The Brown/Goldstein laboratory is unique in medical research because it has been supervised jointly by two scientists for 33 years. The laboratory is devoted to solving a fundamental problem: how do animals regulate the synthesis of cholesterol and other lipids so as to maintain constant membrane composition? Several years ago we discovered sterol regulatory element-binding proteins (SREBPs), membrane-bound transcription factors that activate genes encoding more than 30 enzymes required for lipid synthesis, uptake and storage. To reach the nucleus the SREBPs must travel to the Golgi complex where proteases release the active transcription domains. We call this the SREBP pathway. Excess cholesterol blocks SREBP movement, thus inhibiting lipid synthesis and establishing a feedback loop. Defects in SREBP regulation contribute to common diseases, ranging from heart attacks to obesity and diabetes.
RESEARCH INTERESTS
Cholesterol and Lipoprotein Metabolism
Genetics of Human Disease
RECENT PUBLICATIONS
Gong, Y., Lee, J.N., Brown, M.S., Goldstein, J.L. and Ye, J., "Juxtamembranous aspartic acid in Insig-1 and Insig-2 is required for regulating cholesterol homeostasis." Proc. Natl. Acad. Sci. USA, 103:6154-6159, 2006
Brown, M.S. and Goldstein, J.L., "Lowering LDL ? not only how low, but how long?" Science, 311:1721-1723, 2006
Engelking, L.J., Evers, B.M., Richardson, J.A., Goldstein, J.L., Brown, M.S. and Liang, G., "Severe facial clefting in Insig-deficient mouse embryos caused by sterol accumulation and reversed by lovastatin." J. Clin. Invest., 116:2356-2365, 2006
Radhakrishnan, A., Ikeda, Y., Kwon, H.J., Brown, M.S., and Goldstein, J.L., "Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Oxysterols block transport by binding to Insig." Proc. Natl. Acad. Sci. USA, 104:6511-6518, 2007
Sun, L.-P., Seemann, J., Goldstein, J.L., and Brown, M.S., "Sterol-regulated transport of SREBPS from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteins." Proc. Natl. Acad. Sci. USA, 104:6519-6526, 2007
SIGNIFICANT PUBLICATIONS
Goldstein, J.L. and Brown, M.S., "Familial hypercholesterolemia: Identification of a defect in the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity associated with overproduction of cholesterol" PNAS USA, 70:2804-2808, 1973
Goldstein, J.L, Anderson, R.G.W., and Brown, M.S., "Coated pits, coated vesicles, and receptor-mediated endocytosis" Nature, 279:679-685, 1979
Brown, M.S. and Goldstein, J.L., "A receptor-mediated pathway for cholesterol homeostasis" Science, 232:34-47, 1986
Goldstein, J.L. and Brown, M.S., "Regulation of the mevalonate pathway" Nature, 343:425-430, 1990
Goldstein, J.L. and Brown, M.S., "The Cholesterol Quartet" Science, 232:1310-1312, 2001
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