Chief, Molecular Disease Branch
National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)

Dr. H. Bryan Brewer, Jr., received his undergraduate degree from Johns Hopkins University and medical degree from Stanford University School of Medicine. After completing his internship and residency in internal medicine at the Massachusetts General Hospital, he joined the National Heart, Lung, and Blood Institute of the National Institutes of Health as a clinical associate. Dr. Brewer was promoted to Head of the Peptide Chemistry Section in the Molecular Disease Branch and then, to Chief of the Molecular Disease Branch of the National Heart, Lung, and Blood Institute, a position he has held since 1976.

Dr. Brewer's research led to the elucidation of the first published sequences for the human plasma apolipoproteins, the initial determination of the metabolism of the plasma apolipoproteins in normal and hyperlipidemic individuals, as well as the identification of multiple gene defects leading to the genetic dyslipoproteinemias. More recently, he has pioneered the use of transgenic mice and rabbits, as well as recombinant adenovirus vectors to identify genes that modulate lipoprotein metabolism and the development of atherosclerosis.

Dr. Brewer has been the recipient of the JD Lane Investigator Award from the Public Health Service, the Heinrich Wieland Prize from the Federal Republic of Germany, and the Public Health Service Commendation, Meritorious Service and Distinguished Service Medals from the National Institutes of Health. He has served as a member of the Board of the National Cholesterol Education Program, which established treatment guidelines for patients with hyperlipidemia in the United States. He has published more than 300 original reports, and 70 reviews and book chapters, on the subjects of genetic dyslipoproteinemias, lipoprotein metabolism, and atherosclerosis.

Targeting atherosclerosis with drug-modulated gene therapy and other approaches

HDL, the major anti-atherogenic plasma lipoprotein, plays a major role in cholesterol metabolism and the prevention of atherosclerosis. Lecithin:cholesterol acyltransferase (LCAT) esterifies free cholesterol that is present in circulating plasma lipoproteins, and modulates the plasma concentrations of HDL. Overexpression of human LCAT in transgenic rabbits leads to significant reductions in the development of diet-induced, aortic lesions.

Thus, LCAT has been identified as a potential candidate gene that may modulate not only the metabolism of plasma lipoproteins but also the development of atherosclerosis. The use of pharmacologic and/or gene therapy approaches to increase plasma LCAT concentration for the treatment of atherosclerosis is being evaluated.