Primary general research interests are focused on the molecular mechanisms controlling cell-specific expression of individual cytochrome P450 (CYP450) isozymes, and the concomitant effects of xenobiotics on the balance between detoxification and bioactivation pathways for drugs, carcinogens and other chemicals. The laboratory also maintains a secondary interest in the molecular mechanisms of CYP450-mediated bioactivation reactions, especially with respect to molecular mechanisms of chemical carcinogenesis.

Current research projects are focused on: a) Identification and characterization of endogenous signaling pathways, especially those whereby endogenous ligands for receptors are also substrates for human cytochromes P450 and perturbations of these endogenous signaling pathways results in altered cellular growth, differentiation or homeostasisa) b) elucidation of molecular mechanisms by which xenobiotics regulate expression of the CYP450 and GST gene families and alter RNA splicing; c) the structure, function and regulation of CYP1B1, P450c1 and CYP26 of the vitamin D and retinoic acid synthetic pathways, respectively; d) identification of naturally occurring and endogenous P450 substrates with gene regulatory functions (PXR – Pregnane X Receptor) and (AhR – Aryl Hydrocarbon Receptor). New projects currently under development will investigate the molecular mechanisms of prostate carcinogenesis.

Education

• University of Wisconsin-Madison, B.S. Biochemistry, 1975

• University of Wisconsin-Madison, M.S. Toxicology, 1978

• University of Wisconsin-Madison, Ph.D. Toxicology, 1981

Honors

• NIEHS National Research Service Award Postdoctoral Trainee

• Institute for Comparative and Environmental Toxicology, Cornell University, 1981 - 1983

• NIEHS National Research Service Award Postdoctoral Trainee

• University of Wisconsin Center for Environmental Toxicology, University of Wisconsin-Madison, 1983 - 1984

• NIH Toxicology/ALTX1 Study Section - (1997- 00)

Selected Publications

Marcus, C., Wilson, N., Jefcoate, C., Wilkinson, C., and Omiecinski, C. (1990) Selective induction of cytochrome P-450 isozymes in rat liver by 4-n-alkylmethylenedioxybenzenes. Arch. Biochem. Biophys. 277:8-16

Updyke, L.W., Yoon, H.A., Kiorpes, A.L., Robinson, J.P., Pfeifer, R.W. and Marcus, C.B. (1991) 3-methylindole (3MI)-induced splenotoxicity: I. Biochemical mechanisms of cytotoxicity. Toxicol. Appl. Pharmacol. 109:375-390

Otto, S., Marcus, C., Pidgeon, C. and Jefcoate, C.R. (1991). A novel drenocorticotrophin-inducible cytochrome P450 from rat adrenal microsomes catalyzes polycyclic aromatic hydrocarbon metabolism. Endocrinology 129(2):970-982

Eberhart, J., Coffing, S.L., Anderson, J.N., Marcus, C., Baird, W.M., Park, S.S. and Gelboin, H.V. (1992) The time-dependent increase in the binding of benzo[a]pyrene to DNA through (+)-anti-benzo[a]pyrene-7-8-diol-epoxide in primary rat hepatocyte cultures results from induction of cytochrome P450IA1 by benzo[a]pyrene treatment. Carcinogenesis 13(2):297- 301

Yoon, H. A, Marcus, C.B. and Pfeifer, R.W. (1993) Induction of superoxide by 12-O-tetradecanoylphorbol-13-acetate and thapsigargin, a non-phorbol ester-type tumor promoter, in peritoneal macrophages elicited from SENCAR and B6C3F1 mice: A permissive role for the arachidonic acid cascade in signal transduction. Mol. Carcinogenesis. 7:116-125

Greenlee, W.F., Sutter, T.R. and Marcus, C. (1994) Molecular basis of dioxin actions on rodent and human target tissues. IN: Receptor-Mediated Biological Processes: Implications for evaluating carcinogenesis. Spitzer, H., Slaga, T., Greenlee, W. and McClain, M., eds. Progress in Clinical and Biological Research. vol. 387, pp. 47-58.

Wiley-Liss, NY. Polzer, R., Coffing, S., Marcus, C., Park, S., Gelboin, H.V. and Baird, W. (1995) Inhibition of benzo[a]pyrene metabolism by insulin, FITC-insulin and an FITC insulin-antibody conjugate in the human hepatoma cell line HepG2. Chem-Biol. Interact. 97:307-318

McKay, J.A., Melvin, W.T., Ah-See, A.K., Ewen, S.W.B., Greenlee, W.F., Marcus, C.B., Burke, M.D. and Murray, G.I. (1995) Frequent expression of cytochrome P4501B1 in breast cancer. FEBS Letters 374:270-272

Einolf, H, Story, W. Marcus, C. W. Larsen, M, Jefcoate, C., Greenlee, W. Yagi, H., Jerina, D. Amin. S., Park, S., Gelboin, H. and Baird, W. (In Press) The role of P450 enzyme induction in the metabolic activation of benzo[c]phenanthrene in human cell lines and mouse epidermis. Chem. Res. Toxicol.

Scharf, M.E., Neal. J.J., Marcus, C. and Bennett, G.W. (submitted) Cytochrome P450 purification and immunological detection in an insecticide resistant strain of german cockroach (Blattella germanica, L.) Insect Biochem. Mol. Bio.

Sidhu, J.S. Marcus, C., Parkinson, A., and Omiecinski, C.J. (1998) Differential Induction of Cytochrome P450 Gene Expression by 4-n-Alkyl-methylenedioxybenzenes in primary rat hepatocyte cultures. J. Biochem. Toxicol. 12(5):253-262

Sharpe, J. F., Eaton, D. L. and Marcus, C. B. (2001) Digital Toxicology Education Tools: Education, Training, Case Studies, and Tutorials. Toxicology 157(1-2):141-152.

Rat Cytochrome P450c24 (CYP24A1) and the Role of F249 in Substrate Binding and Catalytic Activity. (2004) Andrew Annalora, Ekaterina Bobrovnikova-Marjon, Rita Serda, Letitia Lansing, Mark L. Chiu, Andrzej Pastuszyn, Srinivas Iyer, Craig B. Marcus, and John L. Omdahl (in press)

Chiaro, C.R., Marcus, C. and Perdew, G. H. The characterization of a Putative High Affinity Endogenous Ah Receptor Ligand from CV-1 Cells. (in preparation)