BIOGRAPHICAL SKETCH

A. Positions and honors

Professional Experience

1968-1971     Assist. Professor of Pharmacology, Yale University School of Medicine, New Haven, CT

1971-1978     Assoc. Professor of Pharmacology, Yale University School of Medicine, New Haven, CT

1978-1987     Professor and Head, Dept. of Pharmacology, Univ. of Connecticut Health Center, CT

1987- 2007     Professor, Dept. of Pharmacology, Univ. of Connecticut Health Center, Farmington, CT

2007- Present  Professor, Dept. of Cell Biology, Univ. of Connecticut Health Center, Farmington, CT

 

GRADUATE STUDENTS TRAINED:

1976 Ingela Jansson, Ph.D. University of Stockholm, Department of Biochemistry.

1977 Kathy Robie Suh, Ph.D. Yale University School of Medicine, Department of Pharmacology.

1983 Kuo-Chi Cheng, Ph.D. University of CT Health Center, Department of Pharmacology

1987 Leonard V. Favreau, Ph.D. University of CT Health Center, Department of Pharmacology.

1998 Mehregan Movasagh, M.Phil. University of Surrey, UK, Department of Biochemistry.

1999 Zhongqin Lu, Ph.D. Department of Chemistry, University of Connecticut, Storrs, Thesis committee.

2000 Carmelita Estavilla Department of Chemistry, University of Connecticut, Storrs, Thesis committee.

2001 Bernard Munge Department of Chemistry, University of Connecticut, Storrs, Thesis committee.

2001 Li Ping Zhou Department of Chemistry, University of Connecticut, Storrs, Thesis committee.

2001 Teresa Santiago Department of Molecular Microbiology, UCHC Thesis Committee.

2005 Besnik Bajrami Department of Chemistry, University of Connecticut, Storrs, Thesis committee.

2006 Nasreen Sultana Department of Chemistry, University of Connecticut , Storrs, M.S. Thesis committee.

2007 Minjeong So Department of Chemistry, University of Connecticut, Storrs, Associate Advisor.

2007 Sadagopan Krishnan Department of Chemistry, University of Connecticut,Storrs, Associate Advisor.

2007 Erwin Fundador Department of Chemistry, University of Connecticut, Storrs, Thesis committee.

 Awards and Other Professional Activities:

National Institutes of Health Research Career Development Awardee, 1971-1976.

Member, Pharmacology Study Section, NIH Division of Research Grants, 1974-1978.

Member, Pharmacological Sciences Review Committee, NIGMS, 1982-1986.

Member, National Board of Medical Examiners, FLEX 1 Subcommittee B, 1983-1985.

Member, Editorial and Advisory Board, Molecular Pharmacology, 1970-1991.

Member, Editorial and Advisory Board, Archives of Biochemistry and Biophysics, 1976-1983.

Member, Editorial and Advisory Board, The Journal of Biological Chemistry, 1983-1988.

Member, Editorial Board, Quarterly Reviews Drug Metabolism and Drug Interactions, 1981-

Associate Editor, Biochemical Pharmacology, 1975-1984.

Member, International Editorial Board, Drug Metabolism and Drug Interactions, 1988-Present

Associate Editor, Xenobiotica, 1994- Present.

Books Edited

Hepatic cytochrome P450 monooxygenase system.  John B. Schenkman and David Kupfer, editors.  756 pp. Pergamon Press, Publisher, 1982.

Molecular aspects of monooxygenases and bioactivation of toxic compounds.  Emel Arinç, John B. Schenkman and Ernest Hodgson, eds,  493 pp. NATO ASI Series A:  Life Sciences Vol. 202, Plenum Press, NY  (1991).

Cytochrome P450. , John Schenkman and Helmut Greim, eds, 739pp, Handbook of Experimental Pharmacology, Vol. 105, Springer-Verlag, NY, (1993).

Molecular aspects of oxidative drug-metabolizing enzymes. Emel Arinç, John B. Schenkman and Ernest Hodgson, eds, 495 pp., NATO ASI Series H, Vol. 90, Springer Verlag, NY, (1995).

Molecular and Applied Aspects of Oxidative Drug Metabolizing Enzymes, E. Arinç, J.B. Schenkman and E. Hodgson, eds.294 pp, NATO ASI Series H, Vol. 303, Plenum Publishing Corp., New York (1999).

Drug Metabolism Reviews 38(1), J.B. Schenkman, Guest Editor, 352pp. A volume dedicated to the memory of Dr. David Kupfer, Ph.D. (2006)

B. Relevant Publications (From list of more than 160 full length papers)

D. Choudhary, I. Jansson, M. Sarfarazi and J. B. Schenkman. Characterization of the biochemical and structural phenotypes of four CYP1B1 mutations observed in individuals with primary congenital glaucoma. Pharmacogenetics genom. In Press.

E.V. Fundador, D. Choudhary, J.B. Schenkman, and J.F. Rusling. Accurate DNA fragment sizing by capillary electrophoresis with laser-induced fluorescence array for detection of sequence specificity of DNA damage. Anal. Chem. 80:2212-2221 (2008).

J.R. Rusling, E.G. Hvastkovs, D.O. Hull, and J.B. Schenkman. Biochemical applications of ultrathin films of enzymes, polyions and DNA. Chem. Commun. 141-154 (2008).

B. Bajrami, E.G. Hvastkovs, G.C. Jensen, J.B. Schenkman and J.F. Rusling. Enzyme-DNA biocolloids for DNA adduct and reactive metabolite detection by chromatography-mass spectrometry. Anal. Chem. 80:922-932 (2008).

M. So, E.G. Hvastkovs, B. Bajrami, J.B. Schenkman and J.F.Rusling. Electrochemical genotoxicity screening for arylamines bioactivated by N-acetyltransferase. Anal. Chem. 80:1192-1200 (2008).

D. Choudhary, I. Jansson, K. Rezaul, D.K.M. Han M., Sarfarazi and J.B. Schenkman. Cyp1b1 protein in the mouse eye during development: An immunohistochemical study. Drug Metab. Dispos. 35:987-994 (2007).

J. F. Rusling, E. G. Hvastkovs and J. B. Schenkman. Toxicity screening with biosensors that measure DNA damage. Curr. Opin. Drug Disc. & Devel. 10:67-73 (2007).

E.G. Hvastkovs, M. So, S. Krishnan, B. Bajrami, M. Tarun, I. Jansson, J.B. Schenkman, and J.F. Rusling. Electrochemiluminescent arrays for cytochrome P450-activated genotoxicity screening. Damage from benzo[a]pyrene metabolites. Anal. Chem. 79:1897-1906 (2007).

D. Choudhary, I. Jansson, M. Sarfarazi and J.B. Schenkman. Physiological Significance and Expression of P450s in the developing eye. Drug Metabolism Reviews 38:337-352 (2006).

D. Choudhary, I. Jansson, I. Stoilov, M. Sarfarazi, and J.B. Schenkman. Expression patterns of mouse and human CYP orthologs (families 1-4) during development and in different adult tissues. Arch. Biochem. Biophys. 436:50-61 (2005).

B. Wang, I. Jansson, J. B. Schenkman and J. F. Rusling. Detecting enzymes that generate genotoxic benzo[a]pyrene metabolites using sensor arrays. Anal. Chem. 37:1361-1367. (2005).

N. Sultana, J. B. Schenkman, and J. F. Rusling. Protein film electrochemistry of microsomes genetically enriched in human cytochrome P450 monooxygenases. J. Am. Chem. Soc. 127:13460-13461 (2005)

I. Stoilov, T. Razie, I. Jansson, J. B. Schenkman and M. Sarfarazi. Expression of cytochrome P4501b1 (Cyp1b1) during early mouse development. Mol. Vision 10: 629-636 (2004).

D. Choudhary, I. Jansson, I. Stoilov, M. Sarfarazi and J. B. Schenkman. Metabolism of retinoids and arachidonic acid by human and mouse cytochrome P450 1B1. Drug Metab. Dispos. 32: 840-867 (2004).

D. Choudhary., I. Jansson, J.B. Schenkman, M Sarfarazi., and I Stoilov. Comparative expression profiling of 40 mouse cytochrome p450 genes in embryonic and adult tissues. Arch Biochem. Biophys. 414: 91-100 (2003).

C. Estavillo, Z. Lu, I. Jansson, J.B. Schenkman and J.F. Rusling. Epoxidation of styrene by human cyt P450 1A2 by thin film electrolyis and peroxide activation compared to solution reactions. Biophys. Chem. 104:291-296 (2003).

B. Munge, C. Estavillo, J.B. Schenkman and J.R. Rusling. Optimization of electrochemical and peroxide-driven oxidation of styrene with ultrathin polyion films containing P450_cam and myoglobin. ChemBiochem. 4: 82-89 (2003).

L. Zhou, J. Yang, C. Estavillo, J.D. Stuart, J.B. Schenkman, and J.R. Rusling. Toxicity screening by electrochemical detection of DNA damage by metabolites generated In-situ in ultrathin DNA-enzyme films. J. Am. Chem. Soc. 125:1431-1438 (2003).

I. Jansson, I. Stoilov, M. Sarfarazi and J.B. Schenkman. Effect of two mutations of human CYP1B1, G61E and R469W, on stability and endogenous steroid substrate metabolism. Pharmacogenetics 11:1-9 (2001).

J.B. Schenkman, I. Jansson, Y. Lvov, J.F. Rusling, S. Boussaad, and N.J. Tao. Charge-dependent sidedness of cytochrome P450 forms studied by quartz crystal microbalance and atomic force microscopy. Arch. Biochem. Biophys. 385:78-87 (2001).

I. Stoilov, I. Jansson, M. Sarfarazi, and J.B. Schenkman. Roles of cytochrome P450 in development. Drug Metab. Drug Interac. 18: 1-23 (2001).

I. Jansson, I. Stoilov, M. Sarfarazi and J.B. Schenkman. Effect of two mutations of human CYP1B1, G61E  and R469W, on stability and endogenous steroid substrate metabolism. Pharmacogenetics 11:1-9 (2001).

I. Jansson, I. Stoilov, M. Sarfarazi, and J.B. Schenkman. Enhanced expression of CYP1B1 in E. coli. Toxicology, 144:211-219 (2000).

 Z. Lu, Y. Lvov, I. Jansson, J. B. Schenkman, and J. F. Rusling,  "Electroactive Films of Alternately Layered Polycations and Iron-sulfur Protein Putidaredoxin on Gold", J. Coll. Interface Science 224:162-168 (2000).)

X. Zu, Z. Lu, Z. Zhang, J.B. Schenkman, and J.F. Rusling "Electro-enzyme Catalyzed Oxidation of Styrene and Cis-b-Methylstyrene using Thin Films of Cytochrome P450cam and Myoglobin" Langmuir 15,7372-7377, (1999).

J.B. Schenkman and I. Jansson. Interactions between cytochrome P450 and cytochrome b₅. Drug Metab. Rev. 31:351-364 (1999).

Y.M. Lvov, Z. Lu, J.B. Schenkman, and J.F. Rusling. Direct electrochemistry of myoglobin and cytochrome P450cam in alternate polyion layer-by-layer films. J. Chem. Soc. 120:4073-4080 (1998).

 Z. Zhang, A.-E. F. Nassar, Z. Lu, J.B. Schenkman, and J.F. Rusling. Direct Electron Injection from Electrodes to Cytochrome P450cam in Biomembrane-like Films. J. Chem. Soc. Faraday Trans., 93:1769-1774 (1997).

 I. Jansson and J.B. Schenkman. Substrate influence on the interaction between cytochrome P450 and cytochrome b₅ in microsomes. Arch. Biochem. Biophys. 325:265-269 (1996).

 I. Jansson, J.E. Mole and J.B. Schenkman. The isolation and comparison of multiple forms of CYP2B from untreated and phenobarbital-treated rabbit liver microsomes. Arch. Biochem. Biophys. 316:275-284 (1995).

 J.B. Schenkman and A.I. Voznesensky. Interaction between cytochrome P450 and reductase. pp.47-63 in ASI Series H, Vol. 90, Molecular aspects of Oxidative Drug-Metabolizing Enzymes, E. Arinç, J.B. Schenkman and E. Hodgson, eds., Springer-Verlag, Berlin (1995).

 J.B. Schenkman, A.I. Voznesensky and I. Jansson. Influence of ionic strength on the P450 monooxygenase reaction and role of cytochrome b₅ in the process. Arch. Biochem. Biophys. 314:234-241 (1994).

 A.I. Voznesensky, J.B. Schenkman, S.J. Pernecky and M.J. Coon. The NH₂-terminal region of rabbit CYP2E1 is not essential for the interaction with NADPH-cytochrome P450 reductase. Biochem. Biophys. Res. Commun. 203:156-161 (1994).

 A.I. Voznesensky and J.B. Schenkman. Quantitative analyses of electrostatic interactions between NADPH-cytochrome P450 reductase and cytochrome P450 enzymes. J. Biol. Chem. 269:15724-15731 (1994).

 J.B. Schenkman, Protein-Protein Interactions, in Cytochrome P-450, pp. 527-545, J.B. Schenkman and H. Greim, eds., Springer-Verlag, NY (1993).

 A.I. Voznesensky and J.B. Schenkman. Inhibition of cytochrome P450 reductase by polyols has an electrostatic nature. Eur. J. Biochem. 210:741-746 (1992).

 T.H. Richardson, J.B. Schenkman, R. Turcan, P.S. Goldfarb and G.G. Gibson. Molecular cloning of a cDNA for rat diabetes-inducible cytochrome P-450 RLM6: Horomonal regulation and similarity to the cytochrome P-450 2E1 gene.  Xenobiotica 22:621-631 (1992).

 A.I. Voznesensky and J.B. Schenkman. The cytochrome P-450 2B4-NADPH-Cytochrome P-450 reductase electron transfer complex is not formed by charge pairing. J. Biol. Chem. 267:14669-14676 (1992).

 W. Cammer, M. Downing, W. Clarke and J.B. Schenkman. Immunochemical staining of the RLM6 form of cytochrome P-450 in oligodendrocytes and myelin of rat brain. J. Histochem. Cytochem. 39, 1089-1094 (1991).

 I. Jansson, M. Curti, P.M. Epstein, J.A. Peterson and J.B. Schenkman. Relationship between phosphorylation and cytochrome P450 destruction. Arch. Biochem. Biophys. 282:285-292 (1990).

 P.M. Epstein, M. Curti, I. Jansson, C-K Huang and J.B. Schenkman. Phosphorylation of cytochrome P450: Regulation by cytochrome b₅. Arch. Biochem. Biophys. 271: 424-432 (1989).

I. Jansson, P.M. Epstein, S. Bains and J.B. Schenkman. Inverse relationship between cytochrome P450 phosphorylation and complexation with cytochrome b₅. Arch. Biochem. Biophys. 259: 441-448 (1987).

 I. Jansson and J.B. Schenkman. Influence of cytochrome b₅ on the stoichiometry of the different oxidative reactions catalyzed by liver microsomal cytochrome P450. Drug Metab. Dispos. 15:344-348 (1987).

 P.P. Tamburini and J.B. Schenkman. Purification to homogeneity and enzymological characterization of a functional covalent complex containing rabbit liver cytochromes P-450 LM2 and b₅.  Proc. Natl. Acad. Sci. USA, 84: 11-15 (1987).

 P.P. Tamburini and J.B. Schenkman. Differences in the mechanism of functional interaction between NADPH-cytochrome P450 reductase and its redox partners. Mol. Pharmacol. 30:178-185 (1986).

 P.P. Tamburini and J.B. Schenkman. Mechanism of interaction between cytochromes P450 RLM5 and b₅: Evidence for an electrostatic mechanism involving cytochrome b₅ heme propionate groups. Arch. Biochem. Biophys. 245:512-522 (1986).

 

C. Ongoing Research Support

 

R01 EY11095, (2006-2011) “Molecular Genetics of Primary Congenital Glaucoma.” P.I., M. Sarfarazi, Co-P.I., J.B. Schenkman. With support from this grant we have been able to prepare the CYP1B1 cDNA, amplify it and prepare wild-type and mutant cDNA with 5’- and 3’-restriction enzyme sites needed for insertion into a pCWori expression vector. In this way CYP1B1 and mutations seen in the disease phenotype of congenital glaucoma have been produced for study of the effects of the mutations on the biochemical properties of the hemoproteins. Our studies have provided a potential explanation for the incomplete penetrance that results from the homozygous mutant genotype in families with the primary congenital glaucoma phenotype. In this study we have been examining and comparing metabolism of endobiotics by human and mouse orthologous forms of CYP1B1.

 

R01 ES03154 (2004-2008), P.I. James F. Rusling. “Electrocatalytic studies of toxic pollutant activation.” Dr. Schenkman is an Investigator on this grant with a subcontract, "P450 expression and quantifying electrochemical DNA damage". The goal of his study is to examine the topology of the cytochrome P450 and identify sites for the docking and electron transfer between redox partners in the monooxygenase reactions. We have been using quartz crystal microbalance spectroscopy (QCM) and atomic force microscopy (AFM) as tools in this study and have been attempting to also develop functional biosensors and biocatalysts using the cytochrome P450 monooxygenase forms and these systems. The study also involves determination of the nature of cytochrome P450 metabolite reactive 'hot spots' of attack on DNA. The nucleotide bases in these 'hot spots' have some sort of predilection for reaction with certain electrophilic metabolites of cytochrome P450, possibly making some genes predictable targets.