Michael Stuart Brown ForMemRS NAS AAA&S APS (born April 13, 1941) is an American geneticist and Nobel laureate. He was awarded the Nobel Prize in Physiology or Medicine with Joseph L. Goldstein in 1985 for describing the regulation of cholesterol metabolism.

Early life and education

Brown was born in Brooklyn, New York, on April 13, 1941, the son of Evelyn, a homemaker, and Harvey Brown, a textile salesman. His family is Jewish. He graduated from Cheltenham High School in Wyncote, Pennsylvania. Brown graduated from the University of Pennsylvania in 1962 and received his M.D. from the University of Pennsylvania School of Medicine in 1966.[citation needed]

Career

Moving to the University of Texas Health Science Center in Dallas, now the UT Southwestern Medical Center, Brown and colleague Joseph L. Goldstein researched cholesterol metabolism and discovered that human cells have low-density lipoprotein (LDL) receptors that extract cholesterol from the bloodstream. The lack of sufficient LDL receptors is implicated in familial hypercholesterolemia, which predisposes heavily for cholesterol-related diseases. In addition to explaining the underlying pathology of this disease, their work uncovered a fundamental aspect of cell biology - receptor-mediated endocytosis. Their findings led to the development of statin drugs, the cholesterol-lowering compounds that today are used by 16 million Americans and are the most widely prescribed medications in the United States.[citation needed] Their discoveries are improving more lives every year, both in the US and around the world.[citation needed] New federal cholesterol guidelines will triple the number of Americans taking statin drugs to lower their cholesterol, reducing the risk of heart disease and stroke for countless people. Following these important advances, their team of dedicated researchers elucidated the role of lipid modification of proteins (protein prenylation) in cancer. In 1984 he was awarded the Louisa Gross Horwitz Prize from Columbia University together with Joseph L. Goldstein (co-recipient of 1985 Nobel Prize in Physiology or Medicine). In 1988, Brown received the National Medal of Science for his contributions to medicine.

In 1993, their trainees Xiaodong Wang and Michael Briggs purified the sterol regulatory element binding proteins (SREBPs). Since 1993, Brown, Goldstein, and their colleagues have described the unexpectedly complex machinery by which cells maintain the necessary levels of fats and cholesterol in the face of varying environmental circumstances.

Brown holds the W. A. (Monty) Moncrief Distinguished Chair in Cholesterol and Arteriosclerosis Research; is a Regental Professor of the University of Texas; holds the Paul J. Thomas Chair in Medicine.[citation needed]

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Awards and honors

Brown has won numerous awards and honors, including:

Bibliography

  • Brown MS, Goldstein JL (Jul 1974). "Expression of the familial hypercholesterolemia gene in heterozygotes: mechanism for a dominant disorder in man". Science. 185 (4145): 61–3. Bibcode:. doi:. PMID . S2CID .
  • Brown MS, Goldstein JL (Nov 1975). "Regulation of the activity of the low density lipoprotein receptor in human fibroblasts". Cell. 6 (3): 307–16. doi:. PMID . S2CID .
  • Goldstein JL, Basu SK, Brunschede GY, Brown MS (Jan 1976). "Release of low density lipoprotein from its cell surface receptor by sulfated glycosaminoglycans". Cell. 7 (1): 85–95. doi:. PMID . S2CID .
  • Brown MS, Goldstein JL (Jan 1976). "Receptor-mediated control of cholesterol metabolism". Science. 191 (4223): 150–4. Bibcode:. doi:. PMID .
  • Goldstein JL, Sobhani MK, Faust JR, Brown MS (Oct 1976). "Heterozygous familial hypercholesterolemia: failure of normal allele to compensate for mutant allele at a regulated genetic locus". Cell. 9 (2): 195–203. doi:. PMID . S2CID .
  • Brown MS, Goldstein JL (Dec 1976). "Analysis of a mutant strain of human fibroblasts with a defect in the internalization of receptor-bound low density lipoprotein". Cell. 9 (4 PT 2): 663–74. doi:. PMID . S2CID .
  • Anderson RG, Brown MS, Goldstein JL (Mar 1977). "Role of the coated endocytic vesicle in the uptake of receptor-bound low density lipoprotein in human fibroblasts". Cell. 10 (3): 351–64. doi:. PMID . S2CID .
  • Goldstein JL, Brown MS, Stone NJ (Nov 1977). "Genetics of the LDL receptor: evidence that the mutations affecting binding and internalization are allelic". Cell. 12 (3): 629–41. doi:. PMID . S2CID .
  • Anderson RG, Goldstein JL, Brown MS (1977). "A mutation that impairs the ability of lipoprotein receptors to localise in coated pits on the cell surface of human fibroblasts". Nature. 270 (5639): 695–9. Bibcode:. doi:. PMID . S2CID .
  • Anderson RG, Vasile E, Mello RJ, Brown MS, Goldstein JL (Nov 1978). "Immunocytochemical visualization of coated pits and vesicles in human fibroblasts: relation to low density lipoprotein receptor distribution". Cell. 15 (3): 919–33. doi:. PMID . S2CID .
  • Goldstein JL, Anderson RG, Brown MS (Jun 1979). "Coated pits, coated vesicles, and receptor-mediated endocytosis". Nature. 279 (5715): 679–85. Bibcode:. doi:. PMID . S2CID .
  • Mello RJ, Brown MS, Goldstein JL, Anderson RG (Jul 1980). "LDL receptors in coated vesicles isolated from bovine adrenal cortex: binding sites unmasked by detergent treatment". Cell. 20 (3): 829–37. doi:. PMID . S2CID .
  • Brown MS, Kovanen PT, Goldstein JL (May 1981). "Regulation of plasma cholesterol by lipoprotein receptors". Science. 212 (4495): 628–35. Bibcode:. doi:. PMID .
  • Basu SK, Goldstein JL, Anderson RG, Brown MS (May 1981). "Monensin interrupts the recycling of low density lipoprotein receptors in human fibroblasts". Cell. 24 (2): 493–502. doi:. PMID . S2CID .
  • Tolleshaug H, Goldstein JL, Schneider WJ, Brown MS (Oct 1982). "Posttranslational processing of the LDL receptor and its genetic disruption in familial hypercholesterolemia". Cell. 30 (3): 715–24. doi:. PMID . S2CID .
  • Basu SK, Goldstein JL, Brown MS (Feb 1983). "Independent pathways for secretion of cholesterol and apolipoprotein E by macrophages". Science. 219 (4586): 871–3. Bibcode:. doi:. PMID .
  • Brown MS, Anderson RG, Goldstein JL (Mar 1983). "Recycling receptors: the round-trip itinerary of migrant membrane proteins". Cell. 32 (3): 663–7. doi:. PMID . S2CID .
  • Tolleshaug H, Hobgood KK, Brown MS, Goldstein JL (Mar 1983). "The LDL receptor locus in familial hypercholesterolemia: multiple mutations disrupt transport and processing of a membrane receptor". Cell. 32 (3): 941–51. doi:. PMID . S2CID .
  • Larkin JM, Brown MS, Goldstein JL, Anderson RG (May 1983). "Depletion of intracellular potassium arrests coated pit formation and receptor-mediated endocytosis in fibroblasts". Cell. 33 (1): 273–85. doi:. PMID . S2CID .
  • Orci L, Brown MS, Goldstein JL, Garcia-Segura LM, Anderson RG (Apr 1984). "Increase in membrane cholesterol: a possible trigger for degradation of HMG CoA reductase and crystalloid endoplasmic reticulum in UT-1 cells". Cell. 36 (4): 835–45. doi:. PMID . S2CID .
  • Chin DJ, Gil G, Russell DW, et al. (1984). "Nucleotide sequence of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, a glycoprotein of endoplasmic reticulum". Nature. 308 (5960): 613–7. Bibcode:. doi:. PMID . S2CID .
  • Russell DW, Schneider WJ, Yamamoto T, Luskey KL, Brown MS, Goldstein JL (Jun 1984). "Domain map of the LDL receptor: sequence homology with the epidermal growth factor precursor". Cell. 37 (2): 577–85. doi:. PMID . S2CID .
  • Reynolds GA, Basu SK, Osborne TF, et al. (Aug 1984). "HMG CoA reductase: a negatively regulated gene with unusual promoter and 5' untranslated regions". Cell. 38 (1): 275–85. doi:. PMID . S2CID .
  • Yamamoto T, Davis CG, Brown MS, et al. (Nov 1984). "The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA". Cell. 39 (1): 27–38. doi:. PMID . S2CID .
  • Lehrman MA, Schneider WJ, Südhof TC, Brown MS, Goldstein JL, Russell DW (Jan 1985). . Science. 227 (4683): 140–6. Bibcode:. doi:. PMC . PMID .
  • Südhof TC, Goldstein JL, Brown MS, Russell DW (May 1985). . Science. 228 (4701): 815–22. Bibcode:. doi:. PMC . PMID .
  • Südhof TC, Russell DW, Goldstein JL, Brown MS, Sanchez-Pescador R, Bell GI (May 1985). "Cassette of eight exons shared by genes for LDL receptor and EGF precursor". Science. 228 (4701): 893–5. Bibcode:. doi:. PMID .
  • Gil G, Faust JR, Chin DJ, Goldstein JL, Brown MS (May 1985). "Membrane-bound domain of HMG CoA reductase is required for sterol-enhanced degradation of the enzyme". Cell. 41 (1): 249–58. doi:. PMID . S2CID .
  • Lehrman MA, Goldstein JL, Brown MS, Russell DW, Schneider WJ (Jul 1985). "Internalization-defective LDL receptors produced by genes with nonsense and frameshift mutations that truncate the cytoplasmic domain". Cell. 41 (3): 735–43. doi:. PMID . S2CID .
  • Osborne TF, Goldstein JL, Brown MS (Aug 1985). "5' end of HMG CoA reductase gene contains sequences responsible for cholesterol-mediated inhibition of transcription". Cell. 42 (1): 203–12. doi:. PMID . S2CID .
  • Brown MS, Goldstein JL (1985). "Scavenger cell receptor shared". Nature. 316 (6030): 680–1. doi:. PMID . S2CID .
  • Brown MS, Goldstein JL (Apr 1986). "A receptor-mediated pathway for cholesterol homeostasis". Science. 232 (4746): 34–47. Bibcode:. doi:. PMID .
  • Davis CG, Lehrman MA, Russell DW, Anderson RG, Brown MS, Goldstein JL (Apr 1986). "The J.D. mutation in familial hypercholesterolemia: amino acid substitution in cytoplasmic domain impedes internalization of LDL receptors". Cell. 45 (1): 15–24. doi:. PMID . S2CID .
  • Yamamoto T, Bishop RW, Brown MS, Goldstein JL, Russell DW (Jun 1986). . Science. 232 (4755): 1230–7. Bibcode:. doi:. PMC . PMID .
  • Lehrman MA, Goldstein JL, Russell DW, Brown MS (Mar 1987). "Duplication of seven exons in LDL receptor gene caused by Alu-Alu recombination in a subject with familial hypercholesterolemia". Cell. 48 (5): 827–35. doi:. PMID . S2CID .
  • Südhof TC, Russell DW, Brown MS, Goldstein JL (Mar 1987). "42 bp element from LDL receptor gene confers end-product repression by sterols when inserted into viral TK promoter". Cell. 48 (6): 1061–9. doi:. PMID . S2CID .
  • Davis CG, Goldstein JL, Südhof TC, Anderson RG, Russell DW, Brown MS (1987). "Acid-dependent ligand dissociation and recycling of LDL receptor mediated by growth factor homology region". Nature. 326 (6115): 760–5. Bibcode:. doi:. PMID . S2CID .
  • Hofmann SL, Russell DW, Brown MS, Goldstein JL, Hammer RE (Mar 1988). "Overexpression of low density lipoprotein (LDL) receptor eliminates LDL from plasma in transgenic mice". Science. 239 (4845): 1277–81. Bibcode:. doi:. PMID .
  • Reiss Y, Goldstein JL, Seabra MC, Casey PJ, Brown MS (Jul 1990). "Inhibition of purified p21ras farnesyl:protein transferase by Cys-AAX tetrapeptides". Cell. 62 (1): 81–8. doi:. PMID . S2CID .
  • Yokode M, Hammer RE, Ishibashi S, Brown MS, Goldstein JL (Nov 1990). "Diet-induced hypercholesterolemia in mice: prevention by overexpression of LDL receptors". Science. 250 (4985): 1273–5. Bibcode:. doi:. PMID .
  • Seabra MC, Reiss Y, Casey PJ, Brown MS, Goldstein JL (May 1991). "Protein farnesyltransferase and geranylgeranyltransferase share a common alpha subunit". Cell. 65 (3): 429–34. doi:. PMID . S2CID .
  • Chen WJ, Andres DA, Goldstein JL, Russell DW, Brown MS (Jul 1991). "cDNA cloning and expression of the peptide-binding beta subunit of rat p21ras farnesyltransferase, the counterpart of yeast DPR1/RAM1". Cell. 66 (2): 327–34. doi:. PMID . S2CID .
  • Seabra MC, Brown MS, Slaughter CA, Südhof TC, Goldstein JL (Sep 1992). "Purification of component A of Rab geranylgeranyl transferase: possible identity with the choroideremia gene product". Cell. 70 (6): 1049–57. doi:. PMID . S2CID .
  • Brown MS, Goldstein JL (Oct 1992). "Koch's postulates for cholesterol". Cell. 71 (2): 187–8. doi:. PMID . S2CID .
  • Andres DA, Seabra MC, Brown MS, et al. (Jun 1993). "cDNA cloning of component A of Rab geranylgeranyl transferase and demonstration of its role as a Rab escort protein". Cell. 73 (6): 1091–9. doi:. PMID . S2CID .
  • Yokoyama C, Wang X, Briggs MR, et al. (Oct 1993). "SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene". Cell. 75 (1): 187–97. doi:. PMID . S2CID .
  • Garcia CK, Goldstein JL, Pathak RK, Anderson RG, Brown MS (Mar 1994). "Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle". Cell. 76 (5): 865–73. doi:. PMID . S2CID .
  • Wang X, Sato R, Brown MS, Hua X, Goldstein JL (Apr 1994). "SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis". Cell. 77 (1): 53–62. doi:. PMID . S2CID .
  • Sakai J, Duncan EA, Rawson RB, Hua X, Brown MS, Goldstein JL (Jun 1996). . Cell. 85 (7): 1037–46. doi:. PMID . S2CID .
  • Hua X, Nohturfft A, Goldstein JL, Brown MS (Nov 1996). . Cell. 87 (3): 415–26. doi:. PMID . S2CID .
  • Brown MS, Goldstein JL (May 1997). . Cell. 89 (3): 331–40. doi:. PMID . S2CID .
  • DeBose-Boyd RA, Brown MS, Li WP, Nohturfft A, Goldstein JL, Espenshade PJ (Dec 1999). . Cell. 99 (7): 703–12. doi:. PMID .
  • Brown MS, Ye J, Rawson RB, Goldstein JL (Feb 2000). . Cell. 100 (4): 391–8. doi:. PMID . S2CID .
  • Nohturfft A, Yabe D, Goldstein JL, Brown MS, Espenshade PJ (Aug 2000). . Cell. 102 (3): 315–23. doi:. PMID . S2CID .
  • Yang T, Espenshade PJ, Wright ME, et al. (Aug 2002). . Cell. 110 (4): 489–500. doi:. PMID . S2CID .

See also

External links

  • on Nobelprize.org