1A proteins and examination of the regulatory events that control UGT1A expression, we are understanding the role of these proteins in conventional patterns of drug metabolism but also as important regulators in preventing toxic or mutagenic episodes.

Selected Publications:

Chen, Y-H. and Tukey, R.H. Protein Kinase C modulates regulation of the CYP1A1 gene by the aryl hydrocarbon receptor. J. Biol. Chem. 271:26261-26266, 1996.

Strassburg, C.P. Manns, M.P. and Tukey, R.H. Differential down regulation of UDP-glucurono-sylansferase 1A locus is an early event in human liver and biliary cancer. Cancer Research. 57: 2979-2985, 1997.

Strassburg, C.P. Manns, M.P. and Tukey, R.H. Differential expression of the UGT1A locus in human liver, biliary, and gastric tissue: Identification of UGT1A7 and 1A10 transcripts in extrahepatic tissue. Molecular Pharmacology, 52:212-220. 1997.

Strassburg, C.P., Manns, M.P., and Tukey, R.H. Expression of the UDP-glucuronosyltransferase 1a locus in human colon: Identification and characterization if the novel extrahepatic UGT1A8. J.Biol.Chem. 273: 8719-8726, 1998.

Strassburg, C.P., Nguyen, N., Manns, M.P., and Tukey, R.H. UDP-glucuronosyltransferase Activity in Human Liver and Colon. Gastroenterology, 116: 149-160, 1999.