Biography
Dr. Daniel J. Rader is an Associate Professor of Medicine and Pathology at the University of Pennsylvania School of Medicine in Philadelphia, Pennsylvania. He is Director of Preventive Cardiology and the Lipid Clinic and Associate Director of the General Clinical Research Center. Dr. Rader runs a basic research laboratory focused on genetic regulation of lipoprotein metabolism and atherosclerosis and directs a clinical research program focused on human genetics of lipid disorders and atherosclerosis, imaging of atherosclerosis, and novel approaches to treatment of dyslipidemia and regression of atherosclerosis. He has a particular interest in HDL metabolism, factors and genes involved in its regulation, the nature of the relationship of HDL metabolism to atherosclerosis, and novel approaches to raising HDL cholesterol levels as a tool for treating and preventing atherosclerosis. Dr. Rader is a member of the American Society of Clinical Investigation and serves on the executive committee of the Arteriosclerosis, Thrombosis and Vascular Biology Council of the American Heart Association and the scientific board of the Sarnoff Foundation. He is an Established Investigator of the American Heart Association and a recipient of the Burroughs Wellcome Trust Clinician-Scientist Award in Translational Research.
Dr. Rader received his MD from the Medical College of Pennsylvania in Philadelphia, Pennsylvania. He then completed an internship and residency in internal medicine at Yale-New Haven Hospital in New Haven, Connecticut and was a Chief Resident in internal medicine at Yale. Dr Rader then did a fellowship at the Molecular Disease Branch of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health in Bethesda, Maryland, where he subsequently was appointed staff scientist. He was recruited to the University of Pennsylvania in 1994.
Dr. Rader is on the editorial boards of Arteriosclerosis Thrombosis and Vascular Biology, American Journal of Physiology (Endocrinology and Metabolism), Circulation, Circulation Research, and Trends in Molecular Medicine and is a reviewer for many journals, including Nature, Nature Medicine, Science, New England Journal of Medicine, and Journal of Clinical Investigation. Dr. Rader has authored over 120 peer-reviewed publications as well as many reviews and book chapters. He has written the chapters on lipid disorders and management for several textbooks including Kelley's Textbook of Internal Medicine, Topol's Textbook of Cardiovascular Medicine, and Nelson's Textbook of Pediatrics. He is a frequently invited speaker nationally and internationally on his basic and clinical research in lipoprotein metabolism, atherosclerosis, genetics, and gene therapy and on clinical topics such as novel approaches to cardiovascular risk assessment and management of lipid disorders.
Abstract
Genetics of Lipid Metabolism and Atherosclerosis
Atherosclerotic cardiovascular disease (ASCVD) remains epidemic in the U.S. and most of the world. Effective prevention requires accurate identification of those at risk and institution of therapies that reduce risk. Stabilization and regression of atherosclerosis require development of new therapeutic interventions that are effective and complement existing therapies. A better understanding of the genetics of atherosclerosis and its risk factors will provide greater ability to predict future risk as well as lead to new targets for therapeutic intervention. Plasma lipoprotein metabolism is intimately related to the development of atherosclerosis. Plasma low-density lipoprotein (LDL) cholesterol is directly associated and plasma high-density (HDL) cholesterol inversely associated with ASCVD. Reduction of LDL-C is proven to reduce risk although only by about one-third over 5 years. The effects of raising HDL-C are uncertain as highly effective HDL-raising interventions are not yet available. Our broad goal is to investigate the role of genetic variation in determining levels of LDL-C and HDL-C and translate those findings into new abilities to predict, prevent, and regress atherosclerosis.
Specific Aims:
- Determine the safety and efficacy of pharmacologic inhibiton of the microsomal transfer protein (MTP) in patients with homozygous FH. Investigate the effects of MTP inhibition in homozygous FH patients on in vivo lipoprotein metabolism and atherosclerosis.
- Investigate the molecular etiology of dominantly-inherited high HDL cholesterol using both linkage analysis and candidate gene approaches.
- Develop methods for quantitation of peripheral cholesterol mobilization and reverse cholesterol transport in humans and apply them to the investigation of existing and novel therapeutic approaches targeted toward HDL metabolism.
These studies work toward an era in which genetics will allow us to identify high-risk individuals well before their clinical event and to design new therapies that will allow us to effectively prevent and regress atherosclerosis.