2015 HARVARD CATALYST
PROGRAM FOR FACULTY DEVELOPMENT AND DIVERSITY INCLUSION (PFDD)
FACULTY FELLOWSHIP - BWH
Kathryn T. Hall, PhD, MPH, MA
Assistant Professor in Medicine, Division of Preventive Medicine,
Brigham and Women's Hospital and Harvard Medical School
Mentor: Kenneth J. Mukamal, MD, MPH, MA, Associate Professor of Medicine, Harvard Medical School; Associate Physician, Department of Medicine, Beth Israel Deaconess Medical Center
Division Chief: JoAnn Manson, MD, DrPH, Professor of Medicine and Elizabeth Fay Brigham Professor of Women's Health at Harvard Medical School, and Chief of the Division of Preventive Medicine and Co-Director of the Connors Center for Women's Health and Gender Biology at Brigham and Women's Hospital in Boston
Project Title: “Epidemiological, Pharmacogenomic and Clinical Impact of Catechol-O-Methyltransferase on Cardiovascular Disease”
Project Description: This study is designed to determine if genetic variation in catechol-O-methyltransferase (COMT), a key enzyme in catecholamine metabolism, modifies incidence of cardiovascular disease (CVD) and aspirin treatment effects in men and racial/ethnic minority populations. Despite significant strides in prevention, CVD remains a leading cause of death. Pharmacogenomics, the study of genetic effects on drug response, has expanded understanding of CVD pathophysiology and, at least for specific genes and drugs, raised the possibility of personalized medicine. However, the potential of pharmacogenomics to guide improvements in personalized treatment remains largely unrealized. In particular, the impact of gene interactions with commonly used drugs is difficult to assess in epidemiologic studies and clinical trials. This is partly due to extraordinarily large sample sizes required for genome-wide studies of gene-drug interactions and lack of strong candidate genes. We recently identified COMT as a gene with plausible physiological links to both CVD and drug metabolism. In the Women’s Health Study (WHS), a placebo-controlled trial of aspirin for CVD prevention in predominantly Caucasian women, we showed that highly prevalent COMT variants were associated with incidence of major CVD. Importantly, we showed that COMT-associated CVD 3 protection was eliminated in women randomized to aspirin. Given widespread use of aspirin and evidence that COMT-drug sensitive alleles are more prevalent in minority populations, investigating this pharmacogenetic locus in male and minority racial/ethnic populations is imperative. Here I propose to use genetic data from a multiethnic longitudinal cohort and a clinical study to elucidate the generalizability and underlying mechanisms of COMT-CVD associations.
Biography: Dr. Kathryn T. Hall received her PhD in Microbiology and Molecular Genetics from Harvard University in 1996. During her post-doctoral fellowship with Dr. Lee Nadler at Dana Farber Cancer Institute, she cloned and characterized CD100, the first semaphorin identified in the immune system. For the next 10 years, Dr. Hall tackled problems in biotech research and developed expertise in pharmaceutical drug development, first at Wyeth and then at Millennium Pharmaceuticals, where she became an Associate Director of Drug Development. While working in the pharmaceutical industry, Dr. Hall was struck by the health disparities in access to drugs and the tremendous variability in the responses of those who did receive treatment. To address these issues she developed public health media messages acquiring a Masters in Visual Media Arts from Emerson College. With the goal of continuing to examine and address these issues through academic biomedical research, Dr. Hall returned to Harvard Medical School in 2010, joining the Fellowship in Integrative Medicine at Beth Israel Deaconess Medical Center (BIDMC) in 2012 and receiving a Master’s in Public Health from Harvard School of Public Health in 2014.
Working with Ted Kaptchuk at BIDMC in the Program in Placebo Studies, Dr. Hall focused on catechol-O-methyltransferase (COMT) an enzyme that metabolizes catecholamines such as dopamine and epinephrine and has pleiotropic effects in a broad set of diseases and treatments. Her groundbreaking paper identifying COMT as the first genetic marker of placebo response was published in PLOS ONE and has been cited over 50 times since 2012. Dr. Hall coined the term “placebome” to describe the potential genomic perturbations that influence the placebo response and her review of the evidence and implications of its impact on the placebo response is in press at Trends in Molecular Medicine. Dr. Hall’s research captured media attention and her research has been the focus of numerous articles including features in Science and Discover magazine.
Dr. Hall’s current research builds on the emerging role of COMT in network medicine as a hub influencing disease and treatment outcomes from cardiovascular disease to cancer. Using data from the Women’s Health Study (WHS), a large placebo-controlled randomized clinical trial of aspirin for the prevention of cardiovascular disease, Dr. Hall working with Dr. Daniel Chasman at Brigham and Women’s Hospital made the novel observation that women homozygous for the low-activity form of the COMT enzyme had lower rates of major cardiovascular disease when randomized to aspirin compared to placebo; in contrast high-activity COMT homozygotes had increased rates of cardiovascular disease when randomized to aspirin compared to placebo. These original findings have important implications for personalized medicine and were recently published in Arteriosclerosis, Thrombosis and Vascular Biology, 2014. Currently with Dr. Kenneth Mukamal at BIDMC, Dr. Hall is examining COMT in diabetes and cancer. Dr. Hall will complete the Integrative Fellowship later this year and will join the Harvard Medical School faculty in August 2015.