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. PUBLIC HEALTH RELEVANCE: 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.