GOLDSTEIN, JOSEPH LEONARD

GOLDSTEIN, JOSEPH LEONARD (1940– ), U.S. medical geneticist and Nobel laureate. Goldstein was born in Sumter, South Carolina, and graduated with a B.S. in chemistry from Washington and Lee University in Lexington, Virginia (1962), and an M.D. from the University of Texas Southwestern Medical School at Dallas (1966). After medical training at Massachusetts General Hospital, Boston (1966–68), where he   met his long-term collaborator michael brown , he began his research career at the National Institutes of Health, Bethesda (1968–70). He worked in the laboratory of Marshall Nirenberg and with Donald Fredrickson, clinical director of the National Heart Institute (1968–70) whose patients with lipid disorders stimulated his interest in cholesterol metabolism. His genetic studies with Arno Motulsky at the University of Washington, Seattle (1970–72) clarified the link between inherited abnormalities of lipid metabolism, especially high blood cholesterol levels, and susceptibility to heart disease. He also learned techniques for culturing readily accessible cells called fibroblasts which he subsequently used to study normal and abnormal lipid metabolism. In 1972 he joined the faculty of the Southwestern Medical School, Dallas, initially as head of the division of medical genetics, progressing to professor (1974) and Paul J. Thomas Professor of Medicine and Genetics, chairman of the department of medical genetics from 1977, and regent professor of the University of Texas (1985). He continued his collaboration with Michael Brown throughout this period in Dallas, and they shared the Nobel Prize for physiology or medicine (1985) for the research which identified the receptors on cell surfaces which normally regulate blood levels of low-density lipoproteins. They further showed that low density lipoproteins within cells control the enzyme coenzyme A reductase which governs cholesterol synthesis, especially by the liver. They characterized the genetic defects in these receptors which lead to high blood levels of low-density lipoproteins and cholesterol. This results in excessive lipid deposition in blood vessel walls predisposing to disease, especially in coronary arteries. These observations led to a greater understanding of the regulatory role of receptors in general. They also underlie the modern clinical practice of reducing abnormally high cholesterol levels by dietary means or drugs. His subsequent collaborative work with Michael Brown identified other metabolic defects resulting in high blood lipoprotein levels dependent upon high blood insulin levels and insulin resistance. His many honors include election to the U.S. National Academy of Sciences (1980), the Gairdner Award (1981), presidency of the American Society for Clinical Investigation (1985–86), and the Lasker Award in Basic Medical Science (1985). (Michael Denman (2nd ed.)