Philip Lazarus, Ph.D.

Education
Ph.D., McGill University, Montreal, Quebec, Canada; Experimental Medicine

Bachelor of Science, McGill University, Montreal, Quebec, Canada; Human Genetics

Fellowships & Additional Training
Postdoctoral Fellowship, McGill University, Montreal, Quebec, Canada; Biochemistry

Research
Dr. Philip Lazarus’ research is focused on the elucidation of carcinogenic mechanisms with an underlying theme of cancer prevention, focusing primarily on mechanisms involved in the induction and progression of tobacco-related cancers. As the major risk factor for aerodigestive tract cancer induction is the use of tobacco products, a major focus has been the study of tobacco carcinogen metabolism and the identification of biochemical and molecular markers of tobacco-induced carcinogenesis.

On-going studies include the following:
A. Molecular epidemiologic studies examining genetic and phenotypic polymorphisms in xenobiotic-metabolizing enzyme as well as DNA repair genes as markers for cancer risk. The carcinogenic activity of tobacco carcinogens can often depend on the cellular composition/expression/activity of enzymes that are involved in the activation or detoxification of many tobacco carcinogens or the repair of the DNA adducts they induce. The expression and/or activity of these enzymes may be a critical determinant of individual risk for tobacco carcinogen-induced damage. Studies from Lazarus' laboratory have identified function/expression-altering genetic polymorphisms for a number of these enzymes, and have shown that they may play a role in increased risk for certain cancers. Current studies are focused upon the identification of high-risk genotypes important in risk for other cancers including colon, esophageal and breast cancer, identification of novel chemoprevention agents, and enzyme promoter characterization and induction mechanisms.

B. Studies characterizing carcinogen metabolic pathways and examining their role in cancer susceptibility. Studies have focused on enzyme pathways involved in the detoxification of the potent carcinogens benzo(a)pyrene and NNK.

C. Studies are on-going examining a novel mechanism of regulation of the p53 tumor suppressor protein. Recent studies from Dr. Lazarus' lab have demonstrated that a novel transcription-coupled translational control mechanism appears to play a role in regulating p53 protein synthesis in normal versus tumor tissues. These studies suggest that this novel translational control mechanism may play an important role in the up-regulation of p53 protein expression observed upon cellular insult or tumor initiation. Current studies have focused upon the characterization of this novel regulatory mechanism.

Recent Presentations
"Potential Effects on Drug–Drug Interactions and Disease Susceptibility by Regulation of UGT Activity/Expression via Epigenetic Mechanisms (miRNA) and Alternate Splicing" presented at the Translation of Preclinical Drug–Drug Interaction and Metabolism Data into Risk Assessment of Clinical Toxicity symposium at the New York Academy of Sciences Conference Center in New York City. October 21, 2013

Publications since 2011
Angstadt AY, Zhu J, Muscat JE, Hartman TJ, Lesko SM, Gallagher CJ, Lazarus P. The effect of UGT1A and UGT2B polymorphisms on colorectal cancer risk: haplotype associations and gene-environment interactions. Genes Chrom Cancer. In press.

Jones NR, Lazarus P. UGT2B gene expression analysis and identification of stably-expressed control genes for use in real-time PCR in multiple organ sites. Drug Metabol Dispos. In press.

Dluzen DF, Sun D, Salzberg AC, Jones N, Bushey RT, Robertson GP, Lazarus P. Regulation of UGT1A1 expression and activity by miR-491-3p. J Pharmacol Exper Ther. In press.

Marks MA, Chaturvedi AK, Kelsey K, Straif K, Berthiller J, Schwartz SM, Smith E, Wyss A, Brennan P, Olshan AF, Wei Q, Sturgis EM, Zhang ZF, Morgenstern H, Muscat J, Lazarus P, McClean M, Chen C, Vaughan TL, Wunsch-Filho V, Curado MP, Koifman S, Matos E, Menezes A, Daudt AW, Fernandez L, Posner M, Boffetta P, Lee YC, Hashibe M, D'Souza G. Cancer Epidemiol Biomarkers Prev. 2013 Dec 18. [Epub ahead of print] PMID: 24351902

Baldwin DA, Sarnowski CP, Reddy SA, Blair IA, Clapper M, Lazarus P, Li M, Muscat JE, Penning TM, Vachani A, Whitehead AS. Development of a genotyping microarray for studying the role of gene-environment interactions in risk for lung cancer. J Biomol Tech. 2013 Dec;24(4):198-217. doi: 10.7171/jbt.13-2404-004. PMID: 24294113

Leoncini E, Ricciardi W, Cadoni G, Arzani D, Petrelli L, Paludetti G, Brennan P, Luce D, Stucker I, Matsuo K, Talamini R, La Vecchia C, Olshan AF, Winn DM, Herrero R, Franceschi S, Castellsague X, Muscat J, Morgenstern H, Zhang ZF, Levi F, Dal Maso L, Kelsey K, McClean M, Vaughan TL, Lazarus P, Purdue MP, Hayes RB, Chen C, Schwartz SM, Shangina O, Koifman S, Ahrens W, Matos E, Lagiou P, Lissowska J, Szeszenia-Dabrowska N, Fernandez L, Menezes A, Agudo A, Daudt AW, Richiardi L, Kjaerheim K, Mates D, Betka J, Yu GP, Schantz S, Simonato L, Brenner H, Conway DI, Macfarlane TV, Thomson P, Fabianova E, Znaor A, Rudnai P, Healy C, Boffetta P, Chuang SC, Lee YC, Hashibe M, Boccia S. Adult height and head and neck cancer: a pooled analysis within the INHANCE Consortium. Eur J Epidemiol. 2013 Nov 24. [Epub ahead of print] PMID: 24271556

Ashmore JH, Lesko SM, Muscat JE, Gallagher CJ, Berg AS, Miller PE, Hartman TJ, Lazarus P. Association of Dietary and Supplemental Folate Intake and Polymorphisms in Three FOCM Pathway Genes with Colorectal Cancer in a Population-Based Case-Control Study. Genes Chrom Cancer 2013; 52(10):945-53. PMID: 23893618

Ashmore JH, Lesko SM, Miller PE, Cross AJ, Muscat JE, Zhu J, Liao J, Harper G, Lazarus P, Hartman TJ. 2013. Association of dietary and supplemental iron and colorectal cancer in a population-based study. Eur J Cancer Prev. 2013; Mar 12. [Epub ahead of print].

Wyss A and 45 others including Lazarus P. Cigarette, cigar, and pipe smoking and the risk of head and neck cancer: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Amer J Epidemiol. 2013; 178(5):679-90. PMID: 23817919

Angstadt AY, Berg AS, Zhu J, Hartman TJ, Lesko SM, Muscat JE, Lazarus P, Gallagher CJ. The effect of copy number variation (CNV) in the phase II detoxification genes, UGT2B17 and UGT2B28, on colorectal cancer risk. Cancer. 2013; 119(13):2477-85. PMID: 23575887

Angstadt AY, Berg AS, Zhu J, Hartman TJ, Lesko SM, Muscat JE, Lazarus P, Gallagher CJ. The effect of copy number variation (CNV) in the phase II detoxification genes, UGT2B17 and UGT2B28, on colorectal cancer risk. Cancer. 2013; 119(13):2477-85. PMID: 23575887

Miller PE, Lazarus P, Lesko SM, Cross AJ, Sinha R, Laio J, Zhu J, Harper G, Muscat JE, Hartman TJ. Meat-Related Compounds and Colorectal Cancer Risk by Anatomical Subsite. Nutr Cancer. 2013; 65(2):202-26. PMID: 23441608

Bushey RT, Dluzen DF, Lazarus P. Importance of UDP-glucuronosyltransferases 2A2 and 2A3 in tobacco carcinogen metabolism. Drug Metab Dispos. 2013; 41(1):170-9. PMID: 23086198

Nichenametla SN, Muscat JE, Liao JG, Lazarus P, Richie JP Jr. A functional trinucleotide repeat polymorphism in the 5'-untranslated region of the glutathione biosynthetic gene GCLC is associated with increased risk for lung and aerodigestive tract cancers. Mol Carcinogen. 2013; 52(10):791-9. PMID: 22610501

Ma J, Xiao F, Xiong M, Andrew AS, Brenner H, Duell EJ, Haugen A, Hoggart C, Hung RJ, Lazarus P, Liu C, Matsuo K, Mayordomo JI, Schwartz AG, Staratschek-Jox A, Wichmann E, Yang P, and Amos CI. Natural and orthogonal interaction framework for modeling gene-environment interactions with application to lung cancer. Hum Hered. 2012; 73(4):185-94. PMID: 22889990

Bushey RT and Lazarus P. Identification and functional characterization of a novel UGT2A1 splice variant: Potential importance in tobacco-related cancer susceptibility. J Pharmacol Exper Ther. 2012; 343(3):712-24. PMID: 22984225

Brenner DR, and 41 others including Lazarus P. Previous Lung Diseases and Lung Cancer Risk: A Pooled Analysis from the International Lung Cancer Consortium. Amer J Epidemiol. 2012; 176(7):573-585. PMID: 22986146

Jones NR, Sun, D, Freeman WM, Lazarus P. Quantification of UGT1A v1 and v2/v3 splice variant expression in human liver tissue and correlation of UGT1A1 variant expression with glucuronidation activity. J Pharmacol Exper Ther. 2012; 342(3):720-729. PMID: 22661630

Li Q, and 31 others including Lazarus P. Vitamin or mineral supplement intake and the risk of head and neck cancer: pooled analysis in the INHANCE consortium. Int J Cancer. 2012; 131(7):1686-1699. PMID: 22173631.

Coté ML, and 59 others including Lazarus P. Increased risk of lung cancer in individuals with a family history of the disease: A pooled analysis from the International Lung Cancer Consortium. Eur J Cancer . 2012; 48(13):1957-1968. PMID:22436981

Erickson-Ridout KK, Sun D, Lazarus P. Glucuronidation of the second-generation antipsychotic clozapine and its active metabolite N-desmethylclozapine. Potential importance of UGT1A1 and UGT1A4 polymorphisms. Pharmacogen Genomics. 2012; 22(8):561-576. PMID: 22565219

Stott-Miller M, and 22 others including Lazarus P. History of diabetes and risk of head and neck cancer: a pooled analysis from the international head and neck cancer epidemiology consortium. Cancer Epidemiol Biomarkers Prev 2012; 21(2):294-304. PMCID: PMC3275674

Chuang SC, and 60 others including Lazarus P. Diet and the risk of head and neck cancer: a pooled analysis in the INHANCE consortium. Cancer Causes Control 2012; 23(1):69-88. PMID:22037906

Chen G, Giambrone NE, Lazarus P. Glucuronidation of trans-3'-hydroxycotinine by UGT2B17 and UGT2B10. Pharmacogenet Genomics 2012; 22(3):183-90. PMCID: PMC3275669

Olson KC, Sun D, Chen G, Sharma AK, Amin S, Ropson IJ, Spratt TE, Lazarus P. Characterization of dibenzo[a,l]pyrene-trans-11,12-diol (dibenzo[def,p]chrysene) glucuronidation by UDP-glucuronosyltransferases. Chem Res Toxicol 2011; 24(9):1549-59. PMCID: PMC3177992

Nichenametla SN, Lazarus P, Richie JP, Jr. A GAG trinucleotide-repeat polymorphism in the gene for glutathione biosynthetic enzyme, GCLC, affects gene expression through translation. FASEB J 2011; 25(7):2180-7. PMCID: PMC3114536

McKay JD, and 128 others including Lazarus P. A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium. PLoS Genet 2011; 7(3):e1001333. PMCID: PMC3060072

McCormack VA, and 18 others including Lazarus P. Aspirin and NSAID use and lung cancer risk: a pooled analysis in the International Lung Cancer Consortium (ILCCO). Cancer Causes Control 2011; 22(12):1709-20. PMID:21987079

Lubin JH, and 41 others including Lazarus P. An examination of male and female odds ratios by BMI, cigarette smoking, and alcohol consumption for cancers of the oral cavity, pharynx, and larynx in pooled data from 15 case-control studies. Cancer Causes Control 2011; 22(9):1217-31. PMCID: PMC3304584

Jones NR, Spratt TE, Berg AS, Muscat JE, Lazarus P, Gallagher CJ. Association studies of excision repair cross-complementation group 1 (ERCC1) haplotypes with lung and head and neck cancer risk in a Caucasian population. Cancer Epidemiol 2011; 35(2):175-81. PMCID: PMC3081042

Erickson-Ridout KK, Zhu J, Lazarus P. Olanzapine metabolism and the significance of UGT1A448V and UGT2B1067Y variants. Pharmacogenet Genomics 2011; 21(9):539-51. PMID:21750471

Crampsie MA, Jones N, Das A, Aliaga C, Desai D, Lazarus P, Amin S, Sharma AK. Phenylbutyl isoselenocyanate modulates phase I and II enzymes and inhibits 4-(methylnitrosamino)-1-(3-pyridyl)- 1-butanone-induced DNA adducts in mice. Cancer Prev Res (Phila) 2011; 4(11):1884-94. PMCID: PMC3208061

Chen D, and 67 others including Lazarus P. A sex-specific association between a 15q25 variant and upper aerodigestive tract cancers. Cancer Epidemiol Biomarkers Prev 2011; 20(4):658-64. PMCID: PMC3070066

Bushey RT, Chen G, Blevins-Primeau AS, Krzeminski J, Amin S, Lazarus P. Characterization of UDP-glucuronosyltransferase 2A1 (UGT2A1) variants and their potential role in tobacco carcinogenesis. Pharmacogenet Genomics 2011; 21(2):55-65. PMCID: PMC3019304

More Publications

updated 02/04/2014     Back to top
photo of Dr. Philip Lazarus

Chair and
Boeing Distinguished Professor

Pharmaceutical Sciences

phil.lazarus@wsu.edu
509-358-7947

Office: PBS 431
P.O. Box 1495
Washington State University
Spokane, WA  99210-1495