Brown, Michael S.

▪ American geneticist

in full  Michael Stuart Brown  

born April 13, 1941, New York, N.Y., U.S.

      American molecular geneticist who, along with Joseph L. Goldstein (Goldstein, Joseph L.), was awarded the 1985 Nobel Prize for Physiology or Medicine for their elucidation of a key link in the metabolism of cholesterol in the human body.

      Brown graduated from the University of Pennsylvania, Philadelphia, in 1962 and received his M.D. from that university's medical school in 1966. He became friends with Goldstein when they were both working as interns at Massachusetts General Hospital in Boston during 1966–68. After conducting research at the National Institutes of Health from 1968 to 1971, he became an assistant professor at the Southwestern Medical School in Dallas, Texas, where he was reunited with his colleague Goldstein.

      In Dallas the two men began their collaborative research on the genetic factors that are responsible for high levels of cholesterol in the bloodstream. They compared the cells of normal persons with those of persons having familial hypercholesterolemia, which is an inherited tendency to get abnormally high blood cholesterol levels and, as a result, atherosclerosis and other circulatory ailments.

      Brown and Goldstein were able to trace a genetic defect in the afflicted persons that resulted in their lacking or being deficient in cell receptors for low-density lipoproteins (LDL), which are the primary cholesterol carrying particles. Their research established that these cell receptors draw the LDL particles into the cells as a prelude to breaking them down, and thus remove them from the bloodstream. The two men also discovered that the cell capture of such lipoproteins inhibits the further production of new LDL receptors by the cells, thus explaining how high-cholesterol diets overwhelm the body's natural capacity for withdrawing cholesterol from the bloodstream.

      Brown later collaborated with Goldstein in research to develop new drugs effective in lowering blood cholesterol levels and in researching the basic genetic code behind the LDL receptor. From 1977 he was professor and director of the Center for Genetic Diseases at the Southwestern Medical School, where in 1985 he was elevated to regental professor. In 1984 Brown and Goldstein were awarded the Louisa Gross Horowitz Prize for Biology or Biochemistry, and in 1988 Brown was awarded the National Medal of Science.

      In the 1990s Brown and Goldstein discovered sterol regulatory element binding proteins (SREBPs), transcription factors that control the uptake and synthesis of cholesterol and fatty acids. In their follow-up studies they uncovered the mechanism by which SREBPs are activated to regulate the metabolism of lipids. In 2003 they were awarded the Albany Medical Prize. Brown and Goldstein shared a laboratory, where they conducted their research jointly.

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