Dean's Office Staff

Howard D. Beall

Professor & Associate Dean

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Personal Summary

Howard Beall arrived at The University of Montana in July 1997 as an Assistant Professor. He earned a Ph.D. in Medicinal Chemistry at the University of Florida in 1991 under the supervision of Professor Kenneth Sloan. He completed postdoctoral training in biochemical and molecular toxicology under the guidance of Professor David Ross at the University of Colorado Health Sciences Center and served there as an Assistant Research Professor and Assistant Professor before coming to UM. He was promoted to Associate Professor in September 2000 and Professor in 2008. Dr. Beall is currently the Associate Dean for Pharmacy, the chief academic officer for the Skaggs School of Pharmacy.

Education

B.S. Pharmacy, University of Montana

M.S. Pharmacy, University of Florida

Ph.D. Medicinal Chemistry, University of Florida

Courses Taught

PHAR 331 - Pharmaceutics

PHAR 362 - Pharmaceutical Sciences Laboratory II

PHAR 422 - Medicinal Chemistry II

Research Interests

1. Anthracenyl isoxazole amide antitumor agents (AIMs). The ability of these agents to bind G-quadruplex DNA sequences that are prevalent in telomeres, oncogene promoters and mitochondria was discovered somewhat serendipitously. Initially studied by Dr. Nick Natale for their potential to bind B-DNA sequences in HIV and tumor cells, AIMs were inactive against HIV, and NCI COMPARE analysis suggested that they did not act as traditional B-DNA binding agents. Our recent work has focused on proving the G-quadruplex binding hypothesis, which has resulted in several recent proposals. I joined the collaboration in 2008 due to my expertise with tumor cell-based assays, imaging and spectroscopy.

a. Gajewski, M.P., Beall, H., Schneider, M., Stranahan, S.M., Mosher, M.D., Rider, K.C. and Natale, N.R. Bis-anthracenyl isoxazolyl amides have enhanced anticancer activity. Bioorg. Med. Chem. Lett. 19:4067-4069 (2009); PMID: 19560922.

b. Mirzaei, Y.R., Weaver, M.J., Steiger, S.A., Kearns, A.K., Gajewski, M.P., Rider, K.C., Beall, H.D. and Natale, N.R. Improved synthesis of 3-aryl isoxazoles containing fused aromatic rings. Tetrahedron 68:10360-10364 (2012); PMID: 23526841.

c. Duncan, N.S., Beall, H.D., Kearns, A.K., Li, C. and Natale, N.R. Ethyl 3-(9-chloro-10-oxo-9,10-dihydroanthracen-9-yl)-5-methylisoxazole-4-carboxylate. Acta Cryst. E70:o315-o316 (2014); PMID: 2476501615.

d. Weaver, M.J., Kearns, A.K., Stump, S., Li, C., Gajewski, M.P., Rider, K.C., Backos, D.S., Reigan, P.R., Beall, H.D.* and Natale, N.R.* AIMing towards improved antitumor efficacy. Bioorg. Med. Chem. Lett. 25:1765-1770 (2015); PMID: 25782743.

2. NQO1-directed antitumor agents. The phrase, “enzyme-directed bioreductive drug development” was first published by Workman and Walton in 1990. My interest in NQO1 (NADP(H):quinone oxidoreductase 1) as a key target for development of antitumor drugs began during my postdoctoral fellowship in 1991 with Dr. David Ross at the University of Colorado and has been a major focus of my work ever since. The discovery that NQO1 was markedly overexpressed in solid tumors from many tissues was the key event in this field. Our work has led to the identification of many highly selective antitumor quinones along with a patent and licensing agreement for the benzoquinone, RH1.

a. Hassani, M., Cai, W., Koelsch, K.H., Holley, D.C., Rose, A.S., Olang, F., Lineswala, J.P., Holloway, W.G., Gerdes, J.M., Behforouz, M. and Beall, H.D. Lavendamycin antitumor agents: structure-based design, synthesis and NAD(P)H:quinone oxidoreductase 1 (NQO1) model validation with molecular docking and biological studies. J. Med. Chem. 51:3104-3115 (2008); PMID: 18457384.

b. Cai, W., Hassani, M., Karki, R., Walter, E.D., Koelsch, K.H., Seradj, H., Lineswala, J.P., Mirzaei, H., York, J.S., Olang, F., Sedighi, M., Lucas, J.S., Eads, T.J., Rose, A.S., Charkhzarrin, S., Hermann, N.G., Beall, H.D.* and Behforouz, M.* Synthesis, metabolism, and in vitro cytotoxicity studies on novel lavendamycin antitumor agents. Bioorg. Med. Chem. 18:1899-1909 (2010); PMID: 20149966.

c. Newsome, J.J., Hassani, M., Swann, E., Bibby, J.M., Beall, H.D. and Moody, C.J. Benzofuran-, benzothiophene-, indazole- and benzisoxazolequinones: excellent substrates for NAD(P)H:quinone oxidoreductase 1. Bioorg. Med. Chem. 21:2999-3009 (2013); PMID: 23635904.

d. Keyari, C.M., Kearns, A.K., Duncan, N.S., Eickholt, E.A., Abbott, G., Beall, H.D.* and Diaz, P.* Synthesis of new quinolinequinone derivatives and preliminary exploration of their cytotoxic properties. J. Med. Chem., 56:3806-3819 (2013); PMID: 23574193.

3. Arsenic and cardiovascular disease. Epidemiologic studies have linked arsenic exposure via drinking water to cardiovascular diseases, but the mechanisms involved are still unclear. In 2004 we showed that arsenic in drinking water significantly increased atherosclerotic plaque formation in ApoExLDLR double knockout mice. Our mechanistic work focused on release of inflammatory mediators and generation of reactive oxygen and nitrogen species in cells in response to arsenic exposure and the regulatory molecules and pathways involved in atherosclerosis and vascular development.

a. Bunderson, M., Coffin, J.D. and Beall, H.D. Arsenic induces peroxynitrite generation and cyclooxygenase-2 (COX-2) protein expression in aortic endothelial cells: possible role in atherosclerosis. Toxicol. Appl. Pharmacol. 184:11-18 (2002); PMID: 12392964.

b. Bunderson, M., Brooks, D.M., Walker, D.L., Rosenfeld, M.E., Coffin, J.D. and Beall, H.D. Arsenic exposure exacerbates atherosclerotic plaque formation and increases nitrotyrosine and leukotriene biosynthesis. Toxicol. Appl. Pharmacol. 201:32-39 (2004); PMID: 15519606.

c. Bunderson, M., Pereira, F., Schneider, M.C., Shaw, P.K., Coffin, J.D. and Beall, H.D. Manganese enhances peroxynitrite and leukotriene E4 formation in bovine aortic endothelial cells exposed to arsenic. Cardiovasc. Toxicol. 6:15-24 (2006); PMID: 16845179.

d. Pereira, F.E., Coffin, J.D. and Beall, H.D. Activation of protein kinase C and disruption of endothelial monolayer integrity by sodium arsenite – potential mechanism in the development of atherosclerosis. Toxicol. Appl. Pharmacol. 220:164-177 (2007); PMID: 17306850.