Philip Lazarus
Chair, Pharmaceutical SciencesBoeing Distinguished Professor 509-358-7947 PBS 431 Spokane

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. Lazarus’ research focuses on examining the metabolism of drugs and tobacco constituents including major tobacco carcinogens, and how individual genetic variants play a role in cancer risk and drug toxicity and effectiveness. His laboratory was one of the first to study gene-environment interactions and their role in head and neck as well as lung cancer risk. His studies on nicotine metabolism and differences in nicotine addiction has led to more recent studies developing novel smoking cessation agents.  In addition, his laboratory has studied the pharmacogenetics of breast cancer agents including serum estrogen receptor modulators and anti-aromatase inhibitors, and has undertaken new studies investigating the potential role of marijuana constituents in drug-drug interactions with opioids and drug addiction and toxicity. Dr. Lazarus is a leader in studies of the UGT phase II family of enzymes and has numerous papers studying their regulation and their role in cancer risk and drug addiction.

Dr. Lazarus has been continuously funded by the National Institutes of Health (USA) since 1995 and has received >$18.5 million from NIH to date. He has published over 195 peer-reviewed papers, has served both ad hoc and as a full member on several NIH study sections, serves on the editorial board of Molecular Pharmacology, and has chaired and presented at numerous national and international meetings.

Selected publications

(chosen from over 200 publications since 2015)

Modesto JL, Hull A, Angstadt A, Berg A, Gallagher CJ, Lazarus P, Muscat JE. NNK reduction pathway gene polymorphisms and risk of lung cancer. Mol Carcinogen. 2015; 54:E94–E102 PMID: 24976539

Gufford BT, Chen G, Lazarus P, Oberlies NH, Paine MF. Milk Thistle Constituents Inhibit Raloxifene IntestinalGlucuronidation: a Potential Clinically Relevant Natural Product-Drug Interaction. Drug Metabol Dispos. 2015; 43(9):1353-9. PMID: 26070840

Chen L-S, Hung R, Baker T, Horton A, Culverhouse R, Saccone N, Cheng I, Deng B, Han Y, Hansen H, Horsman J, Kim C, Lutz S, Rosenberger A, Aben K, Andrew A, Naomi B, Chang S-C, Dieffenbach A, Dienemann H, Frederiksen B, Han J, Hatsukami D, Johnson E, Pande M, Wrensch M, McLaughlin J, Skaug V, van der Heijden E, Wampfler J, Wenzlaff A, Woll P, Zienolddiny S, Bickeböller H, Brenner H, Duell E, Haugen A, Heinrich J, Hokanson J, Hunter D, Kiemeney L, Lazarus P, Le Marchand L, Liu G, Mayordomo J, Risch A, Schwartz A, Teare MD, Wu X, Wiencke J, Yang P, Zhang Z-F, Spitz M, Kraft P, Amos C, and Bierut L. CHRNA5 Risk Variant Predicts Delayed Smoking Cessation and Earlier Lung Cancer Diagnosis – A Meta-analysis. J Natl Cancer Inst. 2015; May 107(5). PMID: 25873736
*Chosen by NCI’s Epidemiology and Genomics Research Program as a Research Highlight for 2015

McGrath-Morrow SA, Hayashi M, Aherrera A, Lopez A, Malinina A, Collaco JM, Neptune E, Klein JD, Winickoff JP, Breysse P, Lazarus P, Chen G. The effects of E-cigarette exposure on systemic cotinine levels and postnatal lung growth in neonatal mice. PlosOne. 2015; Feb 23;10(2):e0118344. PMID: 25706869

Ashmore J, Gallagher CJ, Lesko SM, Muscat JE, Hartman T, Lazarus P. No association between vitamin D intake, VDR polymorphisms, and colorectal cancer in a population-based case-control study. Cancer Epidemiol Biomarkers Prev. 2015; 24(10):1–3. PMID: 26224799

Kozlovich S, Chen G, Lazarus P. Stereospecific metabolism of the tobacco specific nitrosamine, NNAL. Chem Res Toxicol. 2015; 28(11):2112-9. PMID: 26452127

Jones N, Ashmore J, Lee S, Richie J Jr., Lazarus P, Muscat J. Association studies of HFE C282Y and H63D variants with oral cancer risk and iron homeostasis in Whites and Blacks. Cancer. 2015; 7(4):2386-96. PMID: 26690219

Smith D, Aherrera A, Lopez A, Neptune E, Winickoff J, Klein J, Lazarus P, Chen G, Collaco JM, McGrath-Morrow SA. Adult behavior in male mice exposed to E-cigarette nicotine vapors during late prenatal and early postnatal life. PlosOne. 2015; Sept 15; 10(9):e013795 PMID: 26372012

Dluzen DF and Lazarus P. MicroRNA regulation of the major drug-metabolizing enzymes and related transcription factors. Drug Metab Rev. 2015; 24:1-15 PMID: 26300547

White JR, Jr, Padowski JM, Zhong Y, Chen G, Luo C, Lazarus P, Layton ME, McPherson S. Pharmacokinetic Analysis and Comparison of Caffeine Administered Rapidly or Slowly in Coffee Chilled or Hot vs. Chilled Energy Drink in Healthy Young Adults. Clin Toxicol (Phila). 2016; 54(4):308-12. PMID: 27100333

Platt A, Xia Z, Liu Y, Chen G, and Lazarus P. Impact of nonsynonymous single nucleotide polymorphisms on in-vitro metabolism of exemestane by hepatic cytosolic reductases. Pharmacogen Genomics. 2016; 26(8):370-80. PMID: 27111237

Chen G, Luo S, Kozlovich S, Lazarus P. Association between Glucuronidation Genotypes and Urinary NNAL Metabolic Phenotypes in Smokers. Cancer Epidemiol Biomarkers Prev. 2016; 25(7):1175-84. PMID: 27197298

Dluzen DF, Sutliff AK, Chen G, Watscon CJ, Ishmail FT, Lazarus P. Regulation of UGT2B expression and activity by miR-216b in liver cancer cell lines. J Pharmacol Exper Ther. 2016; 359:182-193. PMID: 27474751

Remsberg CM, Bray BS, Wright SK, Ashmore J, Kabasenche W, Wang S, Lazarus P, Daoud SS. Instructional design and assessment. Design, implementation, and assessment approaches within a pharmacogenomics course. Amer J Pharmaceut Educ. 2017; 81(1):11. PMID: 28289301

Peterson A, Xia Z, Chen G, Lazarus P. In vitro metabolism of exemestane by hepatic cytochrome P450s: impact of nonsynonymous polymorphisms on formation of the active metabolite 17β-dihydroexemestane. Pharmacol Res Perspect. 2017; Apr 27;5(3):e00314. PMID: 28603633

Peterson A, Xia Z, Chen G, Lazarus P. Exemestane Potency is unchanged by common nonsynonymous polymorphisms in CYP19A1: Results of a novel anti-aromatase activity assay examining exemestane and its derivatives. Pharmacol Res Perspect. 2017; 5(3):e00313. PMID: 28603632

Laube BL, Afshar-Mohajer N, Koehler K, Chen G, Lazarus P, Collaco JM, McGrath-Morrow SA. Acute and Chronic in Vivo Effects of Exposure to Nicotine and Propylene Glycol from an E-cigarette on Mucociliary Clearance in a Murine Model. Inhal Toxicol. 2017; Apr, 29(5):197-205. PMID: 28651446

Huang J, Liu Y, Vitale S, Penning TM, Whitehead AS, Blair IA, Vachani A, Clapper ML, Muscat JE, Lazarus P, Scheet P, Moore JH, Chen Y. On meta- and mega-analyses for gene-environment interactions Genetic Epidemiol. 2017; Nov, 41(8):876-886. PMID: 29110346.

Luo S, Chen G, Truica C, Baird CC, Leitzel K, Lazarus P. Role of the UGT2B17 deletion in exemestane pharmacogenetics. Pharmacogen J. 2018; Apr, 18(2):295-300. PMID: 28534527.

Denton TT, Srivastava P, Xia Z, Chen G, Watson C, Wynd A, Lazarus P. Identification of the 4-position of 3-alkynyl and 3-heteroaromatic substituted pyridine methanamines as a key modification site eliciting increased potency and enhanced selectivity for cytochrome P-450 2A6 inhibition. J Med Chem. 2018; Aug 23, 61(16):7065-7086. PMID: 29995408.

Luo S, Chen G, Truica CI, Baird CC, Xia Z, Lazarus P. Identification and Quantification of Novel Major Metabolites of the Steroidal Aromatase Inhibitor, Exemestane. Drug Metab Dispos. 2018; Dec, 46(12):1867-1878. PMID: 30257855.

Perez-Paramo YX, Chen G, Ashmore JH, Watson CJW, Nasrin S, Adams-Haduch J, Wang R, Gao Y-T, Koh W-P, Yuan J-M, Lazarus P. Nicotine-N’-oxidation by flavin monooxygenase enzymes. Cancer Epidmiol Biomarkers Prev. 2019 Feb, 28(2):311-320. PMID: 30381441.
*Chosen as ‘Authors Choice’ for this issue of Cancer Epidmiol Biomarkers Prev.

Dai J, Li Z, Amos CI, Hung RJ, Tardon A, Andrew A, Chen C, Christiani DC, Albanes D, van der Heijden EHFM, Duell E, Rennert G, Mckay JD, Yuan J-M, Field JK, Manjer J, Grankvist K, Marchand LL, Teare MD, Schabath MB, Aldrich MC, Tsao M-S, Lazarus P, Lam S, Bojesen SE, Arnold S, Wu X, Hu Z, Shen H. Systematic analyses of regulatory variants in DNase I hypersensitive regions identified in two novel lung cancer susceptibility loci. Carcinogenesis. 2019; May 14, 40(3):432-440. PMID: 30590402.

Sutliff AK, Watson CJW, Chen G, Lazarus P. Regulation of UGT2A1 by miR-196a-5p and miR-196b-5p. J Pharmacol Exper Ther. 2019; May, 369(2):234-243. PMID: 30850392.

Liu SN, Lu JBL, Watson CJW, Lazarus P, DestaZ, Gufford BT. Mechanistic Assessment of Extrahepatic Contributions to Glucuronidation of Integrase Strand Transfer Inhibitors. Drug Metab Dispos. Feb 25, 2019; May, 47(5):535-544. PMID: 30804050.

Ashmore JH, Luo S, Watson C, and Lazarus P. Carbonyl reduction of NNK by recombinant human lung enzymes. Identification of HSD17β12 as the reductase important in (R)-NNAL formation in human lung. Carcinogenesis. 2018; May 17, doi: 10.1093/carcin/bgy065. [Epub ahead of print]. PMID: 29788210.

Sutliff AK, Shi J, Chen G, Watson CJW, Zhu H, Lazarus P. Regulation of UGT2B10 and UGT2B7 by miR-485-5p in human liver. Mol Pharmacol. (submitted, under revision)

Kozlovich S, Chen G, Watson CJW, Lazarus P. Prominent Stereoselectivity of NNAL Glucuronidation in Head and Neck Tissues. Carcinogenesis. (submitted)

Kozlovich S, Chen G, Watson CJW, Blot WJ, Lazarus P. The role of L- and D-menthol in the glucuronidation and detoxification of the major lung carcinogen, NNK. Carcinogenesis. (submitted)

More Publications

Grants

Active

1R01 ES025460-01A1 (Lazarus, P)                                                              2015-2020
NIH/NIEHS
“The UGT2A and 3A metabolizing enzymes and tobacco-related cancer risk”
The goal of this proposal is to examine the role of two previously under-studied phase II metabolizing enzyme sub-families (UGT2A and UGT3A) on drug response and cancer risk.

Faculty Pilot Grant on Drug & Alcohol Abuse, WSU     (Lazarus, P)             2019-2020
The overlapping metabolism of opioids and cannabis: Potential consequences for toxicity and withdrawal among opioids users.
The goal of this study is to examine the metabolic pathways involved in the metabolism of major cannabis constituents and their metabolites, and to explore potential drug-drug interactions between cannabis compounds and major opioids including hydrocodone and morphine.

Completed (selected)

1 RO1 CA59917 (Lazarus, P; re-funded once)                                             1995–2008
NIH/NCI
Title: Analysis of 5’ UTR-mediated regulation of p53 expression.
The major goal of this project will be to better understand the mechanisms underlying this novel regulatory pathway for the p53 tumor suppressor protein and to elucidate whether this regulation can serve as a biomarker cancer development and progression.

1 RO1 DE12206         (Lazarus, P)                                                                1997-2002
NIH/NCI
Title: Molecular markers of oral cancer risk.
The major goal of this project was to elucidate highly susceptible genotypic and phenotypic profiles for xenobiotic-metabolizing enzymes as determinants of oral cancer risk for different racial groups.

PO1-CA68384 (Lazarus, P; re-funded once)                                                2001-2008
NIH/NCI
Title: Tobacco and cancer risk: Dose, metabolism and genetics
The major goal of this program project is the examination of epidemiologic and molecular factors involved in risk for tobacco-related cancers.  Dr. Lazarus is a project leader for one of the three independent projects within this proposal, and is co-investigator on a second project led by J.P. Richie.

R01 DE013158-13 (Lazarus, P; re-funded once)                                          2001-2013
NIH/NIDCR
“UDP-Glucuronosyltransferase Genotype and Cancer Risk”
The major goals of this application has been to examine the role of UGT family of enzymes in genetic susceptibility to cancer. This grant has been funded for 13 consecutive years and received a 13 percentile score from the Oct 2012 XNDA review panel.  Parent committee review for funding is expected in 2013.

National Functional Genomics Center (Lazarus, P)                                      2003-2004
H. Lee Moffitt Cancer Center/DOD
Title: In vitro modeling of tobacco-induced cellular regulatory pathways.
The goal of this pilot project was to identify genes important in tobacco carcinogen-induced tumorigenesis using a cell line model.

Tobacco Block Grant, Penn State University (Lazarus, P)                            2003-2006
Title: Tobacco – genetic interactions and cancer induction.
The major goal of this project was to examine the role of common genetic varia-tions in metabolism and DNA repair pathways on enzyme activities both in vivo & in vitro.

PA State Contractual Agreement (Lazarus, P)                                              2004-2005
Title: Feasibility study of population-based research in Appalachia, PA.
The goal of this study was to establish the feasibility of performing subject recruitment in rural Appalachia for research and outreach.

PA Tobacco Settlement Funds (Pegg, T; Lazarus, P, Proj Leader)              2004-2006
Title: Role of antizyme and polyamines in tumor development. Project 2 title: Identification of AZ-1 and ODC polymorphisms and their potential importance in cancer risk.
The major goal of this project was to identify polymorphisms in the genes coding for antizyme and ornithine decarboxylase and examine the potential role of these variations in cancer risk.

PA Tobacco Settlement Funds (Lazarus, P)                                                 2005-2007
Title: UDP glucuronosyltransferase: Role in cancer susceptibility and treatment.
This program project was focused on the role of the UDP glucuronosyltransferase (UGT) superfamily of enzymes in cancer treatment.

PA Tobacco Settlement Fund (Lazarus, P)                                                   2005–2008
Title: UDP glucuronosyltransferase: Role in cancer susceptibility and treatment.
This program project is focused on the role of the UDP glucuronosyltransferase (UGT) superfamily of enzymes in cancer treatment.

Dean’s Feasibility Grant (Lazarus, P)                                                             2007-2009
Penn State University College of Medicine
Title: Role of UGTs in tamoxifen pharmacogenetics
The goal of this proposal is to better examine the role of the UGT family of enzymes and their genetics in patient response to tamoxifen.

SAP #4100038714, Yr. 4 (Lazarus, P)                                                          2007-2011
PA Department of Health/Univ. of Penn. (Whitehead)
“Center for the Study of Gene-Environment Interactions in Lung Cancer”
The goal of this proposal is to examine the interaction between variants in metabolic genes and environmental exposures and risk for lung cancer.

SAP# 410003815 (Lazarus, P)                                                                      2007-2011
PA Department of Health
“Gene-Environment Interactions for Colorectal Cancer in Northeast, PA”
The goal of this proposal is to examine the interaction between variants in genes involved in heterocyclic amine, nitrosamine and polycyclic aromatic hydrocarbon metabolism and environmental exposures like smoking and diet.

K099 (Gallagher, C; Lazarus, P – mentor)                                                     2008-2010
NIH/NCI
Title: Role of gender in risk for tobacco-related cancers
Dr. Lazarus served as the primary mentor for Dr. Gallagher during the 2-year mentorship phase of this proposal.

7-08-CST-01, (Lazarus, P)                                                                             2008-2011
American Diabetes Association
Title: The Effects of UDP-Glucuronosyltansferase Polymorphisms on Olanzapine Metabolism:  Implications for Obesity and Diabetes Risk.
This was a fellowship award awarded to my graduate student, Kathryn Erickson.

Clinical & Translational Research Award (Cream, L; Lazarus, P; Co-PIs)   2009-2010
Penn State University College of Medicine                                                   
Title: Role of UGTs in tamoxifen pharmacogenetics            
The goal of this proposal is to better examine the role of the UGT family of enzymes and their genetics in patient response to tamoxifen.

3R01 GM077482-07S1 (Paine, M)                                                                2013-2015
NIH/NIGMS
‘Mechanisms Underlying Drug-Diet Interactions’
The goal of this study is to advance the mechanistic understanding of potential clinically significant interactions between conventional medications and dietary substances.  Specifically, the role of flavonolignans present in milk thistle in drug-drug interactions will be explored.
Role: Co-Investigator

1R01 ES025460-01Suppl (Lazarus, P)                                                         2016-2018
NIH/NIEHS
“The UGT2A and 3A metabolizing enzymes and tobacco-related cancer risk”
This is a supplemental award to Ana Vergara, a graduate student in the lab of Dr Lazarus.

1R01 CA164366-01A1 (Lazarus, P)                                                              2012-2018
NIH/NCI
“Role of Pharmacogenetics on Exemestane Metabolism and Toxicity”
This is a collaborative study with Queens Unversity (Kingston, ON), Penn State University (Hershey, PA) and Harvard University (Boston, MA) to fully characterize the metabolism of the aromatase inhibitor, exemestane (commonly used for the treatment and prevention of breast cancer), and to explore the effects, both in vitro and in vivo, of polymorphisms that occur in enzymes that mediate exemestane metabolic reactions.

Student Grants

Y Perez-Paramo: Fellowship for Doctorate Studies, Mexico                   2018-2020
Comisión Nacional de Ciencia y Tecnología (CONACyT) ($30,000/y)

Y Perez-Paramo: Fulbright García-Robles Fellowship                              2015 – 2018
Fulbright Program, US-Mexico ($30,000/y)

D Dluzen: Pfizer Fellowship ($30,000 USD/year)                                      2010-2011

updated 05/28/2019