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  • B.S., University of Minnesota, Minneapolis, 1955

  • M.D., University of Minnesota, Minneapolis, 1957

  • Ph.D., University of Minnesota, Minneapolis, 1961

  • Visiting Scientist, MRC Unit, London, 1961-1962

  • Research Fellow, Harvard University, 1962-1963

  • Assistant Professor, University of Minnesota Medical School, 1963-1964

  • Faculty member, University of Illiniois, 1964-1972

  • Faculty member, Rice University, 1972-present

  • Department of Biochemistry and Cell Biology

  • Department of Chemistry

  • Biochemistry and chemistry.


    Email: schroepf@bioc.rice.edu
    Phone: (713)348-0000


                      


    Regulators of Cholesterol Metabolism

                      


    Campus Directory

  • George J. Schroepfer
    Ralph and Dorothy Looney Professor (Deceased)

    Our research has concerned various aspects of the chemistry and biochemistry of cholesterol (and other compounds derived from mevalonic acid), sphingolipids, fatty acids, and other natural products. We have had considerable interest in the mechanisms and stereospecificity of enzymatic reactions.

    A major general area of current interest concerns the regulation of the formation and metabolism of cholesterol. A portion of this work involves studies of a number of oxygenated sterols, prepared by chemical synthesis, which have been found to be very potent inhibitors of cholesterol biosynthesis. We have significant experience in the isolation, characterization, quantitation, and metabolism of naturally occurring oxygenated sterols. We seek the development of improved methods for the analysis of oxygenated sterols so as to permit application to a wide variety of biological and medical studies. Our research on oxysterols is very broad in scope and in experimental approaches.

    The main focus of our research will be on oxygenated sterols and sphingolipids. Some of these compounds represent potential normal regulators of cell function and replication. We are currently exploring interrelationships in the biosynthesis, metabolism, and effects of sphingolipids and sterols.


    Selected Publications

    Su, X., Siddiqui, A.U., Swaminathan, S., Wilson, W.K., and Schroepfer, G.J., Jr., "Preparation of 25,26,26,26,27,27,27-Heptafluoro-15-ketosterols Labeled at C-23 with Deuterium or Tritium," J. Labelled Compounds Radiopharm., 41 (1998): 63-74.

    Schroepfer, G.J., Jr., Ruan, B., Wilson, W.K., Watanabe, S., and Eppig, J.J., "Synthetic Versions of the Sterols FF-MAS and T-MAS Affect Meiosis in Mouse Oocytes," Program Addendum and Late-Breaking Abstracts, American Society for Biochemistry and Molecular Biology , (1998): A1. (Washington, D.C.)

    Ruan, B., Wilson, W.K., and Schroepfer, G.J., Jr., "Silver Ion Chromatography and 1H NMR for Sterol Analysis: Application to Plasma Sterols in Developmental Disorder," FASEB J., 12 (1998): A1387.

    Su, S., Siddiqui, A.U., Swaminathan, S., Wilson, W.K., and Schroepfer, G.J., Jr., "Preparation of 25,26,26,26,27,27,27-Heptafluoro-15-ketosterols Labeled at C-23 with Deuterium or Tritium, Erratum," J. Labelled Compounds Radiopharm., 41 (1998): 253-254.

    Ruan, B., Wilson, W.K., and Schroepfer, G.J., Jr., "An Alternative Synthesis of 4,4-Dimethyl-5a-cholesta-8,14,24-trien-3ß-ol, an Intermediate in Sterol Biosynthesis and a Reported Activator of Meiosis and of Nuclear Orphan Receptor LXRa," Bioorg. Med. Chem. Lett., 8 (1998): 233-236.

    Ruan, B., Lew, E., and Schroepfer, G.J., Jr., "Preparation of Isoprenoid Alcohols and Acids, Regulators of Cellular Processes with Applications of Ag+-HPLC," Abstracts, 89th AOCS Annual Meeting and Expo, (1998): 91. Chicago, IL, May 10-13

    Smith, T.B., Sharma, C., Li, S., Schroepfer, G.J., Jr., and Needleman, D.H., "Modulation of Ca2+-release Channel Activity by Phytosphingosine," Biophys. J., 74 (1998): A60.

    Ruan, B., Watanabe, S., Eppig, J.J., Kwoh, C., Dzidic, N., Pang, J., Wilson, W.K., and Schroepfer, G.J., Jr., "Sterols Affecting Meiosis: Novel Chemical Syntheses and the Biological Activity and Spectral Properties of the Synthetic Sterols," J. Lipid Res., 39 (1998): 2005-2020.

    Carroll, J.N., Pinkerton, F.D., Su, X., Gerst, N., Wilson, W.K., and Schroepfer, G.J., Jr., "Sterol Synthesis. Synthesis of 3b-Hydroxy-25,26,26,26,27,27,27-heptafluorocholest-5-en-7-one and its Effects on HMG-CoA reductase Activity in Chinese Hamster Ovary Cells, on ACAT Activity in Rat Jejunal Microsomes, and Serum Cholesterol Levels in Rats," Chem. Phys. Lipids, 94 (1998): 209-225.

    Swaminathan, S., Siddiqui, A.U., Gerst, N., Pinkerton, F.D., Kisic, A., Kim, L.J., Wilson, W.K., and Schroepfer, G.J., Jr., "Inhibitors of Sterol Synthesis. Metabolism-based Design and Construction of a New Analog of 3ß-Hydroxy-5a-cholest-8(14)-en-3ß-ol-15-one and its Effects in Cultured Mammalian Cells and in Rats," J. Lipid Res., 36 (1995): 767-786.

    Kisic, A., Tsuda, M., Kulmacz, R.J., Wilson, W.K., and Schroepfer, G.J., Jr., "Sphingolipid Bases. A Revisitation of the O-Methyl Derivatives of Sphingosine. Isolation and Characterization of Diacetate Derivatives, with Revised 13C Nuclear Magnetic Resonance Assignments for D-Erythro-sphingosine," J. Lipid Res, 36 (1995): 787-803.

    Schroepfer, G.J., Jr., "Design of New Oxysterols for Regulation of Cholesterol Metabolism," Current Pharmaceutical Design, 2 (1996): 103-120.

    Wilson, W.K., Sumpter, R.M., Warren, J.J., Rogers, P.S., Ruan, B., and Schroepfer, G.J., Jr., "Analysis of Unsaturated C27 Sterols by Nuclear Magnetic Resonance Spectroscopy," J. Lipid Res., 37 (1996): 1529-1555.

    Ruan, B., Pang, J., Wilson, W.K., and Schroepfer, G.J., Jr., "Concerning the Thermolability of Cholesta-5,8-dien-3ß-ol, a Sterol that Accumulates in Blood and Tissues in a Human Genetic Developmental Disorder," Bioorg. Med. Chem. Lett., 6 (1996): 2421-2424.

    Ruan, B., Shey, J., Gerst, N., Wilson, W.K., and Schroepfer, G.J., Jr., "Silver Ion High Pressure Liquid Chromatography Provides Unprecedented Separation of Sterols: Application to the Enzymatic Formation of Cholesta-5,8-dien-3ß-ol," Proc. Natl. Acad. Sci., 93 (1996): 11603-11608.

    Needleman, D.H., Aghdasi, B., Seryshev, A.B., Schroepfer, G.J., Jr., and Hamilton, S.L., "Modulation of Skeletal Muscle Ca+2-Release Channel Activity by Sphingosine," Am. J. Physiol., 272 (1997): C1465-C1474.

    Siddiqui, A.U., Swaminathan, S., Su, X., Wilson, W.K., and Schroepfer, G.J., Jr., "Inhibitors of Sterol Synthesis. Synthesis and Spectral Properties of 3ß-Hydroxy-25,26,26,26,27,27,27-heptafluoro-5a-cholestan-15-one," Chem. Phys. Lipids, 86 (1997): 95-119.

    Gerst, N., Ruan, B., Pang, J., Wilson, W.K., and Schroepfer, G.J., Jr., "An Updated Look at the Analysis of Unsaturated C27 Sterols by Gas Chromatography and Mass Spectrometry," J. Lipid Res., 38 (1997): 1685-1701.

    Ruan, B., Gerst, N., Emmons, G.T., Shey, J., and Schroepfer, G.J., Jr., "Sterol Synthesis. A Timely Look at the Capabilities of Conventional and Silver Ion High Performance Liquid Chromatography for the Separation of C27 Sterols Related to Cholesterol Biosynthesis," J. Lipid Res., 38 (1997): 2615-2626.

    Forman, B.M, Ruan, B., Chen, J., Schroepfer, G.J., Jr., and Evans, R.M., "The Orphan Nuclear Receptor LXRa is Positively and Negatively Regulated by Distinct Products of Mevalonate Metabolism," Proc. Natl. Acad. Sci. USA, 94 (1997): 10588-10593.


    Presentations

    "Applications of Simple Chemistry to Biomedical Problems Involving Cholesterol and Other Lipids," School of Chemical Science, University of Illinois, Urbana, Illinois (February 14, 1997).


    Research Topics

    Sphingolipids and Sterols: Metabolism and Interactions. National Institutes of Health.

    Role of Defects in Sterol Biosynthesis in the Pathogenesis of Congenital Developmental Diseases. March of Dimes Birth Defects Foundation.

    Synthesis, Structure, and Spectral Properties of Natural Products. Robert A Welch Foundation.

    Regulatory Mechanism of Enzymes in the Later Stages of Cholesterol Biosynthesis. Ministry of Education, Science, and Culture of Japan, Scientific Research Program.   [with T. Ono and others]

    Development of Oxygenated and Fluorinated Sterols for Potential Use in Medicine. Texas Advanced Technology Program.

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