Jere P. Segrest, MD, PhD
Professor of Medicine
In the early 1970s, the structures of membranes and lipoproteins were a great mystery; the generally accepted models varied from unlikely to impossible. As a Staff Associate at NIH, Dr. Segrest played a major role in the revolution that solved the mystery when he published two seminal papers demonstrating, for the first time, the basic structural principles underlying the supramolecular assembly of proteins and lipids in membranes—the transmembrane hydrophobic alpha-helix—and in lipoproteins, the surface-associating amphipathic alpha-helix. At the University of Alabama, Birmingham, he focused the bulk of his research on the role of the amphipathic alpha-helix in plasma lipoproteins. Since 1974 he has been the PI on a total of ten separate R01 grants, a NHLBI shared facility grant, and a program project that was funded to its 25th year. Lipid exchange and particle remodeling are critically important processes during metabolism of HDL particles at every step in the antiatherogenic process of reverse cholesterol transport. Because HDL is a soft form of condensed matter easily deformable by thermal fluctuations, the mechanisms for HDL dynamics and remodeling are not well understood. Recently, Segrest took the high-risk approach of using a computational approach—molecular dynamics (MD) simulations—to aid in exploring the dynamic structure of both discoidal and spheroidal (circulating) HDL. In spite of the high risk, he has published thirteen high-impact papers that, for the first time, provide a robust model of HDL structure at the all atom level.