Funding is requested for years 32-36 of a highly successful Ph.D. program in pharmacology, the goal of which is to recruit and train research leaders at the intersection of chemistry biology, and medicine. The program fosters the development of independent investigators with expertise in the design and characterization of therapeutic agents and the study of their effects on living systems. Interdisciplinary training includes rigorous didactic teaching and intensive research training. Core courses in bioorganic chemistry, structural biology, biochemistry, molecular biology, cell biology, and bioinformatics provide the fundamental concepts of biomedical science. Our Graduate Pharmacology course teaches the quantitative foundations of pharmacology and the mechanisms of drug actions. Small group tutorials provide in-depth exploration of specific interest areas, and elective courses support focused training in areas ranging from analytical chemistry to clinical pharmacology. Students initiate research upon entering the program, performing laboratory research rotations in their first year in advance of selecting a thesis research advisor. Under the guidance of their thesis advisory committee, students execute significant research in the laboratory of one of 39 program faculty, each of whom direct vigorous research programs. Doctoral research areas include drug design, protein structure and function, glycobiology and lipid function, molecular imaging, virology, microbiology, oncology, and neuropharmacology. Students participate as speakers in pharmacology research seminars, journal clubs, and at national and international meetings. After completing their thesis research, students write a doctoral thesis, prior to presenting their doctoral studies at a public seminar. Since its inception, the program has awarded 181 Ph.D. degrees. There are 57 trainees currently in the program and enrollment averaged 11 per year for the past 5 years (range 8-16). Students typically obtain their Ph.D. degrees within 4-6 years. The training facilities include departmental and institutional classrooms, well-equipped labs, and outstanding core facilities. Students in the program have contributed meaningfully to biomedical discovery over the last decades, and graduates of the program hold research, teaching, and leadership positions throughout the world in top academic, industrial, and government institutions.
The development and refinement of new therapeutic agents is a major objective of modern medicine and of critical importance to the improvement of our nation's health. This Pharmacology Training Program proposal endeavors to train and equip the next generation of scientists who will take the lead in the basic and clinical science of drug discovery and development in academics, industry, and governmental sectors.
|Sanders, Sara; Vierling, Ryan J; Bartee, David et al. (2017) Challenges and Hallmarks of Establishing Alkylacetylphosphonates as Probes of Bacterial 1-Deoxy-d-xylulose 5-Phosphate Synthase. ACS Infect Dis 3:467-478|
|Seamon, Kyle J; Bumpus, Namandjé N; Stivers, James T (2016) Single-Stranded Nucleic Acids Bind to the Tetramer Interface of SAMHD1 and Prevent Formation of the Catalytic Homotetramer. Biochemistry 55:6087-6099|
|Calcaterra, Nicholas E; Hoeppner, Daniel J; Wei, Huijun et al. (2016) Schizophrenia-Associated hERG channel Kv11.1-3.1 Exhibits a Unique Trafficking Deficit that is Rescued Through Proteasome Inhibition for High Throughput Screening. Sci Rep 6:19976|
|Seamon, Kyle J; Stivers, James T (2015) A High-Throughput Enzyme-Coupled Assay for SAMHD1 dNTPase. J Biomol Screen 20:801-9|
|Seamon, Kyle J; Sun, Zhiqiang; Shlyakhtenko, Luda S et al. (2015) SAMHD1 is a single-stranded nucleic acid binding protein with no active site-associated nuclease activity. Nucleic Acids Res 43:6486-99|
|Hansen, Erik C; Seamon, Kyle J; Cravens, Shannen L et al. (2014) GTP activator and dNTP substrates of HIV-1 restriction factor SAMHD1 generate a long-lived activated state. Proc Natl Acad Sci U S A 111:E1843-51|
|Seamon, Kyle J; Hansen, Erik C; Kadina, Anastasia P et al. (2014) Small molecule inhibition of SAMHD1 dNTPase by tetramer destabilization. J Am Chem Soc 136:9822-5|
|Kalu, Nene N; Desai, Prashant J; Shirley, Courtney M et al. (2014) Nelfinavir inhibits maturation and export of herpes simplex virus 1. J Virol 88:5455-61|
|Schonhoft, Joseph D; Kosowicz, John G; Stivers, James T (2013) Correction to DNA translocation by human uracil DNA glycosylase: role of DNA phosphate charge. Biochemistry 52:8599|
|Lade, Julie M; Avery, Lindsay B; Bumpus, Namandjé N (2013) Human biotransformation of the nonnucleoside reverse transcriptase inhibitor rilpivirine and a cross-species metabolism comparison. Antimicrob Agents Chemother 57:5067-79|
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