Moving to the University of Texas Health Science Center in Dallas, now theUT Southwestern Medical Center, Brown and colleagueJoseph L. Goldstein researched cholesterol metabolism and discovered that human cells havelow-density lipoprotein (LDL) receptors that extract cholesterol from the bloodstream. The lack of sufficient LDL receptors is implicated infamilial 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 ofstatin drugs, thecholesterol-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 (proteinprenylation) incancer. In 1984 he was awarded theLouisa Gross Horwitz Prize fromColumbia University together withJoseph L. Goldstein (co-recipient of 1985 Nobel Prize in Physiology or Medicine). In 1988, Brown received theNational Medal of Science for his contributions to medicine.
In 1993, their traineesXiaodong Wang and Michael Briggs purified thesterol 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]
Brown is also on the Prix Galien USA Committee that "recognizes the technical, scientific and clinical research skills necessary to develop innovative medicines".[citation needed]
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:10.1016/0092-8674(76)90258-0.PMID181140.S2CID23110979.
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:10.1016/0092-8674(76)90110-0.PMID184960.S2CID26944871.
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:10.1016/0092-8674(76)90130-6.PMID189940.S2CID6706608.
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:10.1016/0092-8674(77)90022-8.PMID191195.S2CID25657719.
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:10.1016/0092-8674(77)90263-X.PMID200368.S2CID13211975.
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:1977Natur.270..695A.doi:10.1038/270695a0.PMID201867.S2CID4152556.
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:10.1016/0092-8674(78)90276-3.PMID215316.S2CID35345591.
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:10.1016/0092-8674(81)90340-8.PMID6263497.S2CID29553611.
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:10.1016/0092-8674(82)90276-8.PMID6291781.S2CID30013697.
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:10.1016/0092-8674(83)90079-X.PMID6299582.S2CID39955408.
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:10.1016/0092-8674(83)90356-2.PMID6147196.S2CID22848187.
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:10.1016/0092-8674(84)90033-3.PMID6705048.S2CID24586649.
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:10.1016/0092-8674(84)90388-X.PMID6327078.S2CID29839468.
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:10.1016/0092-8674(84)90549-X.PMID6088070.S2CID11644830.
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:1985Sci...228..893S.doi:10.1126/science.3873704.PMID3873704.
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:10.1016/0092-8674(85)90078-9.PMID3995584.S2CID22530611.
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:10.1016/S0092-8674(85)80054-4.PMID3924410.S2CID27773467.
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:10.1016/S0092-8674(85)80116-1.PMID3860301.S2CID37319421.
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:10.1016/0092-8674(86)90533-7.PMID3955657.S2CID8147673.
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:10.1016/0092-8674(87)90079-1.PMID3815525.S2CID35887205.
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:10.1016/0092-8674(87)90713-6.PMID3030558.S2CID42788737.
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:1987Natur.326..760D.doi:10.1038/326760a0.PMID3494949.S2CID4347695.
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:1988Sci...239.1277H.doi:10.1126/science.3344433.PMID3344433.
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:10.1016/0092-8674(90)90242-7.PMID2194674.S2CID30887422.
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:1990Sci...250.1273Y.doi:10.1126/science.2244210.PMID2244210.
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:10.1016/0092-8674(91)90460-G.PMID2018975.S2CID54388220.
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:10.1016/0092-8674(91)90622-6.PMID1855253.S2CID36722957.
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:10.1016/0092-8674(92)90253-9.PMID1525821.S2CID26223659.
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:10.1016/0092-8674(93)90639-8.PMID8513495.S2CID26120573.
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:10.1016/S0092-8674(05)80095-9.PMID8402897.S2CID2784016.
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:10.1016/0092-8674(94)90361-1.PMID8124722.S2CID22137883.
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:10.1016/0092-8674(94)90234-8.PMID8156598.S2CID44899129.
