Craig Lee, Pharm.D., Ph.D.

Associate Professor

Craig Lee, Pharm.D., Ph.D., is an associate professor in the UNC Eshelman School of Pharmacy’s Division of Pharmacotherapy and Experimental Therapeutics. His mission is to optimize drug therapy through the generation, integration and translation of scientific information between the bench and the bedside, the patient and the population. He is also a member of the interdisciplinary UNC Center for Pharmacogenomics and Individualized Therapy, UNC McAllister Heart Institute and UNC Nutrition Obesity Research Center. Lee is a licensed pharmacist in North Carolina and is trained as a clinical/translational pharmaceutical scientist with expertise in cytochrome P450 metabolism and experimental therapeutics.

The overall objective of Lee’s research program is to improve understanding of the key mechanisms underlying interindividual variability in drug response as a means to develop novel therapeutic strategies that will improve public health. The focus of his research program is twofold.

  • First, he seeks to develop a thorough understanding of how cytochrome P450-derived eicosanoids (bioactive lipid mediators of arachidonic acid) regulate hepatic and extra-hepatic inflammatory responses, and determine whether modulation of this pathway will serve as an effective anti-inflammatory and end-organ protective therapeutic strategy for cardiovascular and metabolic disease. Using genomic and biomarker-guided strategies, he seeks to translate preclinical discoveries into humans and determine which subsets of the population may be most likely to respond to the therapeutic strategies under evaluation in our laboratory.
  • Second, he seeks to identify and elucidate the key factors that exacerbate inter-individual variability in the metabolism of and response to drugs currently on the market, and determine whether implementation of genomic and biomarker-guided strategies can reduce this variability in metabolism and response and ultimately improve outcomes.
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Over the past decade, Lee has established a highly collaborative and translational research program that integrates mechanistically-driven rodent and cell-based preclinical models with observational and interventional clinical studies. He has received funding from the National Institutes of Health and American Heart Association; authored over 50 manuscripts and over 50 abstracts in the areas of cytochromes P450, eicosanoid and drug metabolism, experimental therapeutics and pharmacogenomics; and has served as the primary research advisor for 13 postdoctoral fellows and Pharm.D./Ph.D. graduate students.

A major focus of Craig Lee’s research program is to develop a mechanistic understanding of how cytochrome P450 (CYP)-mediated metabolism of endogenous fatty acids (notably arachidonic acid) influences hepatic and extra-hepatic inflammatory responses with the expectation that these effects can be modulated in clinically relevant pathological conditions. He has demonstrated that activation of the innate immune response downregulates hepatic and extrahepatic CYP-mediated eicosanoid biosynthesis, and therapeutic restoration of CYP-derived epoxyeicosanoids (EETs) elicits potent anti-inflammatory and protective effects in preclinical models of cardiovascular and metabolic disease.

  • Theken KN, Deng Y, Kannon MA, Miller TM, Poloyac SM, #Lee CR. Activation of the acute inflammatory response alters cytochrome P450 expression and eicosanoid metabolism. Drug Metab Dispos. 2011; 39(1):22-29. [PMID: 20947618] [PMCID: PMC3014271]
  • Deng Y, Edin ML, Theken KN, Schuck RN, Flake GP, Kannon MA, DeGraff LM, Lih FB, Foley J, Bradbury JA, Graves JP, Tomer KB, Falck JR, Zeldin DC, #Lee CR. Endothelial CYP epoxygenase overexpression and soluble epoxide hydrolase disruption attenuate acute vascular inflammatory responses in mice. FASEB J. 2011; 25(2):703-713. [PMID: 21059750] [PMCID: PMC3023387]
  • Zha W, Edin ML, Vendrov KC, Schuck RN, Lih FB, Jat JL, Bradbury JA, DeGraff LM, Hua K, Tomer KB, Falck JR, Zeldin DC, #Lee CR. Functional characterization of cytochrome P450-derived epoxyeicosatrienoic acids in adipogenesis and obesity. J Lipid Res. 2014; 55(10):2124-36. [PMID: 25114171] [PMCID: PMC4174005]
  • Schuck RN, Zha W, Edin ML, Gruzdev A, Vendrov KC, Miller TM, Xu Z, Lih FB, DeGraff LM, Tomer KB, Jones HM, Makowski L, Huang L, Poloyac SM, Zeldin DC, #Lee CR. The cytochrome P450 epoxygenase pathway regulates the hepatic inflammatory response in fatty liver disease. PLoS One. 2014; 9(10):e110162. [PMID: 25310404] [PMCID: PMC4195706]

In parallel, he has led an inter-disciplinary effort to translate these mechanistically-focused preclinical discoveries into humans. The ongoing development of drugs that promote the anti-inflammatory and protective effects of EETs has underscored the need to elucidate the relationship between interindividual variation in CYP eicosanoid metabolism and cardiovascular disease risk in humans. Using functionally relevant germline genetic variants and eicosanoid metabolite biomarkers, he has identified subsets of the population predisposed to low EET levels and elevated cardiovascular disease risk and has stimulated future work in this area.

  • Lee CR, North KE, Bray MS, Fornage M, Seubert JM, Newman JW, Hammock BD, Couper DJ, Heiss G, Zeldin DC. Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study. Hum Mol Genet. 2006; 15(10):1640-49. [PMID: 16595607] [PMCID: PMC2040335]
  • #Lee CR, Pretorius M, Schuck RN, Burch LH, Bartlett J, Williams SM, Zeldin DC, Brown NJ. Genetic variation in soluble epoxide hydrolase (EPHX2) is associated with forearm vasodilator responses in humans. Hypertension. 2011; 57(1):116-122. [PMID: 21098312] [PMCID: PMC3020911]
  • Theken KN, Schuck RN, Edin ML, Tran B, Ellis K, Bass A, Lih FB, Tomer KB, Poloyac SM, Wu MC, Hinderliter AL, Zeldin DC, Stouffer GA, #Lee CR. Evaluation of cytochrome P450-derived eicosanoids in humans with stable atherosclerotic cardiovascular disease. Atherosclerosis. 2012; 222(2):530-6. [PMID: 22503544] [PMCID: PMC3361525]
  • Schuck RN, Theken KN, Edin ML, Caughey M, Bass A, Ellis K, Tran B, Steele S, Simmons BP, Lih FB, Tomer KB, Wu MC, Hinderliter AL, Stouffer GA, Zeldin DC, #Lee CR. Cytochrome P450-derived eicosanoids and vascular dysfunction in coronary artery disease patients. Atherosclerosis. 2013; 227(2):442-8. [PMID: 23466098] [PMCID: PMC3638946]

Lee has made significant contributions to an interinstitutional collaborative effort that has generated and initially characterized genetically-modified mice with endothelial overexpression of the primary human CYP epoxygenases (CYP2J2, CYP2C8) and increased endothelial EET biosynthesis. These models have significantly advanced the field by elucidating the functional role of endothelial-derived EETs in multiple pathophysiologic conditions including hypertension and renal injury, myocardial and cerebral ischemia reperfusion injury, tumor development and metastasis, wound healing and organ regeneration and metabolic disease.

  • *Lee CR, *Imig JD, Edin ML, Foley J, DeGraff LM, Bradbury JA, Graves JP, Lih FB, Clark J, Myers P, Perrow AL, Lepp AN, Kannon MA, Ronnekleiv OK, Alkayed NJ, Falck JR, Tomer KB, Zeldin DC. Endothelial expression of human cytochrome P450 epoxygenases lowers blood pressure and attenuates hypertension-induced renal injury in mice. FASEB J. 2010; 24(10):3770-81. [PMID: 20495177] [PMCID: PMC2996903]
  • Edin ML, Wang ZJ, Bradbury JA, Graves JP, Lih FB, DeGraff LM, Foley JF, Torphy R, Ronnekleiv OK, Tomer KB, Lee CR, Zeldin DC. Endothelial expression of human cytochrome P450 epoxygenase CYP2C8 increases susceptibility to ischemia-reperfusion injury in isolated mouse heart. FASEB J. 2011; 25(10):3436-47. [PMID: 21697548] [PMCID: PMC3177568]
  • *Panigrahy D, *Edin ML, *Lee CR, *Huang S, Bielenberg DR, Butterfield CE, Barnés CM, Mammoto A, Mammoto T, Luria A, Benny O, Chaponis DM, Dudley AC, Greene ER, Vergilio J, Pietramaggiori G, Scherer-Pietramaggiori SS, Short SM, Seth M, Lih FB, Tomer KB, Yang J, Schwendener RA, Hammock BD, Falck JR, Manthati VM, Ingber DE, Kaipainen A, D’Amore PA, Kieran MW, Zeldin DC. Epoxy-eicosanoids stimulate multi-organ metastasis and tumor dormancy escape in mice. J Clin Invest. 2012; 122(1):178-91. [PMID: 22182838] [PMCID: PMC3248288]
  • Panigrahy D, Kalish BT, Huang S, Bielenberg DR, Le HD, Yang J, Edin ML, Lee CR, Benny O, Mudge DR, Butterfield CE, Mammoto A, Mammoto T, Inceoglu B, Jenkins RL, Simpson M, Akino T, Lih FB, Tomer KB, Ingber DE, Hammock BD, Falck JR, Manthati VL, Kaipainen A, D’Amore PA, Puder M, Zeldin DC, Kieran MW. Epoxy-eicosanoids promote organ and tissue regeneration. Proc Natl Acad Sci U S A. 2013; 110(33):13528-33. [PMID: 23898174] [PMCID: PMC3746918]

Lee’s research program has also worked to identify and elucidate the key factors that exacerbate interindividual variability in the metabolism of and response to drugs currently on the market and determine whether implementation of genomic and biomarker-guided strategies can reduce this variability in metabolism and response and ultimately improve outcomes. His contributions to the field of precision medicine have primary occurred in the area of pharmacogenomics with a scientific focus on genetic variation in cytochrome P450-mediated drug metabolism and a clinical application focus in cardiovascular disease. This area has also been a major focus of Lee’s efforts in the area of teaching and continuing education.

  • Lee CR, Goldstein JA, Pieper JA. Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in vitro and human data. Pharmacogenetics. 2002; 12(4):251-63. [PMID: 11927841]
  • Lee CR, Pieper JA, Hinderliter AL, Blaisdell JA, Goldstein JA. Evaluation of CYP2C9 metabolic activity with tolbutamide in CYP2C9*1 heterozygotes. Clin Pharmacol Ther. 2002; 72(5):562-71. [PMID: 12426520]
  • Ellis K, Stouffer GA, McLeod HL, #Lee CR. Clopidogrel pharmacogenomics and risk of inadequate platelet inhibition: US FDA recommendations. Pharmacogenomics. 2009; 10(11):1799-1817. [PMID: 19891556]
  • Lee JA, Lee CR, Reed BN, Plitt DC, Polasek MJ, Howell LA, Cicci JD, Tasca KE, Weck KE, Rossi JS, Stouffer GA. Implementation and evaluation of a CYP2C19 genotype-guided antiplatelet therapy algorithm in high-risk coronary artery disease patients. Pharmacogenomics. 2015; 16(4):303-313. [PMID: 25823779]

Complete List of Published Work in MyBibliography

Positions and Employment

2000-present Registered Pharmacist, North Carolina, Licensure #15450

2000-2002 Clinical Research/Drug Development Fellow, co-sponsored by the UNC School of Pharmacy and GlaxoSmithKline, Inc.

2002-2006 Guest Researcher, Division of Intramural Research, NIH/NIEHS

2006-2012 Assistant Professor of Pharmacy, DPET, UNC Eshelman School of Pharmacy

2008-2016 Director of Graduate Admissions, DPET, UNC Eshelman School of Pharmacy

2012-present Associate Professor of Pharmacy (with Tenure), UNC Eshelman School of Pharmacy

2016-present Director of Graduate Studies, DPET, UNC Eshelman School of Pharmacy

Other Experience and Professional Memberships

2000-present Full Member, American College of Clinical Pharmacy (ACCP)

2002-present Full Member, American Society for Clinical Pharmacology and Therapeutics (ASCPT)

2003-present Professional Member, American Heart Association (AHA)

2006-present Member, American Society for Pharmacology and Experimental Therapeutics (ASPET)

2009-2014 Scientific Member, Institutional Review Board, NIH/NIEHS

2010-present Faculty Member, Pre-Doctoral Training Program in Integrative Vascular Biology

(T32 HL069768)

2010 Study Section Member, Special Emphasis Panel, 2010/05 ZES1 LWJ-V (01) 2

2011-present Scientific Reviewer (ad hoc), Office of Clinical Research, NIH/NIEHS

2011-present Faculty Member, UNC-Duke Collaborative Clinical Pharmacology Postdoctoral Training Program (T32 GM086330)

2012-present Co-Chair, Poster Session, International Winter Eicosanoid Conference

2013 Study Section Member, Special Emphasis Panel, 2013/08 ZRG1 BDCN-A (40)

2013-present Member, Clinical Pharmacology Committee, AHA Council on Clinical Cardiology

2014-present Member, Membership & Communications Committee, AHA Council on Functional Genomics and Translational Biology

2015-present Affiliate Member, NIH Implementing GeNomics In PracTicE (IGNITE) Network

2016-present Faculty, Postdoctoral Training Program in Genetic Epidemiology of Heart, Lung and Blood Traits (GenHLB) (T32 HL 129982)

Editorial Boards

2005-2013 Current Clinical Pharmacology

2010-present Frontiers in Vascular Physiology

2011-present Prostaglandins and Other Lipid Mediators

2012-present Frontiers in Pharmacogenetics and Pharmacogenomics


2000 Graduated with Highest Distinction and Honors, UNC School of Pharmacy

2003-2006 Ruth L. Kirschstein Individual National Research Service Award (F32), NIH/NIEHS

2005-2006 Postdoctoral Award for Research Excellence, UNC-Chapel Hill

2005 Elizabeth Barrett-Connor Research Award in Epidemiology for Young Investigators,

AHA Council on Epidemiology and Prevention

2006, 2010 Travel Award, Winter Eicosanoid Conference

2011 Junior Investigator Award, ACCP Cardiology Practice and Research Network

2011 Elected Fellow, American College of Clinical Pharmacy (FCCP)

2015 Elected Fellow, American Heart Association, Council on Clinical Cardiology (FAHA)

Ongoing Research Support

AHA 16GRNT29300003 (Grant-in-Aid)                                                Lee, CR (PI)                 7/1/16 – 6/30/18

American Heart Association, Mid-Atlantic Affiliate

Novel Biomarkers of Eicosanoid Metabolism in Coronary Artery Disease

The major goal of this project is to project is to elucidate the relationship between inter-individual variation in the cytochrome P450 epoxyeicosanoid (EET) metabolic pathway and prognosis in patients with coronary artery disease (CAD), and facilitate the development novel therapeutic strategies for CAD that target subsets of the population predisposed to low EET levels and poor prognosis.

Role: Principal Investigator

RX03512212 (Pilot Grant)                                                                    Lee, CR (PI)                 10/1/15 – 9/30/16

The Eshelman Institute for Innovation

Solving the Mystery of Highly Variable Drug Disposition in Pregnant Women: Are Unique Hepatic Drug Metabolizing Enzymes Activated during Pregnancy?

The major goal of this pilot project is to determine whether unique hepatic drug metabolizing enzymes are activated in the presence of the dramatic sex hormone changes that occur throughout pregnancy and, in turn, significantly contribute to sex hormone evoked changes in the metabolic clearance of drugs used in pregnancy.

Role: Principal Investigator


Completed Research Support

AFPE Gateway to Research Scholarship                                        Wells, MA (PI)              6/30/15 – 6/30/16

American Foundation for Pharmaceutical Education

Translational Evaluation of Cytochrome P450-Derived Eicosanoid Metabolites as a Biomarker in Non-Alcoholic Steatohepatitis (NASH) Patients

The major goal of this pilot project is to provide support for Michael A. Wells during completion of his Doctor of Pharmacy Honors research project, and facilitate his exploration of science as a future career direction.

Role: Major Advisor

R01 GM088199-01-05                                                                           Lee, CR (PI)                 8/1/09 – 5/31/15


Cytochrome P450 Derived Eicosanoids and Inflammation

The major goal of this project was to define the contribution of cytochrome P450 (CYP) derived eicosanoids to the regulation of hepatic and cardiovascular inflammatory responses in vivo, and facilitate the development of new anti-inflammatory strategies with potential therapeutic application to numerous disease states in humans.

Role: Principal Investigator

AHA 11PRE7240059 (Pre-Doctoral Fellowship)                              Schuck, RN (PI)           7/1/11 – 6/30/13

American Heart Association, Mid-Atlantic Affiliate

Translational Characterization of Arachidonic Acid Metabolism in Vascular Inflammation and Cardiovascular Disease

The major goal of this project was to provide stipend support for Robert N. Schuck during completion of his dissertation research project.

Role: Sponsor (Co-Sponsor: Cam Patterson)

R01 GM088199-S1-03-05                                                                     Lee, CR (PI)                 8/1/11 – 5/31/14


NIH Research Supplement to Promote Diversity in Health-Related Research

The major goal of this supplement to R01 GM088199 was to provide a graduate student support as he developed his dissertation research proposal and submitted an extramural fellowship application.

Role: Principal Investigator

TraCS # 550KR41202 (Pilot Grant)                        Barritt, AS & Brouwer, KL (co-PI)           1/1/13 – 6/30/14

North Carolina Translational and Clinical Sciences (NC TraCS) Institute

Altered Drug Disposition and Bile Acid Profiling as Novel Biomarkers to Predict Disease Severity in Patients with Chronic Inflammatory Liver Disease

The major goal of this CTSA-funded pilot project was to evaluate bile acids as novel biomarkers in non-alcoholic steatohepatitis (NASH) patients, and establish a biorepository that will facilitate biomarker discovery. The biorepository has facilitated an ongoing collaborative effort between Drs. Brouwer, Barritt and Lee to initially evaluate cytochrome P450-derived eicosanoids as novel biomarkers in NASH patients.

Role: Collaborator

AHA 13PRE16470017 (Pre-Doctoral Fellowship)                            Oni-Orisan, A (PI)        7/1/13 – 6/30/15

American Heart Association, Mid-Atlantic Affiliate

Soluble Epoxide Hydrolase and Cardioprotection: Translation from Mice to Humans

The major goal of this project was to provide stipend support for Akinyemi Oni-Orisan during completion of his dissertation research project.

Role: Sponsor (Co-Sponsor: Darryl Zeldin)

TraCS # 550KR61307 (Pilot Grant)                                                     Boggess, KA (PI)        3/1/14 – 2/28/15

North Carolina Translational and Clinical Sciences (NC TraCS) Institute

A Dose Escalation Study of Nicotinamide Supplementation in Early Onset Preeclampsia

The major goal of this CTSA-funded pilot project was to evaluate the safety of oral nicotinamide administration in women with early onset preeclampsia in order to guide the design of a prospective clinical trial.

Role: Co-Investigator

University of North Carolina, Chapel Hill, NC Pharm.D. 05/2000 Pharmacy
University of North Carolina, Chapel Hill, NC /GlaxoSmithKline, Research Triangle Park, NC 06/2002 Fellowship, Clinical Research / Drug Development
University of North Carolina, Chapel Hill, NC Ph.D. 08/2006 Pharmaceutical Sciences

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