BIOGRAPHICAL SKETCH

 

NAME

Wayne L. Backes

POSITION TITLE

Professor/Associate Dean for Research

 

EDUCATION/TRAINING

 

 

 

 

INSTITUTION AND LOCATION

DEGREE

YEAR(s)

FIELD OF STUDY

Western Maryland College, Westminster, MD

B.A.

1969-1973

Chemistry

West Virginia University, Morgantown, WV

Ph.D.

1974-1979

Biochemistry

Univ. of Connecticut Health Ctr., Farmington, CT

postdoctoral

1979-1981

Pharmacology

 

 

 

 

 A. Positions and Honors.

1981-Nov. 1983                Instructor of Pharmacology, Univ. Connecticut Health Center, Farmington, CT

Dec. 1983 - June 1984     Res. Asst. Prof. Dept. of Pharmacology, Univ. Conn. Health Ctr., Farmington, CT

July 1984 - July 1989       Assistant Professor, Dept. of Pharmacology, LSU Medical Center, New Orleans, LA

July 1989 - 1995               Associate Professor, Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center, New Orleans, LA

July 1995 - present           Professor, Dept. of Pharmacology, LSUHSC, New Orleans, LA

Jan. 1999 - 2001               Acting Head, Department of Pharmacology, LSUMC, New Orleans, LA

October 2001 – present    Associate Dean for Research, LSU Health Sciences Center, New Orleans, LA

July 2008 – present          Secretary-Treasurer for the Division for Toxicology (Division of ASPET)

Jan. 2009 – present          Xenobiotic and Nutrition Disposition and Action Study Section, National Institutes of Health

Jan. 2006 – present          External Advisory Committee, Center for the Study of Botanicals and Metabolic Syndrome., Pennington Biomedical Research Center and Rutgers University; NCCAM, January 2006 – present

 

B. Selected peer-reviewed publications (in chronological order). Do not include publications submitted or in preparation. (from 50 publications)

1.    Backes, W.L., Sligar, S.G. and Schenkman, J.B. (1980) Cytochrome P-450 Reduction Exhibits Burst Kinetics.  Biochem. Biophys. Res. Commun. 97, 860-867.

2.    Backes, W.L. and Canady, W.J. (1981) Solvent Effect on the Spectral Characteristics of Cytochrome P-450 - Specific Interactions with Dual Substrates. J. Biol. Chem. 256, 7213-7227.

3.    Backes, W.L., Hogaboom, M.L. and Canady, W.J. (1982) Factors Controlling the Association of Substrates to Cytochrome P-450:  Size Dependence for Hydrocarbon Binding.  J. Biol. Chem. 257, 4063-4071.

4.    Backes, W.L., Sligar, S.G. and Schenkman, J.B. (1982) Burst Kinetics of Cytochrome P-450 Reduction and Correlation Between Reduction and Spin State.  Biochemistry 21, 1324-1330.

5.    Schenkman, J.B., Jansson, I., Backes, W.L., Cheng, K.-C. and Smith, C. (1982) Dissection of Cytochrome P-450 Isozymes (RLM) from Fractions of Untreated Rat Liver Microsomal Proteins.  Biochem. Biophys. Res. Commun. 107, 1517-1523.

6.    Backes, W.L., Means, M.L. and Canady, W.J. (1984) Competition Between Hydrocarbon and Barbiturate for Spectral Binding to Hepatic Cytochrome P-450:  Inferences Concerning Spin State of the Enzyme.  J. Biol. Chem. 259, 10092-10099.

7.    Backes, W.L., Tamburini, P.P., Jansson, I., Gibson, G.G., Sligar, S.G. and Schenkman, J.B. (1985) Kinetics of Cytochrome P-450 Reduction:  Evidence for Faster Reduction of the High-Spin Ferric State.  Biochemistry 24, 5130-5136.

8.    Backes, W.L., Jansson, I., Mole, J.E., Gibson, G.G. and Schenkman, J.B. (1985) Isolation and Comparison of Four Cytochrome P-450 Enzymes from Phenobarbital-Induced Rat Liver:  Three Forms Possessing Identical NH2-Terminal Sequences.  Pharmacology 31, 155-169.

9.    Backes, W.L. and Reker-Backes, C.E. (1988) The Effect of NADPH Concentration on the Reduction of Cytochrome P-450 LM2.  J. Biol. Chem. 263, 247-253.

10.  Backes, W.L., Turner, J., Heimann, T.G. and Canady, W.J. (1986) Association of Hydrophobic Substances with Hemin - Characteristics of the Reverse Type I Binding Spectrum and its Relationship to Cytochrome P-450.  Biochemical Pharmacology 35, 4443-4448.

11.  Tamburini, P.P., Jansson, I., Favreau, L.V., Backes, W.L. and Schenkman, J.B. (1986) Differences in the Spectral Interactions Between NADPH-Cytochrome P-450 Reductase and a Series of Cytochrome P-450 Enzymes.  Biochem. Biophys. Res. Commun. 137, 437-442.

12.  Backes, W.L., and Eyer, C.S. (1989) Cytochrome P-450 LM2 Reduction:  Substrate Effects on the Rate of Reductase-LM2 Association.  J. Biol. Chem. 264, 6252-6259.

13.  Causey, K.M., Eyer, C.S. and Backes, W.L. (1990) Dual Role of Phospholipid in the Reconstitution of Cytochrome P-450 LM2-Dependent Activities.  Mol. Pharmacol. 38, 134-142.

14.  Eyer, C.S. and Backes, W.L. (1991) Relationship Between the Rate of Reductase - Cytochrome P450 Complex Formation and the Rate of First Electron Transfer.  Arch. Biochem. Biophys. 293, 231-240.

15.  Sequeira, D.J., Eyer, C.S. Cawley, G.F., Nick, T.G. and Backes, W.L. (1992) Ethylbenzene-mediated Induction of Cytochrome P450 Isozymes in Male and Female Rats. Biochem. Pharmacol. 44, 1171-1182.

16.  Backes, W.L., Sequeira, D.J., Cawley, G.F., and Eyer, C.S. (1993) Relationship Between Hydrocarbon Structure and Induction of Cytochrome P450: Effects on Protein Levels and Enzyme Activities. Xenobiotica 23, 1353-1366.

17.  Backes, W.L., Cawley, G., Eyer, C.S., Means, M., Causey, K.M. and Canady, W.J. (1993) Aromatic Hydrocarbon Binding to Cytochrome P450 and Other Enzyme Binding Sites: Are Hydrophobic Compounds Drawn into the Active Site or Pushed from the Aqueous Phase?  Arch. Biochem. Biophys. 304, 27-37.

18.  Sequeira, D.J., Cawley, G.F., Eyer, C.S., and Backes, W.L. (1994) Temporal Changes in P-450 2E1 Expression with Continued Ethylbenzene Exposure.   Biochim. Biophys. Acta 1207, 179-186. 

19.  Yuan, W., Cawley, G.F., Eyer, C.S., and Backes, W.L. (1994)  Induction of P450 3A by Ethylbenzene Without Altering RNA Levels.  Biochem. Biophys. Res. Commun. 202, 1259-1265.

20.  Yuan, W., White, T.B., Yuan, W., White, J.W., Strobel, H.W., and Backes, W.L. (1995) Relationship Between Hydrocarbon Structure and Induction of Cytochrome P450: Effect on RNA Levels. Xenobiotica 25, 9-16.

21.  Cawley, G.F., Batie, C.J., and Backes, W.L. (1995) Substrate-Dependent Competition of Different P450 Isozymes for Limiting NADPH-Cytochrome P450 Reductase.  Biochemistry 34, 1244-1247.

22.  Yuan, W., Serron, S.C., Cawley, G.F., Eyer, C.S., and Backes, W.L. (1997)  Ethylbenzene Modulates the Expression of Different Cytochrome P450 Isozymes by Unique Multistep Processes.  Biochim. Biophys. Acta 1334, 361-372.

23.  Yuan, W., Sequeira, D.J., Cawley, G.F., Eyer, C.S., and Backes, W.L. (1997) Time Course for the Modulation of Cytochrome P450 After Administration of Ethylbenzene and its Correlation with Toluene Metabolism.  Arch. Biochem. Biophys.  339, 55-63.

24.  Bergeron1, R.M., Serron, S.C., Rinehart, J.J., Cawley, G.F., and Backes, W.L.  (1998)  Pituitary Component of the Ethylbenzene-Mediated Expression of Cytochrome P450s 2B1, 2B2 and 2C11.  Xenobiotica 28, 303-312.

25.  Backes, W.L., Batie, C.J., and Cawley, G.F. (1998) Interactions Among P450 Isozymes: Evidence for the Existence of a 2B4-1A2-Reductase Complex with Altered Catalytic Function.  Biochemistry  37, 12852-12859.

26.  Bergeron, R.M., Desai, K., Serron, S.C., Cawley, G.F., Eyer, C.S. and Backes, W.L., (1999) Changes in the Expression of Cytochrome P450s 2B1, 2B2, 2E1, and 2C11 in Response to Daily Aromatic Hydrocarbon Treatment.  Toxicol. Applied Pharmacol.  157, 1-8.

27.  Serron, S.C., Dwivedi, N., and Backes, W.L. (2000) Ethylbenzene Induces Microsomal Oxygen Free Radical Generation: Antibody-directed characterization of the responsible cytochrome P450 isozymes. Toxicol. Applied Pharmacol. 164, 305-311.

28.  Serron, S.C., Zhang, S., Bergeron, R.M., and Backes, W.L., (2001) Effect of Hypophysectomy and Growth Hormone Replacement on the Modulation of P450 Expression after Treatment with the Aromatic Hydrocarbon Ethylbenzene Toxicol. Applied Pharmacol. 172, 163-171.

29.  Backes, W.L., Zhang, S., and Cawley, G.F., (2001) Evidence supporting the interaction of P450 2B4 and 1A2 in microsomal preparations Drug Metabol. Dispos. 29, 1529-1534. 

30.  Backes, W.L. and Serron, S.C., (2001) Invited response to a letter to the editor regarding “Ethylbenzene Induces Microsomal Oxygen Free Radical Generation: Antibody-directed characterization of the responsible cytochrome P450 isozymes”. Toxicol. Applied Pharmacol. 173, 189-189.

31.  Zhang, S., Cawley, G.F., Eyer, C.S., and Backes, W.L. (2002) Altered Ethylbenzene-Mediated Hepatic CYP2E1 Expression in Growth Hormone Deficient Dwarf Rats. Toxicol. Applied Pharmacol. 179, 74-82.

32.  Hunt, J.D., Strimas, A., Martin, J.E., Eyer, M., Haddican, M., Luckett, B.G., Ruiz, B., Axelrad, T. W., Backes, W.L., and Fontham, E.T.H. (2002) Differences in KRAS Mutation Spectrum in Lung Cancer Cases between African Americans and Caucasians after Occupational or Environmental Exposure to Known Carcinogens.  Canc. Epidem. Biomarkers Prev. 11, 1405-1412.

33.  Backes, W.L. and Kelley, R.W. (2003) Organization of Multiple Cytochrome P450s and NADPH-cytochrome P450 Reductase in Lipid Membranes, Pharmacol. Ther., 98, 221-233.

34.  Cheng, Dongmei, Kelley, R.W., Cawley, G.F., and Backes, W.L.  (2004) High Level Expression of Recombinant Rabbit Cytochrome P450 2E1 in Escherichia coli C41 and Its Purification.  Prot. Express. Purific. 33, 66-71.

35.  Kelley, R.W., Reed, J.R. and Backes, W.L. (2005) Effects of Ionic Strength on the Functional Interactions between CYP2B4 and CYP1A2.  Biochemistry, 44, 2632-2641.

36.  Backes, W.L., Kelley, R.W., Cheng, D., and Reed, J.R. (2005) How are NADPH-cytochrome P450 Reductase and Multiple Cytochromes P450 Organized in Membranes?  Proceedings from the 14th International Conference on Cytochrome P450: Biochemistry, Biophysics and Bioinformatics 163-170.

37.  Reed, J.R., Kelley, R.W., and Backes, W.L. (2006) An Evaluation of Methods for the Reconstitution of Cytochromes P450 and NADPH P450 Reductase into Lipid Vesicles.  Drug Metab. Dispos. 34, 660-666.

38.  Cormier, S.A., Lomnicki, S., Backes, W., and Dellinger, B. (2006) Origin and Health Impacts of Emissions of Toxic By-Products and Fine Particles from Combustion and Thermal Treatment of Hazardous Wastes and Materials. Environmental Health Persp. 114, 1-10.

39.  Kelley, R.W., Cheng, D., and Backes, W.L. (2006) Heteromeric Complex Formation Between CYP2E1 and CYP1A2: Evidence for the Involvement of Electrostatic Interactions. Biochemistry 45, 15807-15816.

40.  Cheng, D., Reed, J.R. Harris, D., and Backes, W.L. (2007) Inhibition of CYP2B4 by the Mechanism-based inhibitor 2-Ethynylnaphthalene: Inhibitory Potential of 2EN is Dependent on Substrate Size. Arch. Biochem. Biophys. 462, 28-37.

41.  Cheng, D., Harris, D., Reed, J.R. and Backes, W.L. (2007) Inhibition of CYP2B4 by the Mechanism-based inhibitor 2-Ethynylnaphthalene: Evidence for the Co-Binding of Substrate and Inhibitor within the Active Site. Arch. Biochem. Biophys. 468, 174-182.

42.  Huber, W.J. and Backes, W.L. (2007) Expression and Characterization of Full-Length Human Heme Oxygenase-1: Presence of intact membrane-binding region leads to increased binding affinity for NADPH-cytochrome P450 reductase. Biochemistry 46(43); 12212-12219.

43.  Huber, W.J. and Backes, W.L. (2008) Quantitation of Heme Oxygenase-1: Heme Titration Increases Yield of Purified Protein, Anal. Biochem. 373, 167-169.

44.  Reed, J.R., Brignac-Huber, L.M., Backes, W.L. (2008) Physical Incorporation of NADPH-cytochrome P450 Reductase and Cytochrome P450 into Phospholipid Vesicles using Glycocholate and Biobeads. Drug Metab. Dispos. 36, 582–588.

 

C. Research Support. List selected ongoing or completed (during the last three years) research projects (federal and non-federal support). Begin with the projects that are most relevant to the research proposed in this application. Briefly indicate the overall goals of the projects and responsibilities of principal investigator identified above.

 

Project Number – R01 ES004344:  Backes (PI)       8/1/02 – 4/30/08                      35 % effort

Funding Agency – NIEHS                              active

Title:  "Toxicological Significance of Alkylbenzene Metabolism"

The toxicity and carcinogenicity of simple aromatic hydrocarbons is known to be due to its bioactivation to reactive intermediates.  This process requires a functional interaction between P450 and P450 reductase.  The proposed studies are designed to address questions related to the organization of P450 and reductase.  We identified important interactions among CYP2B4, CYP1A2 and reductase that affect substrate metabolism.  We propose to characterize these interactions, and to identify the region(s) responsible for this effect.  We also will examine the role of these interactions on the bioactivation of hydrocarbons and ROS generation by P450. 

 

Project Number – NIH-T32 AA07577; Backes (member of core faculty)          9-1-2004 – 8-31-2009       active

Title –Biomedical alcohol Research Training Program, (Bagby/Shellito – Principal Investigators).

 

Project Number – R01 ES004344:  Backes (PI)       2/1/09 – 1/31/14                      35 % effort

Funding Agency – NIEHS                              pending

Title:  "Toxicological Significance of Alkylbenzene Metabolism"

The toxicity and carcinogenicity of simple aromatic hydrocarbons is known to be due to its bioactivation to reactive intermediates.  This process requires a functional interaction between P450 and P450 reductase.  The proposed studies are designed to extend our investigation and address questions related to the organization of reductase and P450, their interactions within the endoplasmic reticulum, and how these interactions affect xenobiotic metabolism, including the metabolism of alkylbenzenes.  We plan to continue our characterization of these interactions, examining (1) the functional consequences of P450-P450 interactions, (2) the structural basis for these interactions by identifying the region(s) responsible for P450-P450 complex formation, and (3) the organizational consequences to P450-P450 complex formation (i.e. how do such interactions affect their regional distribution in the endoplasmic reticulum).  These studies will increase our understanding of how the P450 electron transport chain is organized, and will provide new important information on the role of the P450 system in the bioactivation of aromatic hydrocarbons and the generation of reactive oxygen – a process that can have a significant influence on chemical toxicity.

 

Project Number – P42 ES013648-01A2 Superfund Dellinger (PI), Backes (co-PI for program)   

Administrative core – 10% effort              Project 4 – Backes (PI) 15% effort

Funding Agency – NIEHS and EPA         pending

4/1/08 – 3/31/13                     

Title - Health Impacts of Toxic Combustion By-Products

The goal of this study is to examine the health risks associated with exposure to ultrafine particulates.  The study will focus on the effects on bioactivation of the hydrocarbon constituents by the P450 system.