Michael Stuart Brown

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Michael Stuart Brown

Born April 13, 1941 (1941-04-13) (age 67)
Brooklyn, New York
Citizenship American
Nationality American
Ethnicity Caucasian
Fields Biology
Alma mater University of Pennsylvania
Known for Metabolizing cholesterol
Notable awards Nobel Prize in Physiology or Medicine
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Further information might be found on the talk page or at requests for expansion. (January 2007)
For other persons named Michael Stuart, see Michael Stuart (disambiguation).

Dr. Michael Stuart Brown (b. April 13, 1941 in Brooklyn, New York[1]) is a Nobel Prize winning American geneticist. He was awarded the Nobel Prize in Physiology or Medicine with Joseph L. Goldstein in 1985 for describing the regulation of cholesterol metabolism.

Contents

[edit] Biography

Dr. Brown graduated from the University of Pennsylvania in 1962 and received his M.D. from Penn medical school in 1966. Moving to the University of Texas Health Science Center in Dallas (now called 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. Their discoveries are improving more lives every year, both in the United States and around the world. 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 National Medal of Science for his contributions to the world of Medicine.

In 1993, their trainees Xiaodong Wang and Michael Briggs purified the Sterol regulatory element binding proteins (SREBPs). Since 1993, Drs. 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. Dr. Brown holds The W. A. (Monty) Moncrief Distinguished Chair in Cholesterol and Arteriosclerosis Research; is a Regental Professor of the University of Texas; and holds the Paul J. Thomas Chair in Medicine. Frequently mentioned as a candidate for nationally-prominent positions in scientific administration, Dr. Brown, like his colleague Joseph L. Goldstein, elects to continue hands-on involvement with research, leading a research team that typically includes a dozen doctoral and postdoctoral trainees. He and his colleague are among the most highly-cited scientists in the world.

[edit] External links

[edit] Key Papers

  • [1] Expression of the familial hypercholesterolemia gene in heterozygotes: mechanism for a dominant disorder in man. Science. 1974 Jul 5;185(4145):61-3.
  • [2] Regulation of the activity of the low density lipoprotein receptor in human fibroblasts. Cell. 1975 Nov;6(3):307-16.
  • [3] Release of low density lipoprotein from its cell surface receptor by sulfated glycosaminoglycans. Cell. 1976 Jan;7(1):85-95.
  • [4] Receptor-mediated control of cholesterol metabolism. Science. 1976 Jan 16;191(4223):150-4.
  • [5] Heterozygous familial hypercholesterolemia: failure of normal allele to compensate for mutant allele at a regulated genetic locus. Cell. 1976 Oct;9(2):195-203.
  • [6] Analysis of a mutant strain of human fibroblasts with a defect in the internalization of receptor-bound low density lipoprotein. Cell. 1976 Dec;9(4 PT 2):663-74.
  • [7] Role of the coated endocytic vesicle in the uptake of receptor-bound low density lipoprotein in human fibroblasts. Cell. 1977 Mar;10(3):351-64.
  • [8] Genetics of the LDL receptor: evidence that the mutations affecting binding and internalization are allelic. Cell. 1977 Nov;12(3):629-41.
  • [9] A mutation that impairs the ability of lipoprotein receptors to localise in coated pits on the cell surface of human fibroblasts. Nature. 1977 Dec 22-29;270(5639):695-9.
  • [10] Immunocytochemical visualization of coated pits and vesicles in human fibroblasts: relation to low density lipoprotein receptor distribution. Cell. 1978 Nov;15(3):919-33.
  • [11] Coated pits, coated vesicles, and receptor-mediated endocytosis. Nature. 1979 Jun 21;279(5715):679-85
  • [12] LDL receptors in coated vesicles isolated from bovine adrenal cortex: binding sites unmasked by detergent treatment. Cell. 1980 Jul;20(3):829-37.
  • [13] Regulation of plasma cholesterol by lipoprotein receptors. Science. 1981 May 8;212(4495):628-35.
  • [14] Monensin interrupts the recycling of low density lipoprotein receptors in human fibroblasts. Cell. 1981 May;24(2):493-502.
  • [15] Posttranslational processing of the LDL receptor and its genetic disruption in familial hypercholesterolemia. Cell. 1982 Oct;30(3):715-24
  • [16] Independent pathways for secretion of cholesterol and apolipoprotein E by macrophages. Science. 1983 Feb 18;219(4586):871-3.
  • [17] Recycling receptors: the round-trip itinerary of migrant membrane proteins. Cell. 1983 Mar;32(3):663-7
  • [18] The LDL receptor locus in familial hypercholesterolemia: multiple mutations disrupt transport and processing of a membrane receptor. Cell. 1983 Mar;32(3):941-51.
  • [19] Depletion of intracellular potassium arrests coated pit formation and receptor-mediated endocytosis in fibroblasts. Cell. 1983 May;33(1):273-85
  • [20] Increase in membrane cholesterol: a possible trigger for degradation of HMG CoA reductase and crystalloid endoplasmic reticulum in UT-1 cells. Cell. 1984 Apr;36(4):835-45.
  • [21] Nucleotide sequence of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, a glycoprotein of endoplasmic reticulum. Nature. 1984 Apr 12-18;308(5960):613-7.
  • [22] Domain map of the LDL receptor: sequence homology with the epidermal growth factor precursor. Cell. 1984 Jun;37(2):577-85.
  • [23] HMG CoA reductase: a negatively regulated gene with unusual promoter and 5' untranslated regions. Cell. 1984 Aug;38(1):275-85.
  • [24] The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA. Cell. 1984 Nov;39(1):27-38
  • [25] Mutation in LDL receptor: Alu-Alu recombination deletes exons encoding transmembrane and cytoplasmic domains. Science. 1985 Jan 11;227(4683):140-6.
  • [26] The LDL receptor gene: a mosaic of exons shared with different proteins. Science. 1985 May 17;228(4701):815-22.
  • [27] Cassette of eight exons shared by genes for LDL receptor and EGF precursor. Science. 1985 May 17;228(4701):893-895
  • [28] Membrane-bound domain of HMG CoA reductase is required for sterol-enhanced degradation of the enzyme. Cell. 1985 May;41(1):249-58.
  • [29] Internalization-defective LDL receptors produced by genes with nonsense and frameshift mutations that truncate the cytoplasmic domain. Cell. 1985 Jul;41(3):735-43.
  • [30] 5' end of HMG CoA reductase gene contains sequences responsible for cholesterol-mediated inhibition of transcription. Cell. 1985 Aug;42(1):203-12.
  • [31] Scavenger cell receptor shared. Nature. 1985 Aug 22-28;316(6030):680-1.
  • [32] A receptor-mediated pathway for cholesterol homeostasis. Science. 1986 Apr 4;232(4746):34-47.
  • [33] The J.D. mutation in familial hypercholesterolemia: amino acid substitution in cytoplasmic domain impedes internalization of LDL receptors Cell. 1986 Apr 11;45(1):15-24.
  • [34] Deletion in cysteine-rich region of LDL receptor impedes transport to cell surface in WHHL rabbit. Science. 1986 Jun 6;232(4755):1230-7.
  • [35] Duplication of seven exons in LDL receptor gene caused by Alu-Alu recombination in a subject with familial hypercholesterolemia. Cell. 1987 Mar 13;48(5):827-35.
  • [36] 42 bp element from LDL receptor gene confers end-product repression by sterols when inserted into viral TK promoter. Cell. 1987 Mar 27;48(6):1061-9.
  • [37] Acid-dependent ligand dissociation and recycling of LDL receptor mediated by growth factor homology region. Nature. 1987 Apr 23-29;326(6115):760-765
  • [38] Overexpression of low density lipoprotein (LDL) receptor eliminates LDL from plasma in transgenic mice. Science. 1988 Mar 11;239(4845):1277-81.
  • [39] Inhibition of purified p21ras farnesyl:protein transferase by Cys-AAX tetrapeptides. Cell. 1990 Jul 13;62(1):81-8.
  • [40] Diet-induced hypercholesterolemia in mice: prevention by overexpression of LDL receptors. Science. 1990 Nov 30;250(4985):1273-5
  • [41] Protein farnesyltransferase and geranylgeranyltransferase share a common alpha subunit. Cell. 1991 May 3;65(3):429-34.
  • [42] cDNA cloning and expression of the peptide-binding beta subunit of rat p21ras farnesyltransferase, the counterpart of yeast DPR1/RAM1. Cell. 1991 Jul 26;66(2):327-34.
  • [43] Purification of component A of Rab geranylgeranyl transferase: possible identity with the choroideremia gene product. Cell. 1992 Sep 18;70(6):1049-57.
  • [44] Koch's postulates for cholesterol. Cell. 1992 Oct 16;71(2):187-8.
  • [45] cDNA cloning of component A of Rab geranylgeranyl transferase and demonstration of its role as a Rab escort protein. Cell. 1993 Jun 18;73(6):1091-9
  • [46] SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene. Cell. 1993 Oct 8;75(1):187-97.
  • [47] Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle. Cell. 1994 Mar 11;76(5):865-73.
  • [48] SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell. 1994 Apr 8;77(1):53-62
  • [49] Sterol-regulated release of SREBP-2 from cell membranes requires two sequential cleavages, one within a transmembrane segment. Cell. 1996 Jun 28;85(7):1037-46
  • [50] Sterol resistance in CHO cells traced to point mutation in SREBP cleavage-activating protein. Cell. 1996 Nov 1;87(3):415-26.
  • [51] The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell. 1997 May 2;89(3):331-40.
  • [52] Transport-dependent proteolysis of SREBP: relocation of site-1 protease from Golgi to ER obviates the need for SREBP transport to Golgi. Cell. 1999 Dec 23;99(7):703-12.
  • [53] Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell. 2000 Feb 18;100(4):391-8.
  • [54] Regulated step in cholesterol feedback localized to budding of SCAP from ER membranes. Cell. 2000 Aug 4;102(3):315-23.
  • [55] Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell. 2002 Aug 23;110(4):489-500.

[edit] See also

[edit] References

  1. ^ Soylent Communications, Michael S. Brown, <http://www.nndb.com/people/174/000123802/>. Retrieved on 7 April 2007 
v • d • e
Nobel Laureates in Physiology or Medicine

Baruch Blumberg / Daniel Gajdusek (1976) · Roger Guillemin / Andrew V. Schally / Rosalyn Yalow (1977) · Werner Arber / Daniel Nathans / Hamilton O. Smith (1978) · Allan Cormack / Godfrey Hounsfield (1979) · Baruj Benacerraf / Jean Dausset / George Snell (1980) · Roger Sperry / David H. Hubel / Torsten Wiesel (1981) · Sune Bergström / Bengt I. Samuelsson / John Vane (1982) · Barbara McClintock (1983) · Niels Jerne / Georges Köhler / César Milstein (1984) · Michael Brown / Joseph L. Goldstein (1985) · Stanley Cohen / Rita Levi-Montalcini (1986) · Susumu Tonegawa (1987) · James W. Black / Gertrude B. Elion / George H. Hitchings (1988) · J. Michael Bishop / Harold E. Varmus (1989) · Joseph Murray / E. Donnall Thomas (1990) · Erwin Neher / Bert Sakmann (1991) · Edmond Fischer / Edwin G. Krebs (1992) · Richard J. Roberts / Phillip Sharp (1993) · Alfred G. Gilman / Martin Rodbell (1994) · Edward B. Lewis / Christiane Nüsslein-Volhard / Eric F. Wieschaus (1995) · Peter C. Doherty / Rolf M. Zinkernagel (1996) · Stanley B. Prusiner (1997) · Robert F. Furchgott / Louis Ignarro / Ferid Murad (1998) · Günter Blobel (1999) · Arvid Carlsson / Paul Greengard / Eric Kandel (2000)
Complete roster · 1901–1925 · 1926–1950 · 1951–1975 · 1976–2000 · 2001–present


Persondata
NAME Brown, Michael Stuart
ALTERNATIVE NAMES
SHORT DESCRIPTION American biologist
DATE OF BIRTH April 13, 1941
PLACE OF BIRTH Brooklyn, New York
DATE OF DEATH
PLACE OF DEATH