Professor of
Oncology
B.S., 1972, Zoology/Chemistry, University of Wisconsin-Madison
Ph.D., 1975, Physiology/Oncology, University of Wisconsin-Madison
Postdoctoral research: University of Wisconsin-Madison
Office: 321A McArdle Laboratory
Telephone: Office - (608) 262-1275; Lab - (608) 262-7499
Email: fahl@oncology.wisc.edu
Research Interests: Genome protection against natural, environmental or chemotherapy toxins
Research Description: The research in our laboratory is designed to enable cells to protect their genomes against toxic molecules, whether the toxins are formed during normal oxidative life, during cancer therapy or during the metabolism of environmental toxicants. We approach this goal using two strategies: (1) the direct design, synthesis and pharmaceutical application of protective drug molecules to at-risk epithelial cells in hair follicles, oral mucosa, etc., first tested in animal models then in clinical studies of target cells in cancer patients to prevent alopecia, oral mucositis, etc. induced by cancer therapy; and (2) identification of proteins that interact with and regulate gene expression through the Antioxidant Responsive Element (ARE; or, Electrophile Response Element). This regulatory element is present in the promoter region of genes that compose the Chemoprotective Response battery of genes that are expressed by cells in response to toxin exposure; we focus primarily upon one of these genes that encodes a glutathione S-transferase. The study of ARE-activating transcription factors in our laboratory will enable development of rationally designed chemoprotective molecules for humans that will impact carcinogenesis, aging, and damage from stroke and myocardial infarct.
Pi, J., Bai, Y., Reece, J. M., Williams, J., Liu, D., Freeman, M. L., Fahl, W. E., Shugar, D., Liu, J., Qu, W., Collins, S., and Waalkes, M. P. Molecular Mechanism of Human Nrf2 Activation and Degradation: Role of Sequential Phosphorylation by Protein Kinase CK2. Free Radic. Biol. Med., 42: 1797-1806, 2007.
Raghavachari, N., and Fahl, W. E. Targeted Gene Delivery to Skin Cells In Vivo: A Comparative Study of Liposomes and Polymers as Delivery Vehicles. J. Pharm. Sci., 91: 615-622, 2002.
Zhu, M., and Fahl, W. E. Functional Characterization of Transcription Regulators That Interact with the Electrophile Response Element. Biochem. Biophys. Res. Commun., 289: 212-219, 2001.
Zhu, M., Chapman, W. G., Oberley, M. J., Wasserman, W. W., and Fahl, W. E. Polymorphic Electrophile Response Elements in the Mouse Glutathione S-Transferase GSTa1 Gene That Confer Increased Induction. Cancer Lett., 164: 113-118, 2001.
Yu, R., Mandlekar, S., Lei, W., Fahl, W. E., Tan, T.-H., and Kong, A.-N. T. p38 Mitogen-activated Protein Kinase Negatively Regulates the Induction of Phase II Drug-metabolizing Enzymes That Detoxify Carcinogens. J. Biol. Chem., 275: 2322-2327, 2000.
Zhu, M., and Fahl, W. E. Development of a Green Fluorescent Protein Microplate Assay for the Screening of Chemopreventive Agents. Anal. Biochem., 287: 210-217, 2000.
Zhu, M., Chapman, W. G., Oberley, M. J., Wasserman, W. W., and Fahl, W. E.Chemoprotection Conferred by Electrophile Responsive Element-Regulated Expression of Endogenous Glutathione S-Transferase Genes. Clin. Chem. Enzym. Comm., 8: 303-313, 2000.
Chaplen, F. W. R., Fahl, W. E., and Cameron, D. C. Evidence of High Levels of Methylglyoxal in Cultured Chinese Hamster Ovary Cells. Proc. Natl. Acad. Sci. USA, 95: 5533-5538, 1998.
Kujoth, G. C., Robinson, D. F., and Fahl, W. E. Binding of ETS Family Members Is Important for the Function of the c-sis/Platelet-derived Growth Factor-B TATA Neighboring Sequence in 12-O-Tetradecanoylphorbol-13-acetate-treated K562 Cells. Cell Growth & Different., 9: 523-534, 1998.
Mehta, M. P., Sinha, P., Kanwar, K., Inman, A., Albanese, M., and Fahl, W. E. Evaluation of Internet-Based Oncologic Teaching for Medical Students. J. Cancer Educat., 13: 197-202, 1998.
Manoharan, H.T., Gallo, J., Gulick, A.M., and Fahl, W.E. High-Level Production and Purification of Biologically Active Proteins from Bacterial and Mammalian Cells Using the Tandem pGFLEX Expression System. Gene, 193: 229-237, 1997.
Wasserman, W.W., and Fahl, W.E. Functional Antioxidant Responsive Elements. Proc. Natl. Acad. Sci. USA, 94: 5361-5366, 1997.
Gulick, A.M., and Fahl, W.E. Forced Evolution of Glutathione S-Transferase to Create a More Efficient Drug Detoxication Enzyme. Proc. Natl. Acad. Sci. USA, 92: 8140-8144, 1995.
