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Molecular Genetics and Genomics Program at Wake Forest University School of Medicine

Charles Morrow

Associate Professor of Biochemistry 

A.B., 1974 Cornell University, Ithaca, NY 
Ph.D., 1980 (Biochemistry) St. Louis University, St. Louis, MO 
M.D., 1983 University of Missouri - Columbia, MO 

 

The emergence of antineoplastic drug resistance constitutes a major problem in the successful treatment of disseminated cancer. Frequently, in both clinical and experimental systems of anticancer drug treatment, exposure to one anticancer drug results in the development of cancer cells that are resistant to multiple drugs in addition to the selecting drug used in treatment. This phenomenon is termed multidrug resistance (MDR) and is associated with the increased expression of a number of genes believed to contribute to the MDR phenotype.

A major focus of my research concerns the role of combined actions of glutathione transferases (GST) and the multidrug resistance protein (MRP) family efflux transporters in the emergence of anticancer drug resistance and carcinogen detoxification. I am investigating the interplay between the drug/toxin conjugating GST isozymes and MRP family members. Using a variety of model cell lines developed in our laboratory, I am examining the hypothesis that MRP and GST act synergistically to confer MDR. Additionally, I am investigating the role in protection from carcinogen and other xenobiotics toxicities played by combined expression of xenobiotic conjugating and drug efflux systems.

Recently, we have begun investigations on the role of glutathione conjugation and conjugate efflux in the modulation of the biological, including anti-tumor, activities of potent cellular eicosinoids.


Recent Publications (selected):

C.M. Paumi, M. Wright, A.J. Townsend, C.S. Morrow. Multidrug resistance protein (MRP) 1 and MRP3 attenuate cytotoxic and transactivating effects of the cyclopentenone prostaglandin, 15-deoxy-?12,14prostaglandin J2 in MCF7 breast cancer cells. Biochemistry 42: 5429-5437, 2003.

A. J. Townsend, S. L. Kabler, J. Doehmer, C. S. Morrow. Modeling the metabolic competency of glutathione S-transferases (GSTs) using genetically modified cell lines. Toxicology 181-182: 265-269, 2002.

S.K. Diah, P.K. Smitherman, J. Aldridge, E.L. Volk, E. Schneider, A.J. Tounsend, C.S. Morrow. Resistance to Mitoxantrone in MRP1-expressing MCF7 Breast Cancer Cells: Characterization of Mitoxantrone Transport. Cancer Res. 61: 5461-5467, 2001.

Paumi, C.M., B.G. Ledford, P.K. Smitherman, A.J. Townsend, C.S. Morrow. Role of multidrug resistance protein 1 (MRP1) and glutathione S-transferase A1-1 in alkylating agent resistance: Kinetics of glutathione conjugate formation and efflux govern differential cellular sensitivity to chlorambucil versus melphalan toxicity, J. Biol. Chem. 276: 7952-7956, 2001.

C.S. Morrow, P.K. Smitherman, A.J. Townsend. Role of multidrug resistance protein 2 in glutathione S-transferase P1-1-mediated resistance to 4-nitroquinoline 1-oxide toxicities in HepG2 cells. Mol. Carcinogenesis 29: 170-178, 2000.

W. R. Fields, C. S. Morrow, Doehmer, J., A. J. Townsend. Expression of stably transfected murine glutathione S-transferase A3-3 protects against nucleic acid alkylation and cytotoxicity by aflatoxin B1 in hamster V79 cells expression rat cytochrome P450-2B1. Carcinogenesis 20: 1121-1125, 1999.

S. K. Diah, P. K. Smitherman, A. J. Townsend, and C. S. Morrow. Detoxification of 1-chloro-2,4-dinitrobenzene (CDNB) in MCF7 breast cancer cells expressing glutathione S-transferase P1-1 and/or multidrug resistance protein 1. Toxocol. Appl. Pharmacol. 157: 85-93, 1999.

C. S. Morrow, P. K. Smitherman, S. K. Diah, E. Schneider, and A. J. Townsend. Coordinated action of glutathione S-transferases (GST) and multidrug resistance protein 1 (MRP1) in antineoplastic drug detoxification: Mechanism of GST A1-1- and MRP1-associated resistance to chlorambucil in MCF7 breast carcinoma cells. J. Biol. Chem. 273: 20114-20120, 1998.

C. S. Morrow, S. Diah, P. K. Smitherman, E. Schneider, A. J. Townsend. Multidrug resistance protein and glutathione S-transferase P1-1 act in synergy to confer protection from 4-nitroquinline 1-oxide toxicity. Carcinogenesis 19: 109-115, 1998.