B.S., 1972, Zoology/Chemistry, University of Wisconsin-Madison
Ph.D., 1975, Physiology/Oncology, University of Wisconsin-Madison
Postdoctoral research: University of Wisconsin-Madison
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.
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.
Brand M, Sommer M, Jermusek F Jr, Fahl WE, Uder M. Reduction of X-ray-induced DNA damage in normal human cells treated with the PrC-210 radioprotector. Biol Open. 2018 Aug 22. pii: bio.035113. doi: 10.1242/bio.035113. [Epub ahead of print] PubMed PMID: 30135082.
Jermusek F Jr, Benedict C, Dreischmeier E, Brand M, Uder M, Jeffery JJ, Ranallo FN, Fahl WE. Significant Suppression of CT Radiation-Induced DNA Damage in Normal Human Cells by the PrC-210 Radioprotector. Radiat Res. 2018 Aug;190(2):133-141. doi: 10.1667/RR14928.1. Epub 2018 May 21. PubMed PMID: 29781766. PubMed Central PMCID: PMC6083833
Cleary JF, Anderson BM, Eickhoff JC, Khuntia D, Fahl WE. Significant suppression of radiation dermatitis in breast cancer patients using a topically applied adrenergic vasoconstrictor. Radiat Oncol. 2017 Dec 22;12(1):201. doi: 10.1186/s13014-017-0940-7. PubMed PMID: 29273054; PubMed Central PMCID: PMC5741935.
Fahl WE. Complete prevention of radiation-induced dermatitis using topical adrenergic vasoconstrictors. Arch Dermatol Res. 2016 Dec;308(10):751-757. PubMed PMID: 27704205.
Graul-Conroy A, Hicks EJ, Fahl WE. Equivalent chemotherapy efficacy against leukemia in mice treated with topical vasoconstrictors to prevent cancer therapy side effects. Int J Cancer. 2016 Jun 15;138(12):3011-9. doi: 10.1002/ijc.30037. Epub 2016 Mar 2. PubMed PMID: 26860340.
Soref CM, Fahl WE. A new strategy to prevent chemotherapy and radiotherapy-induced alopecia using topically applied vasoconstrictor. Int J Cancer. 2015 Jan 1;136(1):195-203. doi: 10.1002/ijc.28961. Epub 2014 May 16. PubMed PMID: 24811525; PubMed Central PMCID: PMC4342350.
Soref CM, Fahl WE. Optimum topical delivery of adrenergic agonists to oral mucosa vasculature. Pharm Res. 2015 Feb;32(2):492-9. doi: 10.1007/s11095-014-1477-1. Epub 2014 Jul 31. PubMed PMID: 25079392; PubMed Central PMCID: PMC4324606.
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.
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.