Michael Stuart Brown Explained
Michael Brown |
Honorific Suffix: | ForMemRS |
Birth Name: | Michael Stuart Brown |
Birth Date: | 1941 4, mf=yes |
Birth Place: | Brooklyn, New York, U.S. |
Nationality: | American |
Field: | Biology |
Known For: | Regulation of cholesterol metabolism |
Children: | two |
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.[1] [2] [3] [4]
Education and early life
Brown was born in Brooklyn, New York, the son of Evelyn, a homemaker, and Harvey Brown, a textile salesman.[3] [5] His family is Jewish.[6] He graduated from Cheltenham High School (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.
Career and research
Moving to the University of Texas Michael liked vann Warner 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. Their discoveries are improving more lives every year, both in the US 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 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.
Brown is also on the Prix Galien USA Committee that "recognizes the technical, scientific and clinical research skills necessary to develop innovative medicines".
Awards and honors
Brown has won numerous awards and honors, including:
Bibliography
- Brown MS, Goldstein JL . Expression of the familial hypercholesterolemia gene in heterozygotes: mechanism for a dominant disorder in man . Science . 185 . 4145 . 61–3 . Jul 1974 . 4366052 . 10.1126/science.185.4145.61 . 1974Sci...185...61B . 31493564.
- Brown MS, Goldstein JL . Regulation of the activity of the low density lipoprotein receptor in human fibroblasts . Cell . 6 . 3 . 307–16 . Nov 1975 . 212203 . 10.1016/0092-8674(75)90182-8 . 28312936.
- Goldstein JL, Basu SK, Brunschede GY, Brown MS . Release of low density lipoprotein from its cell surface receptor by sulfated glycosaminoglycans . Cell . 7 . 1 . 85–95 . Jan 1976 . 181140 . 10.1016/0092-8674(76)90258-0 . 23110979.
- Brown MS, Goldstein JL . Receptor-mediated control of cholesterol metabolism . Science . 191 . 4223 . 150–4 . Jan 1976 . 174194 . 10.1126/science.174194 . 1976Sci...191..150B.
- Goldstein JL, Sobhani MK, Faust JR, Brown MS . Heterozygous familial hypercholesterolemia: failure of normal allele to compensate for mutant allele at a regulated genetic locus . Cell . 9 . 2 . 195–203 . Oct 1976 . 184960 . 10.1016/0092-8674(76)90110-0 . 26944871.
- Brown MS, Goldstein JL . 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 . Dec 1976 . 189940 . 10.1016/0092-8674(76)90130-6 . 6706608.
- Anderson RG, Brown MS, Goldstein JL . Role of the coated endocytic vesicle in the uptake of receptor-bound low density lipoprotein in human fibroblasts . Cell . 10 . 3 . 351–64 . Mar 1977 . 191195 . 10.1016/0092-8674(77)90022-8 . 25657719.
- Goldstein JL, Brown MS, Stone NJ . Genetics of the LDL receptor: evidence that the mutations affecting binding and internalization are allelic . Cell . 12 . 3 . 629–41 . Nov 1977 . 200368 . 10.1016/0092-8674(77)90263-X . 13211975.
- Anderson RG, Goldstein JL, Brown MS . 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 . 1977 . 201867 . 10.1038/270695a0 . 1977Natur.270..695A . 4152556.
- Anderson RG, Vasile E, Mello RJ, Brown MS, Goldstein JL . Immunocytochemical visualization of coated pits and vesicles in human fibroblasts: relation to low density lipoprotein receptor distribution . Cell . 15 . 3 . 919–33 . Nov 1978 . 215316 . 10.1016/0092-8674(78)90276-3 . 35345591.
- Goldstein JL, Anderson RG, Brown MS . Coated pits, coated vesicles, and receptor-mediated endocytosis . Nature . 279 . 5715 . 679–85 . Jun 1979 . 221835 . 10.1038/279679a0 . 1979Natur.279..679G . 4353842.
- Mello RJ, Brown MS, Goldstein JL, Anderson RG . LDL receptors in coated vesicles isolated from bovine adrenal cortex: binding sites unmasked by detergent treatment . Cell . 20 . 3 . 829–37 . Jul 1980 . 6251975 . 10.1016/0092-8674(80)90329-3 . 23996668.
- Brown MS, Kovanen PT, Goldstein JL . Regulation of plasma cholesterol by lipoprotein receptors . Science . 212 . 4495 . 628–35 . May 1981 . 6261329 . 10.1126/science.6261329 . 1981Sci...212..628B.
- Basu SK, Goldstein JL, Anderson RG, Brown MS . Monensin interrupts the recycling of low density lipoprotein receptors in human fibroblasts . Cell . 24 . 2 . 493–502 . May 1981 . 6263497 . 10.1016/0092-8674(81)90340-8 . 29553611.
- Tolleshaug H, Goldstein JL, Schneider WJ, Brown MS . Posttranslational processing of the LDL receptor and its genetic disruption in familial hypercholesterolemia . Cell . 30 . 3 . 715–24 . Oct 1982 . 6291781 . 10.1016/0092-8674(82)90276-8 . 30013697.
- Basu SK, Goldstein JL, Brown MS . Independent pathways for secretion of cholesterol and apolipoprotein E by macrophages . Science . 219 . 4586 . 871–3 . Feb 1983 . 6823554 . 10.1126/science.6823554 . 1983Sci...219..871B.
- Brown MS, Anderson RG, Goldstein JL . Recycling receptors: the round-trip itinerary of migrant membrane proteins . Cell . 32 . 3 . 663–7 . Mar 1983 . 6299572 . 10.1016/0092-8674(83)90052-1 . 34919831.
- Tolleshaug H, Hobgood KK, Brown MS, Goldstein JL . The LDL receptor locus in familial hypercholesterolemia: multiple mutations disrupt transport and processing of a membrane receptor . Cell . 32 . 3 . 941–51 . Mar 1983 . 6299582 . 10.1016/0092-8674(83)90079-X . 39955408.
- Larkin JM, Brown MS, Goldstein JL, Anderson RG . Depletion of intracellular potassium arrests coated pit formation and receptor-mediated endocytosis in fibroblasts . Cell . 33 . 1 . 273–85 . May 1983 . 6147196 . 10.1016/0092-8674(83)90356-2 . 22848187.
- Orci L, Brown MS, Goldstein JL, Garcia-Segura LM, Anderson RG . 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 . Apr 1984 . 6705048 . 10.1016/0092-8674(84)90033-3 . 24586649.
- Chin DJ . Nucleotide sequence of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, a glycoprotein of endoplasmic reticulum . Nature . 308 . 5960 . 613–7 . 1984 . 6546784 . 10.1038/308613a0 . vanc . Gil G . Russell DW . 3 . Liscum . Laura . Luskey . Kenneth L. . Basu . Sandip K. . Okayama . Hiroto . Berg . Paul . Goldstein . Joseph L. . 1984Natur.308..613C . 4308995.
- Russell DW, Schneider WJ, Yamamoto T, Luskey KL, Brown MS, Goldstein JL . Domain map of the LDL receptor: sequence homology with the epidermal growth factor precursor . Cell . 37 . 2 . 577–85 . Jun 1984 . 6327078 . 10.1016/0092-8674(84)90388-X . 29839468.
- Reynolds GA . HMG CoA reductase: a negatively regulated gene with unusual promoter and 5' untranslated regions . Cell . 38 . 1 . 275–85 . Aug 1984 . 6088070 . 10.1016/0092-8674(84)90549-X . vanc . Basu SK . Osborne TF . 3 . Chin . Daniel J. . Gil . Gregorio . Brown . Michael S. . Goldstein . Joseph L. . Luskey . Kenneth L. . 11644830.
- Yamamoto T . The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA . Cell . 39 . 1 . 27–38 . Nov 1984 . 6091915 . 10.1016/0092-8674(84)90188-0 . vanc . Davis CG . Brown MS . 3 . Schneider . Wolfgang J. . Casey . M.Linette . Goldstein . Joseph L. . Russell . David W. . 25822170.
- Lehrman MA, Schneider WJ, Südhof TC, Brown MS, Goldstein JL, Russell DW . Mutation in LDL receptor: Alu-Alu recombination deletes exons encoding transmembrane and cytoplasmic domains . Science . 227 . 4683 . 140–6 . Jan 1985 . 3155573 . 10.1126/science.3155573 . 4449727 . 1985Sci...227..140L.
- Südhof TC, Goldstein JL, Brown MS, Russell DW . The LDL receptor gene: a mosaic of exons shared with different proteins . Science . 228 . 4701 . 815–22 . May 1985 . 2988123 . 10.1126/science.2988123 . 4450672 . 1985Sci...228..815S.
- Südhof TC, Russell DW, Goldstein JL, Brown MS, Sanchez-Pescador R, Bell GI . Cassette of eight exons shared by genes for LDL receptor and EGF precursor . Science . 228 . 4701 . 893–5 . May 1985 . 3873704 . 10.1126/science.3873704 . 1985Sci...228..893S.
- Gil G, Faust JR, Chin DJ, Goldstein JL, Brown MS . Membrane-bound domain of HMG CoA reductase is required for sterol-enhanced degradation of the enzyme . Cell . 41 . 1 . 249–58 . May 1985 . 3995584 . 10.1016/0092-8674(85)90078-9 . 22530611.
- Lehrman MA, Goldstein JL, Brown MS, Russell DW, Schneider WJ . Internalization-defective LDL receptors produced by genes with nonsense and frameshift mutations that truncate the cytoplasmic domain . Cell . 41 . 3 . 735–43 . Jul 1985 . 3924410 . 10.1016/S0092-8674(85)80054-4 . 27773467.
- Osborne TF, Goldstein JL, Brown MS . 5' end of HMG CoA reductase gene contains sequences responsible for cholesterol-mediated inhibition of transcription . Cell . 42 . 1 . 203–12 . Aug 1985 . 3860301 . 10.1016/S0092-8674(85)80116-1 . 37319421.
- Brown MS, Goldstein JL . Scavenger cell receptor shared . Nature . 316 . 6030 . 680–1 . 1985 . 4033768 . 10.1038/316680a0 . 4349775.
- Brown MS, Goldstein JL . A receptor-mediated pathway for cholesterol homeostasis . Science . 232 . 4746 . 34–47 . Apr 1986 . 3513311 . 10.1126/science.3513311 . 1986Sci...232...34B.
- Davis CG, Lehrman MA, Russell DW, Anderson RG, Brown MS, Goldstein JL . The J.D. mutation in familial hypercholesterolemia: amino acid substitution in cytoplasmic domain impedes internalization of LDL receptors . Cell . 45 . 1 . 15–24 . Apr 1986 . 3955657 . 10.1016/0092-8674(86)90533-7 . 8147673.
- Yamamoto T, Bishop RW, Brown MS, Goldstein JL, Russell DW . Deletion in cysteine-rich region of LDL receptor impedes transport to cell surface in WHHL rabbit . Science . 232 . 4755 . 1230–7 . Jun 1986 . 3010466 . 10.1126/science.3010466 . 4451858 . 1986Sci...232.1230Y.
- Lehrman MA, Goldstein JL, Russell DW, Brown MS . Duplication of seven exons in LDL receptor gene caused by Alu-Alu recombination in a subject with familial hypercholesterolemia . Cell . 48 . 5 . 827–35 . Mar 1987 . 3815525 . 10.1016/0092-8674(87)90079-1 . 35887205.
- Südhof TC, Russell DW, Brown MS, Goldstein JL . 42 bp element from LDL receptor gene confers end-product repression by sterols when inserted into viral TK promoter . Cell . 48 . 6 . 1061–9 . Mar 1987 . 3030558 . 10.1016/0092-8674(87)90713-6 . 42788737.
- Davis CG, Goldstein JL, Südhof TC, Anderson RG, Russell DW, Brown MS . Acid-dependent ligand dissociation and recycling of LDL receptor mediated by growth factor homology region . Nature . 326 . 6115 . 760–5 . 1987 . 3494949 . 10.1038/326760a0 . 1987Natur.326..760D . 4347695.
- Hofmann SL, Russell DW, Brown MS, Goldstein JL, Hammer RE . Overexpression of low density lipoprotein (LDL) receptor eliminates LDL from plasma in transgenic mice . Science . 239 . 4845 . 1277–81 . Mar 1988 . 3344433 . 10.1126/science.3344433 . 1988Sci...239.1277H.
- Reiss Y, Goldstein JL, Seabra MC, Casey PJ, Brown MS . Inhibition of purified p21ras farnesyl:protein transferase by Cys-AAX tetrapeptides . Cell . 62 . 1 . 81–8 . Jul 1990 . 2194674 . 10.1016/0092-8674(90)90242-7 . 30887422.
- Yokode M, Hammer RE, Ishibashi S, Brown MS, Goldstein JL . Diet-induced hypercholesterolemia in mice: prevention by overexpression of LDL receptors . Science . 250 . 4985 . 1273–5 . Nov 1990 . 2244210 . 10.1126/science.2244210 . 1990Sci...250.1273Y.
- Seabra MC, Reiss Y, Casey PJ, Brown MS, Goldstein JL . Protein farnesyltransferase and geranylgeranyltransferase share a common alpha subunit . Cell . 65 . 3 . 429–34 . May 1991 . 2018975 . 10.1016/0092-8674(91)90460-G . 54388220.
- Chen WJ, Andres DA, Goldstein JL, Russell DW, Brown MS . 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 . Jul 1991 . 1855253 . 10.1016/0092-8674(91)90622-6 . 36722957.
- Seabra MC, Brown MS, Slaughter CA, Südhof TC, Goldstein JL . Purification of component A of Rab geranylgeranyl transferase: possible identity with the choroideremia gene product . Cell . 70 . 6 . 1049–57 . Sep 1992 . 1525821 . 10.1016/0092-8674(92)90253-9 . 26223659.
- Brown MS, Goldstein JL . Koch's postulates for cholesterol . Cell . 71 . 2 . 187–8 . Oct 1992 . 1423585 . 10.1016/0092-8674(92)90346-E . 33048207.
- Andres DA . cDNA cloning of component A of Rab geranylgeranyl transferase and demonstration of its role as a Rab escort protein . Cell . 73 . 6 . 1091–9 . Jun 1993 . 8513495 . 10.1016/0092-8674(93)90639-8 . vanc . Seabra MC . Brown MS . 3 . Armstrong . Scott A. . Smeland . Tor E. . Cremers . Frans P.M. . Goldstein . Joseph L. . 26120573.
- Yokoyama C . 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 . Oct 1993 . 8402897 . 10.1016/S0092-8674(05)80095-9 . vanc . Wang X . Briggs MR . 3 . Admon . A . Wu . J . Hua . X . Goldstein . JL . Brown . MS . 2784016.
- Garcia CK, Goldstein JL, Pathak RK, Anderson RG, Brown MS . Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle . Cell . 76 . 5 . 865–73 . Mar 1994 . 8124722 . 10.1016/0092-8674(94)90361-1 . 22137883.
- Wang X, Sato R, Brown MS, Hua X, Goldstein JL . SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis . Cell . 77 . 1 . 53–62 . Apr 1994 . 8156598 . 10.1016/0092-8674(94)90234-8 . 44899129.
- Sakai J, Duncan EA, Rawson RB, Hua X, Brown MS, Goldstein JL . Sterol-regulated release of SREBP-2 from cell membranes requires two sequential cleavages, one within a transmembrane segment . Cell . 85 . 7 . 1037–46 . Jun 1996 . 8674110 . 10.1016/S0092-8674(00)81304-5 . 6130686 . free.
- Hua X, Nohturfft A, Goldstein JL, Brown MS . Sterol resistance in CHO cells traced to point mutation in SREBP cleavage-activating protein . Cell . 87 . 3 . 415–26 . Nov 1996 . 8898195 . 10.1016/S0092-8674(00)81362-8 . 1963192 . free.
- Brown MS, Goldstein JL . The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor . Cell . 89 . 3 . 331–40 . May 1997 . 9150132 . 10.1016/S0092-8674(00)80213-5 . 17882616 . free.
- DeBose-Boyd RA, Brown MS, Li WP, Nohturfft A, Goldstein JL, Espenshade PJ . Transport-dependent proteolysis of SREBP: relocation of site-1 protease from Golgi to ER obviates the need for SREBP transport to Golgi . Cell . 99 . 7 . 703–12 . Dec 1999 . 10619424 . 10.1016/S0092-8674(00)81668-2 . free.
- Brown MS, Ye J, Rawson RB, Goldstein JL . Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans . Cell . 100 . 4 . 391–8 . Feb 2000 . 10693756 . 10.1016/S0092-8674(00)80675-3 . 12194770 . free.
- Nohturfft A, Yabe D, Goldstein JL, Brown MS, Espenshade PJ . Regulated step in cholesterol feedback localized to budding of SCAP from ER membranes . Cell . 102 . 3 . 315–23 . Aug 2000 . 10975522 . 10.1016/S0092-8674(00)00037-4 . 18054832 . free.
- Yang T . Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER . Cell . 110 . 4 . 489–500 . Aug 2002 . 12202038 . 10.1016/S0092-8674(02)00872-3 . vanc . Espenshade PJ . Wright ME . 3 . Yabe . Daisuke . Gong . Yi . Aebersold . Ruedi . Goldstein . Joseph L. . Brown . Michael S. . 15052132 . free.
See also
Notes and References
- Web site: Biography: Michael S. Brown . The Notable Names Database . Soylent Communications. 2008 . 2008-06-15.
- Web site: Michael Brown - Nobel Prize Inspiration Initiative . Nobelprizeii.org . 2015-11-06.
- Web site: Michael S. Brown - Biographical . Nobelprize.org . 1941-04-13 . 2015-11-06.
- Web site: Michael S. Brown - Nobel Lecture: A Receptor-Mediated Pathway for Cholesterol Homeostasis . Nobelprize.org . 1985-12-08 . 2015-11-06.
- Web site: BROWN (Brown), Michael, photo, biography . Persona.rin.ru . 1941-04-13 . 2015-11-06.
- Web site: Jewish Nobel Prize Winners in Medicine . 2023-03-30 . www.jinfo.org.
- Web site: Earl and Thressa Stadtman Distinguished Scientist Award . Asbmb.org . 2015-11-06.
- Web site: University of Texas Southwestern Medical Center Leaders to Receive Research!America Advocacy Award . Research!America . 2007-03-21 . 2015-11-06.
- http://www.wilsoncenter.org/sites/default/files/psawardeesfeb2012.pdf
- Web site: Herbert Tabor Research Award . Asbmb.org . 2015-11-06.
- Web site: Albany Medical College: 2003 . Amc.edu . 2015-08-14 . 2015-11-06.
- Web site: Presentation of the Kober Medal to Joseph L. Goldstein and Michael S. Brown . PDF . Daniel W. Foster . Jean D. Wilson . Jci.org . 2015-11-06.
- http://www.warrenalpert.org/award/#Winners
- Web site: https://web.archive.org/web/20151106214111/https://royalsociety.org/people/michael-brown-11147/. 2015-11-06. Professor Michael Brown ForMemRS. Royal Society. London.
- Web site: APS Member History .
- Web site: Golden Plate Awardees of the American Academy of Achievement . www.achievement.org. American Academy of Achievement.
- Web site: The Nobel Prize in Physiology or Medicine 1985 . nobelprize.org . The Nobel Foundation . 18 October 2022.
- Web site: 1985 Basic Medical Research Award . The Lasker Foundation . 2007-09-16 . 2015-11-06 . dead . https://web.archive.org/web/20150913005532/http://www.laskerfoundation.org/awards/1985basic.htm . 2015-09-13 .
- Web site: Past ASHG Award Recipients . ASHG . 2015-11-06 . https://web.archive.org/web/20141003163707/http://www.ashg.org/pages/awards_pastrecipients.shtml#allan . 2014-10-03 . dead .
- Web site: Horwitz Prize Awardees . cuimc.columbia.edu . 20 June 2018 . Columbia University . 18 October 2022.
- Web site: Joseph L. Goldstein . Gairdner . 2015-11-06.
- Web site: Michael Stuart Brown .
- Web site: Michael Brown. www.nasonline.org. 23 March 2018.
- Web site: Richard Lounsbery Award . Nasonline.org . 2015-11-06.
- http://passanofoundation.org/#/past-recipients/4513087930
- Web site: Pfizer Award in Enzyme Chemistry . Divbiolchem.org . 2015-11-06.
- Web site: Heinrich Wieland Prize Laureates 1970 - 1979 . Boehringer Ingelheim Stiftung . Boehringer Ingelheim Stiftung . 18 October 2022.