CURRICULUM VITAE
Address:
JOHN A. THOMPSON
Department of Pharmaceutical Sciences
School of Pharmacy, Box C238
University of Colorado Health Sciences Center
Denver, Colorado 80262
Office: 303-315-6167, Fax: 303-315-0274
Email: john.thompson@uchsc.edu
Education
Clark University, Worcester, MA
University of California, Los Angeles
B.A., Chemistry, 1964
Ph.D., Organic Chemistry, 1969
Professional Experience
1988 - present
Professor of Medicinal Chemistry, Department of Pharmaceutical
Sciences, School of Pharmacy, University of Colorado
Health Sciences Center, Denver
1997 - 98
Visiting Scholar (sabbatical), National Jewish Res. and Medical Center,
Denver, CO (9/97-4/98) and Department of Medicinal Chemistry,
University of Washington, Seattle (5/98-7/98)
1990 - 91
Visiting Scientist, Division of Biochemistry and Molecular Biology,
University of California, Berkeley (sabbatical)
1982 - 88
Associate Professor, Division of Pharmaceutical Sciences, School of
Pharmacy, University of Colorado, Boulder
1983 - 84
Visiting Associate Professor, Department of Pharmaceutical Chemistry,
School of Pharmacy, University of California, San Francisco
(sabbatical)
1977 - 82
Assistant Professor, Division of Pharmaceutical Sciences, School of
Pharmacy, University of Colorado, Boulder
1973 - 76
Senior Research Associate, Departments of Pharmacology and Pediatrics,
University of Colorado Health Sciences Center, Denver
1972 - 73
Assistant Professor (Adjunct), Department of Medicinal Chemistry,
University of Minnesota, Minneapolis
1971 - 73
Research Chemist, Clinical Pharmacology Division,
Veterans Administration Medical Center, Minneapolis
1970 - 71
Postdoctoral Fellow, Syntex Laboratories, Mexico City, Mexico
1969 - 70
Postdoctoral Fellow, Department of Chemistry
University of California, Irvine
Professional Honors/Activities
Chemical Pathology Study Section, NIH, Regular Member (1990-94)
Ad Hoc Service on NIH Study Sections:
Special Review Groups on Cancer Chemoprevention, NCI (1986-90)
Site Visit-Johns Hopkins University (10/86)
Toxicology Study Section (10/88)
Site Visit-University of Illinois (3/89)
Pharmacology Study Section (6/89)
Site Visit-University of Texas, Galveston (9/93)
Site Visit-University of Louisiana (4/94)
Oncological Sciences Special Emphasis Review Panel (11/95)
Medical Research Council of Canada, external reviewer (11/93)
U.S. Army Medical Research, Breast Cancer Research Review Panel (9/96)
Executive Committee, Drug Metabolism Division of ASPET (1991-93)
Program Committee, Division of Chemical Toxicology, ACS (1997-present)
Editorial advisory boards:
Drug Metabolism and Disposition (1988-91)
Chemical Research in Toxicology (1988-91, 2003-06)
Ad Hoc Reviewer:
Drug Metabolism and Disposition
Chemical Research in Toxicology
Biochemistry
Toxicology and Applied Pharmacology
Xenobiotica
Chemico-Biological Interactions
Journal of Pharmacology and Experimental Therapeutics
Journal of Medicinal Chemistry
Symposia Organized and Chaired:
American Chemical Society, "Free Radicals in Bioorganic Chemistry,"
Denver, 1986.
American Society for Pharmacology and Experimental Therapeutics,
"Molecular Pharmacology of Hydroperoxides," Montreal, 1988.
Gordon Research Conference, "Role of Peroxidases in Drug Metabolism,"
Plymouth, NH, 1991.
American Chemical Society, “Antioxidants in Toxicology, ”
Anaheim, 1999
Memberships in Professional Societies and Research Centers/Programs:
American Chemical Society, Medicinal Chemistry and Chemical Toxicology Sections
American Society for Pharmacology and Experimental Therapeutics
Society of Toxicology, Mechanisms Division
International Society for the Study of Xenobiotics
University of Colorado Cancer Center
Hepatobiliary Research Center, University of Colorado
Molecular Toxicology and Environmental Health Sciences Center, Univ. of Colorado
Medical Scientist (M.D./Ph.D.) Training Program, University of Colorado
Faculty Research Fellowship, Chemex Pharmaceuticals (1986-88)
Postdoctoral Research Fellowship, Syntex Corporation (1970-71)
B.A. degree awarded with Honors in Chemistry, Clark University, 1964
NSF-URP Program, Dept. of Chemistry, Clark University, 1962-64.
Grants (past 10 years)
"Formation and Reactivity of Toxic Quinone Methides," NIH (RO1-ES06216), Principal
Investigator, 4/94-3/98.
“Acquisition of an Electrospray Tandem Mass Spectrometer,” NIH (S10-RR12974), Principal
Investigator, 5/98-4/99.
"Bioactivation of Dietary Phenols by Hemoproteins," NIH (R01-CA41248), Principal
Investigator, 3/86-8/08.
“Acquisition of an Ion Trap Mass Spectrometer,” NSF (MRI0321301)
“Prostate Cancer Prevention by Procyanidins in Grape Seed Extract,” NIH (RO1-CA91883), CoInvestigator (C. Agarwal, PI), 1/02-07/12.
Invited Presentations (past 10 years)
Chemical Toxicology Division of the Amercian Chemical Society, Symposium on Antioxidants
in Toxicology, “Reactive Metabolites of Phenolic Antioxidants” (3/99)
Department of Chemistry, Colorado School of Mines, "Reactive Metabolites of Phenolic Antioxidants:
Formation and Toxicity" (2/99)
Chemical Toxicology Division of the American Chemical Society, Symposium on Antioxidants
in Toxicology, “Reactive Metabolites of Phenolic Antioxidants” (3/99)
6th International ISSX Meeting, Munich, Germany, “BHT Metabolites and Mechanisms of Lung
Tumorigenesis” (10/01)
Colorado Oxgyen Radical Society, “Roles of Hemoproteins in the Metabolism and Toxicity of
Phenolic Antioxidants” (2/03).
Publications (past 10 years)
Mancini, J.A., Waugh, R.J., Thompson, J.A., Evans, J F., Zamboni, R., and Murphy, R.C.
Structural characterization of the covalent attachment of leukotriene A3 to leukotriene A4
hydrolase. Arch. Biochem. Biophys., 354: 117-124 (1998).
Desjardins, J. P., Beard, S. E., Mapoles, J. E., Gee, P., and Thompson, J. A., Transcriptional
Activity of Quinone Methides Derived from the tumor promoter butylated hydroxytoluene
in HepG2 cells. Cancer Lett., 131/2: 201-207 (1998).
Dwyer-Nield, L.D., Thompson, J.A., Peljak, G., Barker, T.D., Parkinson, A., Cohen, J.J.,
Dinsdale, D., and Malkinson, A.M., Induction of Apoptosis in Mouse and Human Lung
Epithelial Cells by a Metabolite of Butylated Hydroxytoluene. Toxicology , 130: 115-127
(1998).
Thompson, J. A., Carlson, T. J., Sun, Y., Dwyer-Nield, L. D., and Malkinson, A. M. Studies
using structural analogs and inbred strain differences to support a role for quinone methide
metabolites of butylated hydroxytoluene in mouse lung tumor promotion. Toxicology 160:
197-205 (2001).
Kupfer, R., Liu, S.Y., Allentoff, A.J., and Thompson, J.A. Comparisons of hydroperoxide
isomerase and monooxygenase activities of cytochrome P450 for conversions of allylic
hydroperoxides and alcohols to epoxyalcohols and diols: probing substrate reorientation in
the active site. Biochemistry 40: 11490-11501(2001).
Kupfer, R., Dwyer-Nield, L.D., Malkinson, A.M., and Thompson, J.A. Lung toxicity and
tumor promotion by hydroxylated derivatives of 2,6-di-tert-butyl-4-methylphenol (BHT)
and 2-tert-butyl-4-methyl-6-iso-propylphenol: correlation with quinone methide reactivity.
Chem. Res. Toxicol. 15: 1106-1112. (2002).
Sun, Y., Dwyer-Nield, L.D., Malkinson, A.M., Zhang, Y.L., and Thompson, J.A. Responses of
tumorigenic and non-tumorigenic mouse lung epithelial cell lines to electrophilic
metabolites of the tumor promoter butylated hydroxytoluene. Chem.-Biol. Interactions
145: 41-51 (2003).
Lemercier, J.-N., Meier, B.W., Gomez, J.D., and Thompson, J.A. Inhibition of glutathione Stransferase P1-1 in mouse lung epithelial cells by the tumor promoter 2,6-di-tert-butyl-4methylene-2,5-cyclohexadienone (BHT-quinone methide): protein adducts investigated by
electrospray mass spectrometry. Chem. Res. Toxicol. 17: 1675-1683. (2004).
Meier, B.W., Gomez, J.D., Zhou, A., and Thompson, J.A. Immunochemical and proteomic
analysis of covalent adducts formed by quinone methide tumor promoters in mouse lung
epithelial cell lines. Chem. Res. Toxicol. 18: 1575-1585. (2005).
Veluri, R., Singh, R.P., Liu, Z., Thompson, J.A., Agarwal, R., and Agarwal, C. Fractionation of
grape seed extract and identification of gallic acid as one of the major active constituents
causing growth inhibition and apoptotic death of DU145 human prostate carcinoma cells.
Carcinogenesis, 27: 1445-1453 (2006).
Meier, B., Gomez, J.D., Kirichenko, O., and Thompson, J.A. Mechanistic basis for
inflammation and tumor promotion in lungs of 2,6-di-tert-butyl-4-methylphenol-treated
mice: electrophilic metabolites alkylate and inactivate antioxidant enzymes. Chem. Res.
Toxicol., 20: 199-207 (2007).
Agarwal, C., Veluri, R., Kaur, M., Chou, S.-C., Thompson, J.A., and Agarwal, R. Fractionation
of high molecular weight tannins in grape seed extract and identification of procyanidin B23,3’-di-O-gallate as a major active constituent causing growth inhibition and apoptotic
death of DU145 prostate carcinoma cells. Carcinogenesis, 28:1478-1484 (2007).
Shearn, C.T., Fritz, K.S., Meier, B.W., Kirichenko, O.V. and Thompson, J.A. Carbonyl reductase
inactivation may contribute to mouse lung tumor promotion by electrophilic metabolites of
butylated hydroxytoluene: protein alkylation in vivo and in vitro. Chem. Res. Toxicol. 21: 16311641 (2008).
Thompson, J.A. and Bolton, J.L., Formation and reactions of xenobiotic quinone methides in biology. In:
Reactive Intermediates in Chemistry and Biology, Vol 1: Quinone Methides, S.E. Rokita, ed., John
Wiley & Sons, New York (2009).
Meeting Presentations:
Estrogen-Derived Hydroperoxides. 7th North American ISSX Meeting, October 1996.
Lewis, M.A., Qian, M., and Thompson, J.A., Influences of structure and reactivity on the binding
of quinone methides to DNA. American Chemical Society National Meeting, April, 1997.
Desjardins, J.P., Beard, S.E., Mapoles, J.E., and Thompson, J.A., Gene induction in human
hepatoma HepG2 cells by Electrophilic Quinoid Metabolites. 8th North American ISSX
Meeting, October 1997.
Lemercier, J.-N., Carlson, T.J., and Thompson, J.A., Formation and Detection of Methionine
Sulfoxide Residues in Peptides and Proteins. American Chemical Society National
Meeting, August 1998.
Kupfer, R, Allentoff, A.J., and Thompson, J.A., Stereoselective Epoxidation of Quinols by
Cytochrome P450 2E1. American Chemical Society National Meeting, August 1998.
Desjardins, J.P., Lemercier, J.-N., and Thompson, J.A., Quinone Methides Induce Genes and
Inhibit Glutathione S-Transferase in HepG2 Cells. 5th International ISSX Meeting,
October 1998.
Lemercier, J.-N., Desjardins, J.P., and Thompson, J.A., Inhibition of Glutatione S-Transferases
by Metabolites of Butylated Hydroxytoluene. Society of Toxicology, 38th Annual
Meeting, March, 1999.
Thompson, J.A., Kupfer, R., and Allentoff, A.J., Reactive Metabolites of Phenolic Antioxidants.
American Chemical Society National Meeting, March, 1999.
Kupfer, R., Sun, Y., Malkinson, A.M., and Thompson, J.A., Quinone Methides from a Phenolic
Tumor promoter are selectively toxic in cell lines derived from normal vs. neoplastic mouse
lung epithelium. 9th North American Meeting of the International Society for the Study of
Xenobiotics, October, 1999.
Sun, Y., Kupfer, R., Lemercier, J.N., and Thompson, J.A., Effects of Quione Methides in Mouse
Lung Epithelial Cell Lines. Toxicologist 54, 49 (2000).
Lemercier, J.-N., Sun, Y., and Thompson, J.A., Characterization of Glutathione S-Transferase
Isoforms and Electrophile-Induced Inactivation in Normal and Transformed Murine Lung
Cells by Electrospray LC-MS-MS. 48th ASMS Conference on Mass Spectrometry and
Allied Topics, June, 2000.
Sun, Y., Lemercier, J.N., and Thompson, J.A., Oxidative Stress and Apoptosis in Mouse Lung
Cells Exposed to a Quione Methide Tumor Promoter. Toxicologist 60, 118 (2001).
Thompson, J.A., Sun, Y., Lemercier, J.-N., and Wilmore, B., BHT Metabolites and Mechanisms
of Lung Tumorigenesis. Drug Metab. Revs. 33(s), 23 (2001).
Meier, B., Gomez, J,, and Thompson, J.A. Immunochemical Detection and Mass Spectrometric
Identification of BHT-Protein Adducts in Mouse Lung Cells. Drug Metab. Revs. 36, 223
(2004).
Agarwal, C. Veluri, R., Thompson, J.A., and Agarwal, R., Biofractionation of GSE: Identification
of Gallic Acid as One of the Major Active Constituents Causing Growth Inhibition and
Apoptotic Death of DU145 Human Prostate Carcinoma Cells. American Association for
Cancer Research Annual Meeting, April, 2005.
Gomez, J., Meier, B., and Thompson, J.A. Identifying Alkylated Proteins by Immunochemistry
and Mass Spectrometry in Mouse Lung Tissues Exposed to Electrophilic Tumor Promoters.
53rd ASMS Conference on Mass Spectrometry and Allied Topics, June, 2005.
Veluri, R., Thompson, J.A., Agarwal, R., and Agarwal, C. LC/MS Identification of Gallic Acid
and Procyanidins from Grape Seeds with Anti-cancer Activity in DU145 Human Prostate
Carcinoma Cells. American Chemical Society National Meeting, August, 2005.
Kirichenko, O.V., Meier, B.W., Gomez, J.D., and Thompson, J.A. ESI- and MALDI-MS studies
of covalently modified peroxiredoxin and superoxide dismutase: targets of quinone methide
lung tumor promoters. 54th ASMS Conference on Mass Spectrometry and Allied Topics,
May, 2006.
Kirichenko, O.V., Shearn, C.T., Meier, B.W., and Thompson, J.A. Mass spectrometric studies of
isolated recombinant mouse lung carbonyl reductase alkylated by quinone methide tumor
promoters. Drug Metab. Revs. 39 (2007).
Shearn, C.T. and Thompson, J.A. Protein damage from oxidative stress accumulates in lungs of mice
exposed to electrophilic tumor promoters derived from BHT. Society of Toxicology, 47th Annual
Meeting, March (2008).
Fritz, K., Shearn, C., Gomez, J., and Thompson, J.A. MALDI/TOFiIdentification of alkylation sites in
recombinant carbonyl reductase inactivated by electrophilic metabolites of a lung tumor prommoter.
56th ASMS Conference on Mass Spectrometry and Allied Topics, June, 2008.
Katayama, J., Roberts, A., Kaspera, R., LeTrong, I, Stenkamp, R., Thompson, J.A. and Totah, R.A.
Homolytic verses heterolytic cleavage of the oxygen-oxygen bond in CYP BM3 and the variants
F87A and T268A. Drug Metab. Revs. 40(s), 77-78 (2008).