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William E. Fahl, Ph.D.

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Bill FahlProfessor 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: 6455 Wisconsin Institutes for Medical Research
Telephone:
Office - (608) 262-1275; Lab - (608) 262-7499
Email: fahl@oncology.wisc.edu

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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

Fahl, W. E.  Effect of Topical Vasoconstrictor Exposure Upon Tumoricidal Radiotherapy.  Int. J. Cancer, 135(4): 981-988, 2014.

Soref, C. M., and Fahl, W. E.  A New Topical Vasoconstrictor-based Strategy for Prevention of Oral Mucositis.  Oral Surg. Oral Med. Oral Pathol. Oral Radiol., 117(4): 454-461, 2014.

Soref, C. M., and Fahl, W. E.  A New Strategy to Prevent Chemotherapy and Radiotherapy-Induced Alopecia Using Topically Applied Vasoconstrictor.  Int. J. Cancer, in press, 2014 [Epub ahead of print May 8 2014].

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., 89(7): 485-492, 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.

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