Billy W. Day is professor of pharmaceutical sciences, with secondary appointments in chemistry, environmental & occupational health and the clinical translational science institute, and a visiting professor appointment in computational biology, at the University of Pittsburgh. He is also the director of medicinal chemistry in the University of Pittsburgh Drug Discovery Institute. He received the B.S. in chemistry and biology from Oklahoma City University in 1982. He obtained the Ph.D. in pharmaceutical sciences (medicinal chemistry) from the University of Oklahoma in 1988, working on the design, synthesis and biological evaluation of antiestrogens. He did his postdoctoral training in chemistry and toxicology at the Massachusetts Institute of Technology, studying the formation, detection and quantitation of carcinogen metabolite-protein adducts. He joined the faculty at the University of Pittsburgh in 1991. Professor Day's research has centered on the chemistry and pharmacology/toxicology of cancer, particularly anti-tubulin/microtubule agents, antiestrogens, anti-topoisomerase II agents, and nitric oxide and pro/anti-oxidant biochemistry, although work in recent years has also included agents that alter the innate immune response, alter signaling pathways important for damaged organ repair/repopulation, inhibit HIV 1-host cell protein-protein interactions, and inhibitors/enhancers of the molecular motor protein complex cytoplasmic dynein. His lab designs and synthesizes potential drugs/chemical biology tools, then performs biochemical and cell biological evaluations of them (along with a large number of other chemicals provided by a variety of collaborators). The lab also performs radio- and stable isotope-labeled syntheses. The biological evaluations include a large mass spectrometry-based component, i.e., metabolite identification, as well as discovery and structure elucidation of biomarkers of effect or predisposition, and their quantitative analyses via stable isotope methodologies. All of the chemical and biological data is used for computational redesign and/or building of predictive tools, such as quantitative structure-activity relationships or pathway perturbation analyses.
Daghestani, H.N., Day, B.W. Theory and applications of surface plasmon resonance, resonant mirror, resonant waveguide grating, and dual polarization interferometry biosensors. Biosensors 2011, 10, 9630-9646.
Cherra, S.J. III, Kulich, S.M., Uechi, G.T., Balasubramani, M., Mountzouris, J., Day, B.W., Chu, C.T. Regulation of the autophagy protein LC3 by phosphorylation. J. Cell Biol. 2010, 190, 533-539.
Zhu, W., Jiménez, M., Jung,, W.-H., Camarco, D.P., Balachandran, R., Vogt, A., Day, B.W., Curran, D.P. Streamlined syntheses of (–)-dictyostatin, 25,26-dihydro-16-desmethyldictyostatin, and 6-epi-25,26-dihydro-16-desmethyldictyostatin. J. Am. Chem. Soc. 2010, 132, 9175-9187.
Vogt, A., Codore, H., Day, B.W., Hukriede, N.A., Tsang, M. Development of automated imaging and analysis for zebrafish chemical screens. J. Vis. Exp. 2010, Jun 24;(40). pii:1900. doi:10.3791/1900.
de Groh, E.D., Swanhart, L.M., Cosentino, C.C., Jackson, R.L., Dai, W., Kitchens, C.A., Day, B.W., Smithgall, T.E., Hukriede, N.A. Inhibition of histone deacetylase expands the renal progenitor cell population. J. Am. Soc. Nephrol. 2010, 21, 794-802.
Lakshman, M.K., Singh, M.K., Parrish, D., Balachandran, R., Day, B.W. Azide-tetrazole equilibrium of C-6 azidopurine nucleosides and their ligation reactions with alkynes. J. Org. Chem. 2010, 75, 2461-2473.
Beckner, M.E., Fellows-Mayle, W., Zhang, Z., Agostino, N.R., Kant, J.A., Day, B.W., Pollack, I.F. Identification of ATP Citrate Lyase as a positive regulator of glycolytic function in glioblastomas. Int. J. Cancer 2010, 126, 2282-2295.
You, Z., Gao, H., Gao, J., Shin, P.H., Day, B.W., Wang, Y. A functionalizable polyester with free hydroxyl groups and tunable physiochemical and biological properties. Biomaterials 2010, 31, 3129-3138.
Emert-Sedlak, L., Kodama, T., Lerner, E.C., Dai, W., Foster, C., Day, B.W., Lazo, J.S., Smithgall, T.E. Chemical library screens targeting an HIV-1 accessory factor/host cell kinase complex identify novel anti-retroviral compounds. ACS Chem. Biol. 2009, 4, 939-947.
Fan, Y., Schreiber, E.M., Day, B.W. Human liver microsomal metabolism of (+)-discodermolide. J. Nat. Prod. 2009, 72, 1748-1754.
Vogt, A., McPherson, P.A., Shen, X., Balachandran, R., Zhu, G., Raccor, B.S., Nelson, S.G., Tsang, M., Day, B.W. High-content analysis of cancer cell-specific apoptosis and inhibition of in vivo angiogenesis by synthetic (–)-pironetin and analogs. Chem. Biol. Drug Des. 2009, 74, 358-368.
Kangani, C.O., Day, B.W. A novel and direct synthesis of 1,3,4-oxadiazoles or oxazolines from carboxylic acids using cyanuric chloride/indium. Tetrahedron Lett. 2009, 50, 5332-5335.
Albert, B.J., McPherson, P.A., O’Brien, K., Czaicki, N.L., DeStefino, V., Osman, S., Li, M., Day, B.W., Grabowski, P.J., Moore, M.J., Vogt, A., Koide, K. Meayamycin inhibits pre-messenger RNA splicing and exhibits picomolar activity against multidrug-resistant cells. Mol. Cancer Ther. 2009, 8, 2308-2318.
Daghestani, H.D., Fernig, D.G., Day, B.W. Evaluation of biosensor surfaces for the detection of microtubule perturbation. Biosens. Bioelectron. 2009, 24, 136-141.
Molina, G., Vogt, A., Bakan, A., Dai, W., Queiroz de Olivera, P., Znosko, W., Smithgall, T.E., Bahar, I., Lazo, J.S., Day, B.W., Tsang, M. Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages. Nat. Chem. Biol. 2009, 5, 680-687.
Gao, X., Kuruba, R., Damodaran, K., Day, B.W., Liu, D., Li, S. Polyhydroxylalkyleneamines: a class of hydrophilic cationic polymer-based gene transfer agents. J. Control. Release 2009, 137, 38-45.
Brummond, K.M., Mao, S., Shinde, S.N., Johnston, P.J., Day, B.W. Design and synthesis of a library of tetracyclic hydroazulenoisoindoles. J. Comb. Chem. 2009, 11, 486-494.
Sarachine, M.J., Janjic, J.M., Wipf, P., Day, B.W. Biphenyl C-cyclopropylalkylamides: New scaffolds for targeting estrogen receptor β. Bioorg. Med. Chem. Lett. 2009, 19, 2404-2408.
Chiang, A.N., Valderramos, J.-C., Balachandran, R., Chovatiya, R.J., Mead, B.P., Schneider, C., Bell, S.L., Klein, M.G., Huryn, D.M., Chen, X.S., Day, B.W., Fidock, D.A., Wipf, P., Brodsky, J.L. Select pyrimidinones inhibit the propagation of the malarial parasite, Plasmodium falciparum. Bioorg. Med. Chem. 2009, 17, 1527-1533.
Tierno, M.B., Petrik, B., Graham, T.H., Wipf, P., Xu, F., Saunders, W., Kitchens, C.A., Raccor, B.S., Balachandran, R., Day, B.W., Stout, J.R., Walczak, C.E., Ducruet, A.P., Hindman, C.E., Lazo, J.S. Microtubule binding and disruption and induction of premature senescence by disorazole C1. J. Pharmacol. Exp. Ther. 2009, 328, 715-722.
Su, Y., Fu, C., Ishikawa, S., Stella, A., Kojima, M., Shitoh, K., Schreiber, E.M., Day, B.W., Liu, B. APC is essential for targeting phosphorylated β-catenin to the SCFb-TrCP ubiquitin ligase. Mol. Cell 2008, 32, 652-661.
Dietrich, D.R., Heussner, A.H., O?Brien, E., Grammatté, T., Runkel, M., Rumpf, S., Day, B.W. Propiverine-induced accumulation of nuclear and cytosolic protein in F344 rat kidneys: isolation and identification of the accumulating protein. Toxicol. Appl. Pharmacol. 2008, 233, 411-419.
Eiseman, J.L, Bai, L., Jung, W.-H., Moura-Letts, G., Day, B.W., Curran, D.P. Improved synthesis of 6-epi-dictyostatin and antitumor efficacy in mice bearing MDA-MB231 human breast cancer xenografts. J. Med. Chem. 2008, 51, 6650-6653.
Gibson, F., Anderson, L., Babnigg, G., Baker, M., Berth, M., Binz, P.-A., Borthwick, A., Cash, P., Day, B.W., Friedman, D.B., Garland, D., Gutstein, H.B., Hoogland, C., Jones, N.A., Jones, A.R., Khan, A., Klose, J., Lamond, A.I., Lemkin, P.F., Lilley, K.S., Minden, J., Morris, N.J., Paton, N.W., Pisano, M.R., Prime, J.E., Rabilloud, T., Stead, D.A., Taylor, C.F., Voshol, H., Wipat, A. Guidelines for reporting the use of gel electrophoresis in proteomics. Nat. Biotechnol. 2008, 26, 863-864.
Kangani, C.O., Day, B.W. Mild, efficient Friedel-Crafts acylation from carboxylic acids using cyanuric chloride and AlCl3. Org. Lett. 2008, 10, 2645-2648.
Wright, C.M., Chovatiya, R.J., Jameson, N.E., Turner, D.M., Zhu, G., Werner, S., Huryn, D.M., Pipas, J.M., Day, B.W., Wipf, P., Brodsky, J.L. Pyrimidinone-peptoid hybrid molecules with distinct effects on molecular chaperone function and cell proliferation. Bioorg. Med. Chem. 2008, 16, 3291-3301.
Raccor, B.S., Vogt, A., Sikorski, R.P., Madiraju, C., Balachandran, R., Shin, Y., Fukui, Y., Jung, W.-H., Curran, D.P., Day, B.W. Cell-based and biochemical structure-activity analyses of analogues of the microtubule stabilizer dictyostatin. Mol. Pharmacol. 2008, 73, 718-726.