Current Research:

A major focus of the Day lab is synthesis of potential antitumor, anti-HIV and organ damage-reversal 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. Beyond the preparation of libraries of agents, their biological properties are also examined. Additionally, great advantage is taken of the synthetic prowess of outstanding colleagues here at Pitt through collaborative testing of libraries that their groups prepare. The Day lab performs 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, and multiparameter fluorescence quantitative measures of targets and signaling cascades within cells. All of this data is used for development of computational models that are reiterated into drug design schemes. Prof. Day also directs the University's Proteomics Core Lab, which provides mass spectrometric analyses of the protein complement of cells, tissues and organisms. The resulting vast amount of information is useful in disease detection, prevention, control and treatment. Sophisticated experimental design, instrumentation and data analysis tools are used to evaluate the proteome, and the lab collaborates extensively with many groups across the campus. His lab is presently working on discovery of biomarkers specific to progression of stage 0 (ductal carcinoma in situ) breast cancer by proteomics methods, as well as proteome changes in microtubule stabilizer-resistant breast cancer cells.

Bio:

Billy W. Day is professor of pharmaceutical sciences, with secondary appointments in chemistry and in environmental & occupational health, and a visiting professor appointment in computational biology, at the University of Pittsburgh. He is also the scientific director of the well equipped and staffed basic proteomics core lab of the University’s Schools of the Health Sciences. 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.