Robert L. Haining, Ph.D. Assistant Professor Department of Basic Pharmaceutical Sciences West Virginia University P.O. Box 9530 Morgantown, WV 26506-9530 Phone: (304) 293-1450 Fax: (304) 293-2576 E-Mail: rhaining@hsc.wvu.edu

Education:

Graduate Training

M.S. (Biochemistry), Washington State University, Pullman Washington, December 1990
Ph.D. (Biochemistry), Washington State University, August 1993

Undergraduate Training

B.A. (Chemistry), Whitman College, Walla Walla, Washington, May 1986

Research Interests:

* Molecular Biology
* Baculovirus-mediated expression
* Protein purification
* Metabolite Analysis (GC-MS, HPLC)
* Enzyme kinetics
* Enzyme structure/function

Publications:

2003

Haining, R.L. and Yu, A. (2003) Cytochrome P450 Pharmacogenetics, in Cytochrome P450 and Drug Metabolism, J Lee, Ed., FontisMedia, pp. 343-387.

Yu, A., Granvil, C.P., Haining, R.L., Krausz, K., Corchero, J., Kupfer, A., Idle, J.R. and Gonzalez, F.J. (2003) The relative contribution of monoamine oxidase and cytochromes P450 isozymes to the metabolic deamination of the trace amine tryptamine. J.Pharm.Exp.Ther. 304:539-546.

2002

Y u, A., Kneller, B., Rettie, A.E., and Haining, R.L.(2002) Expression, Purification, Biochemical Characterization and Comparative Function of Human Cytochrome P450 2D6.1, 2D6.2, 2D6.10 and 2D6.17 Allelic Isoforms J.Pharm.Exp.Ther. 303:1291-1300.

Ramamoorthy, Y., Yu, A., Suh, N., Haining, R.L., Tyndale, R.F., and Sellers, E.M. (2002) Reduced (+/-)-3,4-methylenedioxymethamphetamine ("Ecstasy") metabolism with cytochrome P450 2D6 inhibitors and pharmacogenetic variants in vitro. Biochem. Pharmacol. 63:2111-9.

Tracy, T.S., Hutzler, J.M., Haining, R.L., Rettie, A.E., Hummel, M.A., and Dickmann, L.J. (2002) Polymorphic variants (CYP2C9*3 and CYP2C9*5) and the F114L active site mutation of CYP2C9: effect on atypical kinetic metabolism profiles. Drug Metab.Dispos. 30: 385-90.

Suzuki, H., Kneller, B. M., Haining, R.L., Trager, W. F. and Rettie, A. E. (2002) (+)-N-3-Benzyl Nirvanol and (-)-N-3-Benzyl-Phenobarbitol: New Potent and Selective In Vitro Inhibitors of CYP2C19. Drug Metab.Dispos. 30: 235-9.

2001

Suzuki, H., Kneller, B. M., Haining, R.L., Trager, W. F. and Rettie, A. E. (In press Dec. 2001) (+)-N-3-Benzyl-Nirvanol and (-)-N-3-Benzyl-Phenobarbitol: New Potent and Selective In Vitro Inhibitors of CYP2C19. Drug Metabolism and Disposition.

Yu, A., Dong, H., Lang, D. and Haining, R.L. (2001) Characterization of   Dextromethorphan O- and N-Demethylation Catalyzed by Highly Purified Recombinant Human CYP2D6. Drug Metabolism and Disposition 29: 1362-1365.

Yu, A. and Haining, R.L. (2001) Comparative Contribution to Dextromethorphan Metabolism by Cytochrome P450 Isoforms in Vitro: Can Dextromethorphan Be Used as a Dual Probe for Both CYP2D6 and CYP3A Activities? Drug Metabolism and Disposition 29: 1514-1520.

Kilicarslan T., Haining, R.L., Rettie A.E., Busto U., Tyndale R. F. and Sellers E.M. (2001) Flunitrazepam metabolism by cytochrome P450s 2C19 and 3A4.Drug Metabolism and Disposition 29: 460-465.

2000

Dong, H., Haining, R.L., Thummel, K. E., Rettie, A. E. and Nelson, S. D. (2000) Involvement of human cytochrome P450 2D6 in the bioactivation of acetaminophen.Drug Metabolism and Disposition 28: 1397-1400.

Rettie, A. E., Koop, D. R. and Haining, R.L.. Human CYP2C enzymes. In: Metabolic Drug Interactions (2000), Lippincott Williams & Wilkins, Philadelphia, PA., pp. 75 -86.

1999

Rettie, A. E., Haining, R.L., Bajpai, M., and Levy, R. H. (1999) A common genetic basis for idiosyncratic toxicity of warfarin and phenytoin. Epilepsy Research 35: 253-255.

Haining, R.L., Jones, J. P., Henne, K. R., Fisher, M.B., Trager, W. F. and Rettie, A. E. (1999) Enzymatic determinants of the substrate specificity of CYP2C9: Role of B’-C loop residues in providing the pi-stacking anchor site for warfarin binding. Biochemistry 38: 3285-3292.

Koenigs, L. L., Peter, R. M., Hunter, A. P., Haining, R.L., Rettie, A. E., Friedberg, T.,Pritchard, M. P., Shou, M., Rushmore, T. H., and Trager, W. F. (1999) Electrospray ionization mass spectrometric analysis of intact cytochrome P450: Identification of tienilic acid adducts to P450 2C9. Biochemistry 38: 2312-2319.

1997

Haining, R.L., Hunter, A. P., Sadeque, A. J. M., Philpot, R. M. and Rettie, A. E. (1997) Baculovirus-mediated expression and purification of human FMO3: catalytic, immunochemical, and structural characterization. Drug Metabolism and Disposition 25: 790-797.

Steward, D. J., Haining, R.L., Henne, K. R., Davis, G., Rushmore, T. H., Trager, W. F. and Rettie, A. E. (1997) Genetic association between sensitivity to warfarin and expression of CYP2C9*3. Pharmacogenetics 7: 361-367.

Tugnait, M., Hawes, E. M., McKay, G., Rettie, A. E., Haining, R.L. and Midha, K. K. (1997) N-oxygenation of clozapine by flavin-containing monooxygenase. Drug Metabolism and Disposition 25: 524-527.

1996

Haining, R.L., Hunter, A. P., Veronese, M. E., Trager, W. F. and Rettie, A. E.(1996) Allelic variants of human cytochrome P-450 2C9: baculovirus-mediated expression, purification, structural characterization, substrate stereoselectivity, and prochiral selectivity of the wild-type and I359L mutant forms. Archives of Biochemistry and Biophysics 333: 447-458.

1994

Haining, R.L. and McFadden, B. A. (1994) Active-site histidines in recombinant cyanobacterial ribulose-1,5-bisphosphate carboxylase-oxygenase examined by site-directed mutagenesis. Photosynthesis Research 41: 349-356.

1990

Haining, R.L. and McFadden B. A. (1990) A critical arginine in the large subunit of ribulose bisphosphate carboxylase/oxygenase identified by site-directed mutagenesis. Journal of Biological Chemistry 265: 5434-5439.

Oral Presentations:

Purification, biochemical characterization and comparative enzyme kinetics of recombinant human CYP2D6*1 and CYP2D6*2. Presented at the Sixth International Symposium on Biological Reactive Intermediates, July 2000, Paris, France.

Correlation of the cytochrome P450 2C9 Leu-359 defect with warfarin sensitivity. Presented at the 17th International Congress of Biochemistry and Biology, August, 1997, San Francisco, California

Determinants of substrate and inhibitor specificity of human CYP2C9. Presented at the 7th North American ISSX Meeting, October 1996, San Diego, California.

Determinants of substrate and inhibitor specificity of human CYP2C9. Presented  at the Gordon Conference on Drug Metabolism, July 1996, Plymouth,New Hampshire.

Professional Experience:

9/86-5/87 Analytical Chemist, Olympic Scientific, Inc., Seattle, Washington (50% time).
11/86-5/87 Lab Technician, Department of Pharmacology, University of Washington, Seattle, WA
6/87-8/93 Graduate Student Research Associate, Washington State University, Pullman, WA.
9/93-12/93 Post Doctoral Research Associate, UCSF, San Francisco, California.
7/94-5/99 Post Doctoral Research Associate, Department of Medicinal Chemistry, UW Seattle.
5/99-8/00 Research Assistant Professor, Department of Medicinal Chemistry, UW.
8/00-present Assistant Professor, Dept. of Basic Pharmaceutical Sciences, WVU, Morgantown,WV

Awards:

First place in post-doctoral competition at the 7th North American ISSX Meeting, San Diego, California Oct.20-24,1996 "Determinants of substrate and inhibitor specificity of human CYP2C9".

NIEHS Grant: 1R01ES/AG09894-01 Functional effects of allelic variation in human CYP2D6. (RFA: Structure/function relationships of environmentally relevant genetic variants). 05/01/99-04/30/02.