William E. Fahl, Ph.D.
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, chemotherapy or radiation-induced 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, cancer therapy, metabolism of environmental toxicants or exposure to ionizing radiation. We approach this goal using two strategies: (1) the 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) the design and synthesis of a new generation of bifunctional aminothiol radioprotector molecules, which are administered systemically; these molecules scavenge oxygen free radicals and reversibly bind to DNA to create a reversible, G1/S phase cell cycle block. The prototype of this family of low molecular weight aminothiols confers complete protection against an otherwise 100% lethal dose of gamma radiation to mice or rats. This combination of efficient oxygen free radical scavenging and reversible cell cycle block provides an effective, next generation, systemic radioprotector suitable for military, civil defense and related applications.
In both strategies (1) and (2) above, significant research is also done to optimize pharmaceutical formulation and delivery of the active agent drugs to at-risk cell populations. This involves optimization of often conflicting elements of drug solubility, mammalian pharmacokinetics and metabolism/activation of prodrug forms to achieve pharmacologic efficacy in target cell populations.
Selected patents
US 8,114,914: Fahl, W.E., Ruoho, A.E., and Mehta, M. Topical vasoconstrictor preparations and methods for protecting cells during cancer chemotherapy and radiotherapy.
US 8,247,457: Fahl, W.E., Ruoho, A.E., and Mehta, M. Topical vasoconstrictor preparations and methods for protecting cells during cancer chemotherapy and radiotherapy.
US 7,314,959: Fahl, W.E., Peebles, D.D., Copp, R.C. Amino Thiol Compounds and Compositions for Use in Conjunction with Cancer Therapy.
US 7,414,154: Fahl, W.E., Copp, R.C., Ochsner, C.E., Peebles, D. D. and Fahl, K.L. Polyamine Compounds and Compositions for Use in Conjunction with Cancer Therapy.
US 6,136,605: Fahl, W.E., Gulick, A.M., Manoharan, T.H., Puchalski, R.B., Kramer, K. and Wasserman, W.W. Glutathione S-Transferase Isoforms.
US 6,040,424: Fahl, W.E. and Wasserman, W.W. Protein and Gene for Antioxidant Response.
Selected recent publications
Copp, R. R., Peebles, D. D., Soref, C. M., and Fahl, W. E. Radioprotective Efficacy and Toxicity of a New Family of Aminothiol Analogs. Int. J. Radiat. Biol., in press, 2013 [Epub ahead of print Jan 31 2013].
Peebles, D. D., Soref, C. M., Copp, R. R., Thunberg, A. L., and Fahl, W. E. ROS-Scavenger and Radioprotective Efficacy of the New PrC-210 Aminothiol. Radiat. Res., 178: 57-68, 2012.
Soref, C. M., Hacker, T. A., and Fahl, W. E. A New Orally Active, Aminothiol Radioprotector-Free of Nausea and Hypotension Side Effects at Its Highest Radioprotective Doses. Int. J. Radiat. Oncol., 82: e701-e707, 2012.
Copp, R. R., Peebles, D. D., and Fahl, W. E. Synthesis and Growth Regulatory Activity of a Prototype Member of a New Family of Aminothiol Radioprotectors. Bioorg. Med. Chem. Lett., 21: 7426-7430, 2011.