- 2016 Award in Excellence in Pharmacology/Toxicology
- 1984 Research Starter Grant in Pharmacology/Toxicology
- 1984 Faculty Development Award
Dr. James Halpert is Dean of the School of Pharmacy and Professor of Pharmacology and Toxicology at the University of Connecticut. He earned his B.A. in Scandinavian Languages from the University of California at Los Angeles in 1971, his Ph.D. in Biochemistry from Uppsala University, Sweden in 1977, and his M.S. in Toxicology from the Karolinska Institute, Sweden in 1978. After post-doctoral training with Dr. Robert A. Neal in the Center for Environmental Toxicology at Vanderbilt University, Dr. Halpert held a research assistant professor position at the Karolinska Institute from 1981-1983. Then he joined the faculty of the Department of Pharmacology and Toxicology at the University of Arizona. In 1991, Dr. Halpert was promoted to Professor and appointed as Assistant Director of the Center for Toxicology. In that capacity, he was the driving force behind the establishment of a center funded by the National Institute of Environmental Health Sciences (NIEHS) and was named Deputy Director. In 1998, he assumed the position of Professor and Chair of the Department of Pharmacology and Toxicology at the University of Texas Medical Branch in Galveston. There Dr. Halpert recruited 10 tenure-track faculty members, developed a program in Chemical Biology with support from the Robert A. Welch Foundation, and oversaw a five-fold increase in research funding in the department. From 1998-2004 he was a Foreign Adjunct Professor at the Karolinska Institute. Dr. Halpert also served from 2003-2008 as Director of the NIEHS Center in Galveston, Interim Director of the Sealy Center for Environmental Health and Medicine, and held the Mary Gibbs Jones Distinguished Chair in Environmental Toxicology. These centers encompassed basic science, clinical research, and community outreach, and a major focus was to develop translational research. In 2008, Dr. Halpert joined UCSD’s Skaggs School of Pharmacy and Pharmaceutical Sciences as Professor and Associate Dean for Scientific Affairs and was pivotal in the recruitment of 10 tenure-track faculty members and emergence of this new pharmacy school as one of the top 10 in NIH funding. In June 2014, he assumed his position at the University of Connecticut, where he has already been instrumental in obtaining of a joint award with Yale for a $10M Program in Innovative Therapeutics for Connecticut’s Health supported by the state.
Dr. Halpert’s research for the past 37 years has focused on the structure and function of cytochromes P450 (CYP) of the 2B and 3A subfamilies. Heterogeneity in the expression levels and/or activities of cytochromes P450 is a major determinant of individual response to medications and susceptibility to environmental toxicants. P450s contribute significantly to species differences in xenobiotic metabolism and hence to the proper choice of animal models for safety evaluation of drugs and other chemicals. CYP2B enzymes play a special role in the metabolism of environmental contaminants such as pesticides and polychlorinated biphenyls, whereas CYP3A4 metabolizes half of the clinically used drugs that require P450 action for elimination. Dr. Halpert’s Starter Grant and Faculty Development Award in 1984 were pivotal in subsequent receipt of a Research Career Development Award and an R01 grant from NIEHS on CYP2B enzymes, which has been funded continuously since 1985. Highlights of Dr. Halpert’s CYP2B research include the first identification of a specific amino acid adduct of a reactive intermediate and a mammalian protein, first elucidation of the isoform selectivity of a P450 inhibitor in any species, identification of P450 enzymes responsible for species differences in elimination of certain hexachlorobiphenyls, and the first x-ray crystal structures of human CYP2B6, rabbit CYP2B4 (including covalent complexes), and woodrat CYP2B35 and 2B37. Recent work has utilized X-ray crystallography, isothermal titration calorimetry, and hydrogen-deuterium exchange mass spectrometry to elucidate the role of enzyme plasticity in substrate recognition and binding and has revealed how CYP2B6 can bind compounds that vary almost 10-fold in molecular weight with comparable affinity.
In parallel with the structure-function studies of CYP2B enzymes, Dr. Halpert’s group has used a variety of solution biophysical approaches including pressure-perturbation spectroscopy, fluorescence resonance energy transfer, and absorbance spectroscopy to establish the role of multiple ligand binding and protein-protein interactions in allostery of the major human drug metabolizing enzyme, CYP3A4. This work helps explain the complexity of drug interactions involving CYP3A4 and has been supported by a MERIT Award from the National Institute of General Medical Sciences (NIGMS). Over the course of his career, Dr. Halpert has obtained extramural funding of >$30M in total costs. He is the author of 197 peer-reviewed publications and 19 invited reviews, with an H-index of 58 (as J. Halpert or J.R. Halpert) and 12,460 citations. He has also delivered invited lectures at >50 major national and international meetings. In 2006, Dr. Halpert was named a Fellow of the American Association for the Advancement of Science. In 2010, he was the recipient of the Bernard B. Brodie Award from the American Society for Pharmacology and Experimental Therapeutics (ASPET). On top of his extensive administrative responsibilities, Dr. Halpert maintains a laboratory funded by grants from NIEHS and the National Science Foundation. His group’s latest findings indicate an important role for halogen bonds in drug binding to cytochromes P450, which may contribute to the frequency of chlorinated compounds among drugs that survive the development process.
In addition to his university leadership positions, Dr. Halpert has been very active in professional service. Highlights include: member of the NIH Pharmacology Study Section (1992-1995) and Chairman (1993-1995); Member, NIGMS Biomedical Research and Research Training Review Committee (2000-2003); Editor for Drug Metabolism and Disposition (2000-2005); Secretary-Treasurer (including elect and past) of ASPET (2003-2006) and President (including elect and past) of ASPET (2009-2012); member of the International Advisory Committee for the fourteenth – twentieth Symposia on Microsomes and Drug Oxidations. Dr. Halpert currently serves as Treasurer Elect of the International Society for the Study of Xenobiotics. He has enjoyed strong working relationships, and in many cases financial support for research and/or training, with numerous pharmaceutical companies including Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Johnson & Johnson, Merck, and Pfizer. He has trained 10 Ph.D. students, >30 post-doctoral fellows, and 10 research track faculty. Six of his former trainees hold tenure-track or tenured faculty positions in pharmacology and toxicology, pharmaceutical sciences, or medicinal chemistry. Other former associates hold or have held scientist, senior scientist, or director positions at AbbVie, Allergan, AstraZeneca, Celgene, Merck, Pfizer, Pharmacia, Procter & Gamble, Sanofi, and Takeda. Dr. Halpert is currently working with three major pharmaceutical companies in Connecticut to secure internship positions for Pharm.D. students and to develop training programs directed to B.S. and M.S. level staff at the companies.