Harry V. Gelboin, Ph.D.

hgg@helix.nih.gov

Dr. Gelboin received his Ph.D. at the University of Wisconsin in 1958, spent three years at the National Institutes of Mental Health and then joined the National Cancer Institute. Afterwards, he became Section Head and in 1967 became Chief of the Laboratory of Molecular Carcinogenesis. He received an honorary D.Sc from Inonu University, Turkey and numerous Awards and Honorary Lectureships. Among these are the Claude Bernard Award (Montreal), Radiological Society of North America New Horizons Award, Franz Bielschowsky Honorary Lecture (New Zealand), Nakasone Award Lecture (Tokyo), Princess Takamatsu Symposium, Keynote Speaker (Tokyo), Glinos Foundation Lecture (Athens), Smith-Kline French Lectures (2), Israel Cancer Society Lecture (Tel-Aviv), Keynote Lecture, Molecular Carcinogenesis Conference (Alghero). He is the author or co-author of more than 400 articles and co-editor of nine books. He is among the 300 most cited scientists worldwide from 1965-1978 and among the 500 most cited scientists 1973-1982. He has lectured extensively in the United States and 26 foreign countries.

RESEARCH

Development of a system of analysis useful for Drug Discovery and the reduction of Adverse Drug Reactions (ADR): The system utilizes a comprehensive library of monoclonal antibodies specific and inhibitory to each of the human liver cytochrome P450s responsible for the metabolism of drugs and non-drug xenobiotics. The P450s also metabolize certain classes of endobiotics such as steroids, prostaglandins and arachidonic acid. The single or combinatorial use of the monoclonal antibodies (MAbs) "reaction phenotype" that is, determine the quantitative metabolic contribution of each cytochrome P450 isoform to a substrates metabolism. Thus, the MAb system identifies drugs or metabolic pathways catalyzed by a single P450 and those catalyzed by two or more cytochrome P450s. The drugs metabolized by a single P450 can be used as markers for in vivo analysis of a patients cytochrome P450 phenotype. The MAb system also identifies drugs metabolized by a polymorphic P450 and drugs metabolized by a common P450 which may result in drug-drug toxic reactions. The library of monoclonal antibodies are specific and inhibitory to human cytochrome P450 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. The MAb system is a new, specific and precise method for quantitating drug metabolism catalyzed by each cytochrome P450. The MAb system can also analyze New Chemical Entities (NCEs) for Drug Discovery as well as currently used drugs, for the reduction of drug toxicity due to Adverse Drug Reactions (ADR). The MAb system should thereby yield information for the improvement of Drug Therapeutics.
 
 

Current Publications:

  1. Krausz KW, Goldfarb I, Yang TJ, Gonzalez FJ, and Gelboin HV (2000) An Inhibitory Monoclonal Antibody to Human Cytochrome P450 that Specifically Binds and Inhibits P450 2C9II, an Allelic Variant of P450 2C9 Having a Single Amino Acid Change Arg144 Cys. Xenobiotica 30: 619-625.
  2. Sai Y, Yang TJ, Krausz KW, Gonzalez FJ and Gelboin HV (1999) An Inhibitory Monoclonal Antibody to Human Cytochrome P450 2A6 Defines its Role in the Metabolism of Coumarin, 7-ethoxycoumarin and 4-nitroanisole in Human Liver. Pharmacogenetics 9: 229-237.
  3. Chen, S.C., Wang, X., Xu, G., Zhou, L., Vennerstrom, J.L., Gonzalez, F.J., Gelboin, H.V., Mirvish, S.S. (1999) Depentylation of [3H-pentyl]methyl-n-amylnitrosamine by rat esophageal and liver microsomes and by rat and human cytochrome P450 isoforms. Cancer Res 59: 91-98.
  4. Gelboin HV, Krausz KW, Gonzalez FJ, and Yang TJ (1999) Inhibitory Monoclonal Antibodies to Human Cytochrome P450 Enzymes: A New Avenue for Drug Discovery. Trends Pharmacol Sci 20(11): 432-438.
  5. Yang, T.J., Krausz, K.W., Sai, Y., Gonzalez, F.J. and Gelboin, H.V. (1999) Eight Inhibitory Monoclonal Antibodies Define the Role of Individual P450s in Human Liver Microsomal Diazepam, 7-Ethoxycoumarin and Imipramine Metabolism. Drug Metab. Dispos. 27: 102-109.
  6. Yang, T.J., Sai, Y., Krausz, K.W., Gonzalez, F.J. and Gelboin, H.V. (1998) Inhibitory Monoclonal Antibodies to Human cytochrome P450 1A2: analysis of phenacetin o-Deethylation in human liver. Pharmacogenetics 8: 375-382.
  7. Shou, M., Martinet, M., Korzekwa, K.R., Krausz, K.W., Gonzalez, F.J. and Gelboin, H.V. (1998) Role of Human Cytochrome P450 3A4 and 3A5 in the Metabolism of Taxotere and its Derivatives: Enzyme Specificity, Interindividual Distribution and Metabolic Contribution in Human Liver. Pharmacogenetics 8: 391-401.
  8. Yang, T.J., Shou, M., Korzekwa, K.K., Gonzalez, F.J., Gelboin, H.V. and Yang, S.K. (1998) Role of cDNA-Expressed Human Cytochromes P450 in the Metabolism of Diazepam. Biochem. Pharmacol. 55: 889-896.
  9. Yang TJ, Krausz KW, Shou M, Yang SK, Buters JTM, Gonzalez FJ and Gelboin HV (1998) Inhibitory Monoclonal Antibody to Human Cytochrome P450 2B6. Biochem Pharmacol 55: 1633-1640.
  10. Gelboin HV, Shou M, Goldfarb I, Yang TJ and Krausz KW (1998) Monoclonal Antibodies to Cytochrome P450 in Methods in Molecular Biology: Cytochrome P450 Protocols. (IR Phillips and EA Shephard, eds) pp 227-237, Humana Press Inc., Totowa, New Jersey
  11. Gelboin, H.V., Krausz, K.W., Shou, M., Gonzalez, F.J. and Yang, T.J. (1997) A Monoclonal Antibody Inhibitory to Human P450 2D6: A Paradigm for use in Combinatorial Determination of Individual P450 role in Specific Drug Tissue Metabolism. Pharmacogenetics 7: 469-477.

Previous publications

  1. Gelboin HV, Goldfarb I, Krausz KW, Grogan J, Korzekwa KR, Gonzalez FJ and Shou M (1996) Inhibitory and Noninhibitory Monoclonal Antibodies to Human Cytochrome P450 2E1. Chem Res Toxicl 9:1023-1030.
  2. Gelboin HV, Krausz KW, Goldfarb I, Buters JTM, Yang SK, Gonzalez FJ, Korzekwa KR and Shou M (1995) Inhibitory and Non Inhibitory Monoclonal Antibodies to Human Cytochrome P450 3A3/4. Biochem Pharmacol 50:1841-1850.
  3. Gelboin HV (1993) Monoclonal Antibodies and Cytochrome P450. Pharmacol Rev 45: 413-453.
  4. Battula N, Sagara J and Gelboin HV (1987) Expression of P1-450 and P3-450 DNA Coding Sequences as Enzymatically Active Ctochromes P-450 in Mammalian Cells. Proc Natl Acad Sci USA 84: 4073-4077.
  5. Park SS, Fujino T, West D, Guengerich FP and Gelboin HV (1982) Monoclonal Antibodies Inhibiting Enzyme Activity of Cytochrome P450 from 3-methcholanthracene-treated Rats. Cancer Res 42: 1798-1808.
  6. Fujino T, Park SS, West D and Gelboin HV (1982) Phenotyping of Cytochromes P-450 in Human Tissues with Monoclonal Antibodies. Proc Natl Acad Sci USA 79: 3682-3686.
  7. Park SS, Person AV, Coon MJ, and Gelboin HV (1980) Monoclonal Antibodies to Rabbit Liver Cytochrome P450 LM2. FEBS Lett 116: 231-235.
  8. Gelboin HV (1980) Benzo[a]pyrene Metabolism, Activation and Carcinogenesis: Role of Mixed-Function Oxidases and Related Enzymes. Physiol Rev 60: 1107-1166.
  9. Huberman E, Sachs L, Yang SK and Gelboin HV (1976) Identification of the Mutagenic Metabolites of Benzo(a)pyrene in Mammalian Cells. Proc Natl Acad Sci 73: 607-611.
  10. Whitlock Jr. JP, Cooper HL and Gelboin HV (1972) Aryl Hydrocarbon (Benzopyrene) Hydroxylase is Stimulated in Human Lymphocytes by Mitogens and Benz[a]anthracene. Science 177: 618-619.
  11. Gelboin HV, Wiebel FJ and Diamond L (1970) Dimethylbenzathracene Tumorigenesis and Aryl Hydrocarbon Hydroxylase in Mouse Skin: Inhibition by 7,8-Benzoflavone. Science 170(954): 169-171.
  12. Gelboin HV (1969) A Microsome-Dependent Binding of Benzo[a]pyrene to DNA. Cancer Research 29(6): 1272-1276.
  13. Nebert DW, Winker J and Gelboin HV (1969) Aryl Hydrocarbon Hydroxylase Activity in Human Placenta from Cigarette Smoking and Nonsmoking Women. Cancer Research 29(10): 1763-1769.
  14. Nebert DW and Gelboin HV (1969) The In Vivo and In Vitro Induction of Aryl Hydrocarbon Hydroxylase in Mammalian Cell of Different Species, Tissues, Strains and Developmental and Hormonal States. Arch Biochem and Biophys 134(1): 76-89.
  15. Diamond L and Gelboin HV (1969) Alpha-naphthoflavone: An Inhibitor of Hydrocarbon Cytotoxicity and Microsomal Hydroxylase. Science 166(908): 1023-1025.
  16. Gelboin HV, Huberman E and Sachs L (1969) Enzymatic Hydroxylation of Benezopyrene and its Relationship to Cytotoxicity. Proc Natl Acad Sci 64(4): 1188-1194.
  17. Nebert DW and Gelboin HV (1968) Substrate-Inducible Microsomal Aryl Hydroxylase in Mammalian Cell Culture: II. Cellular Responses During Enzyme Induction. J Biol Chem 243(23): 6250-6261.
  18. Gelboin HV (1968) Carcinogenesis and Gene Action, Franz Bielschowsky Memorial Lecture. New Zealand Med J 67(426): 111-126.
  19. Gelboin HV (1967) Carcinogens, Enzyme Induction and Gene Action. Advance in Cancer Research 10: 1-81.
  20. Alfred LJ and Gelboin HV (1967) Benzypyrene Hydroxylase Induction by Polycyclic Hydrocarbons in Hamster Embryonic Cells Grown In Vitro. Science 157(3784): 75-76.
  21. Loeb LA and Gelboin HV (1963) Stimulation of Amino-Acid Incorporation by Nuclear Ribonucleic Acid from Normal and Methylcholanthrene Treated Rats. Nature 199(4895): 809-810.
  22. Gelboin H, Miller JA, and Miller EC (1959) The In Vitro Formation of Protein-Bound Derivatives of Aminoazo Dyes by Rat Liver Preparations. Cancer Research 19(9): 975-985.
National Library of Medicine On-Line Publication List (with abstracts)

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Last revised on August 21, 2002 by Linda Byrd