people
|Faculty
|Billy Day
 |
Billy Day 3501 Fifth Avenue |
Synthesis of Antitumor Agents
A major focus of our research is synthesis of libraries of potential antitumor agents. As examples, we developed a concise and steroselective route to intermediates useful for preparation of polyketide/polypropionate natural products, and have developed a combinatorial method featuring both solid- and solution-phase methods for synthesis of 1,2-di- and 1,1,2-triarylcyclopropyl compounds as potential anti-tumor agents. Other synthetic projects in the lab include preparation of radio- and stable isotope-labeled forms of drugs, toxins and metabolites, as well as photoaffinity probes for mechanistic studies.
Molecular Pharmacology and Toxicology
Beyond the preparation of libraries of agents, we also examine their biological properties. Additionally, we use to great advantage the synthetic prowess of our outstanding colleagues here in the Department (e.g., Profs. Curran, Nelson and Wipf), testing libraries that their groups have prepared. We perform a variety of high throughput biochemical and cell-based assays for endpoints, such as tubulin polymerization perturbation and cancer cell antiproliferative and mitotic block activity, as well as high information content cell-based assays (i.e., multiparameter fluorescence quantitative measures of targets and signaling cascades within cells). All of this data is used for development of Quantitative Structure-Activity Relationship computational models that are reiterated into our drug design schemes.
Proteomics
The study of the protein complement of cells, tissues and organisms provides a vast amount of information useful in disease detection, prevention, control and treatment. The proteome is a highly dynamic and complex entity, and sophisticated experimental design and instrumentation is necessary to evaluate it. We have a variety of mass spectrometric tools, including MALDI-TOF-MS's, a MALDI-TOF/TOF-MS, and an ESI-ion trap-MS, and an ESI-TOF-MS to apply to proteomics studies, and collaborate extensively with groups across the campus in these pursuits.
Awards
Special Review Panel for Targeting Diseases Caused by Protein Misfolding or Misprocessing, NIH (2006); Developmental Therapeutics (DT) Study Section, Ad hoc, NIH (2005); Drug Development P01 Cluster Review Panel, NIH (2005); Special Emphasis Panel, National Cooperative Drug Discovery Groups in Cancer, National Cancer Institute (2004); Innovative Therapies Review Group, California Breast Cancer Research Program (2004-present); Drug Discovery and Molecular Pharmacology (DMP) Study Section, Ad hoc, NIH (2003); Guest Professor, Universität Konstanz, Facultät für Biologie, Germany (1997, 1999, 2002, 2003); Member of the Editorial Advisory Board, Chemical Research in Toxicology (2002-2004); Special Review Panel, Innovative Toxicology Models for Drug Evaluation Program, National Cancer Institute (2002-2004); Cancer Drug Development Peer Review Committee, American Cancer Society (2001-Present); Member of the Chemistry in Cancer Research Task Force, American Association for Cancer Research (2000-Present); Keynote Speaker, NSF Undergraduate Faculty Enhancement Program, University of Southern Mississippi (1992); Invited Speaker, International Conference on Monitoring Toxic Chemicals and Biomarkers, Berlin, Germany (1992); NIH, MIT Hazardous Substances Management Program and American Cancer Society Postdoctoral Fellowships, Dept. Chemistry, Div. Toxicology and George R. Harrison Spectroscopy Lab, MIT (1988-1991); John B. Bruce Memorial Outstanding Graduate Student in Medicinal Chemistry Award, Univ. Oklahoma (1988); American Institute of Chemists Outstanding Senior Chemistry Student, Oklahoma City Univ. (1982); NSF Undergraduate Summer Research Fellowship (Physical Biochemistry), Oklahoma State Univ. (1981)
Selected Publications
"Brisk production of nitric oxide and associated formation of S-nitrosothiols in early hemorrhage," Atkins, J.L., Day, B.W., Handrigan, M.T., Zhang, Z., Pamnani, M.B., Gorbunov, N.V., J. Appl. Physiol., 2006, 100, 1267-1277
"Synthesis and biological evaluation of purealin and analogues as cytoplasmic dynein heavy chain inhibitors," Zhu, G., Yang, F., Balachandran, R., Höök, P., Vallee, R., Curran, D.P., Day, B.W., J. Med. Chem., 2006, 49, 2063-2076
"Rac1 leads to phosphorylation-dependent increase in stability of the p66shc adaptor protein: role in Rac1-induced oxidative stress," Khanday, F.A., Yamamori, T., Mattagajasingh, I., Zhang, Z., Bugayenko, A., Naqvi, A., Santhanam, L., Nabi, N., Kasuno, K., Day, B.W., Irani, K., Mol. Biol. Cell, 2006, 17, 122-129
"Orphan nuclear receptor PXR sensitizes oxidative stress responses in transgenic mice and cancerous cells," Gong, H., Singh, S.V., Singh, S.P., Mu, Y., Saini, S.P.S., Toma, D. Ren, S. Kagan, V.E., Day, B.W. Zimniak, P., Xie, W., Mol. Endocrinol., 2006, 20, 279-290
"Fluorous mixture synthesis of (–)-dictyostatin and three stereoisomers," Fukui, Y., Brückner, A.M., Shin, Y., Balachandran, R., Day, B.W., Curran, D.P., Org. Lett., 2006, 8, 301-304
"Altered expression and localization of creatine kinase B, heterogenous nuclear ribonucleoprotein F and high mobility group box 1 protein in the nuclear matrix associated with colon cancer," Balasubramani, M., Day, B.W., Schoen, R.E., Getzenberg, R.H., Cancer Res., 2006, 66, 763-769
"Proteomic characterization of harvested pseudopodia with differential gel electrophoresis and specific antibodies," Beckner, M.E., Chen, X., An, J., Day, B.W., Pollack, I.F., Lab. Invest., 2005, 85, 316-327
"Systems cell biology knowledge created from high content screening," Giuliano, K.A., Cheung, W.S., Curran, D.P., Day, B.W., Kassick, A.J., Lazo, J.S., Nelson, S.G., Shin, Y., Taylor, D.L., Assay Drug Dev. Technol., 2005, 3, 501-514
"Tubulin assembly, taxoid site binding and cellular effects of the microtubule-stabilizing agent dictyostatin," Madiraju, C., Edler, M.C., Hamel, E., Raccor, B.S., Balachandran, R., Zhu, G., Giuliano, K.A., Vogt, A., Shin, Y., Fournier, J.-H., Fukui, Y., Brückner, A.M., Curran, D.P., Day, B.W., Biochemistry, 2005, 44, 15053-15063
"Redox regulation of Cdc25B by cell active quinolinediones," Brisson, M., Nguyen, T., Wipf, P., Joo, B., Day, B.W., Skoko, J.S., Schreiber, E.M., Foster, C., Bansal, P., Lazo, J.S., Mol. Pharmacol., 2005, 68, 1810-1820