Craig Lee Lab
Craig Lee Lab
Craig Lee, Pharm.D, Ph.D. is an associate professor in the UNC Eshelman School of Pharmacy’s Division of Pharmacotherapy and Experimental Therapeutics (DPET). Our mission is to optimize drug therapy through translating experimental and clinical pharmacology discoveries into precision medicine and accelerating application of these discoveries to improve patient care.
I am trained as a clinical/translational pharmaceutical scientist with expertise in cytochrome P450 metabolism, cardiovascular experimental therapeutics, and precision medicine/pharmacogenomics. I am an active member of the UNC McAllister Heart Institute and the UNC Nutrition Obesity Research Center.
The overall objective of my research program is to improve our understanding of the central mechanisms underlying inter-individual variability in drug response as a means to develop novel therapeutic strategies that will improve public health.
The major scientific focus of our laboratory is the metabolism of drugs and eicosanoids by the cytochromes P450 enzyme system. The major therapeutic area of application of our research is cardiovascular and metabolic disease.
Our laboratory 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 drug selection and dosing strategies can reduce this variability in metabolism and response and improve patient outcomes.
Our laboratory also 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 genomics and biomarkers, we seek to translate our 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.
Our laboratory is a highly collaborative and translational research program that integrates mechanistically-driven rodent and cell-based preclinical models with observational and interventional clinical studies. We have received funding from the National Institutes of Health and American Heart Association, authored over 75 manuscripts and over 75 abstracts in the areas of cytochromes P450, eicosanoid and drug metabolism, pharmacogenomics, and experimental therapeutics, and have served as the major research advisor for three Pharm.D./Ph.D. graduate students, 13 post-doctoral fellows, and 14 professional/undergraduate students.
Ongoing research projects in our laboratory are highlighted below.
A major focus of my research program is the metabolism of endogenous fatty acids by cytochromes P450 (CYPs). In parallel to the well-described cyclooxygenase and lipoxygenase pathways, enzymes from the CYP system also synthesize biologically active eicosanoids in the cardiovascular system and constitute the “3rd pathway” of arachidonic acid metabolism. It has become increasingly recognized that CYP-derived EETs and 20-HETE regulate numerous biological processes integral to the development and progression of cardiovascular and metabolic disease, such as blood pressure, inflammation, fibrosis, ischemia/reperfusion injury, angiogenesis, myocardial/vascular remodeling, and insulin resistance. Consequently, inhibitors of soluble epoxide hydrolase (sEH) and 20-HETE biosynthesis are in development.
Using a translational approach, we seek to obtain a deeper mechanistic understanding of these biological effects, in both preclinical models and in humans, in order to identify clinical applications for therapeutic strategies that modulate CYP-mediated eicosanoid metabolism and subsets of the population most likely to derive benefit from these experimental therapeutics.
An ongoing project in the Lee lab involves studying the relationship between inter-individual variation in cytochrome P450-derived eicosanoids at the genetic and metabolite level and prognosis in human patients with coronary artery disease.
A major focus of my research program involves the implementation and evaluation of CYP2C19 genotype-guided selection of antiplatelet therapy in coronary artery disease patients. An algorithm that uses clinical factors and CYP2C19 genotype to improve precision of antiplatelet therapy selection in high-risk patients undergoing percutaneous coronary intervention was implemented at our institution in 2012. Dr. George A. Stouffer (UNC Chief of Cardiology; clinical implementation of the algorithm) and Dr. Lee (data collection and analysis) have collaborated to lead this ongoing effort. Data collection and analysis is focused on evaluating the impact of genotype and clinical factors on antiplatelet drug selection, and evaluating the impact of this strategy on clinical outcomes and cost.
In collaboration with the Pharmacogenomics and Individualized Therapy Program, we are also actively engaged in an ongoing effort that seeks to preemptively implement pharmacogenomics testing into clinical practice at our institution. We seek to accomplish this in a manner that is evidence-based, feasible, sustainable, and amenable to the collection and analysis of data that enables continuous quality improvement, dissemination of best practices, and evaluation of impact on outcomes and cost.
The NIH Implementing GeNomics In PracTicE (IGNITE) Network seeks to enhance the use of genomic medicine by supporting the development of methods for incorporating genomic information into clinical care and exploration of the methods for effective implementation, diffusion and sustainability in diverse clinical settings. The Pharmacogenomics and Individualized Therapy Program has joined the NIH IGNITE Network as an affiliate member, and is actively involved in the Pharmacogenomics Working Group. Dr. Lee serves as the UNC liaison on behalf of the institution.
Most drugs prescribed in pregnancy lack dosing information specific to this population. Dosing information is lacking, in part, because the key mechanistic factors that alter drug disposition (metabolism and transport) in pregnant women are poorly understood. This results in off-label prescribing and drug dosing, increased maternal and fetal toxicity, and reduced efficacy. Hepatic drug-metabolizing enzymes and drug transporters are integral to drug disposition. Consequently, key factors that influence hepatic drug metabolism and transport in pregnancy require systematic investigation.
Using a translational approach, ongoing projects in our laboratory seek to elucidate how and to what extent pregnancy-induced sex hormones alter hepatic metabolism and hepatobiliary disposition of clinically relevant drugs used in pregnancy that exhibit distinct clearance mechanisms in the liver. Our long-term goal is to predict pregnancy-evoked changes in hepatic drug disposition in vivo, define underlying mechanisms, and optimize drug selection and dosing in pregnant patients.
Research and Scholarship in Pharmacy pathway:
Jesse Martin, Pharm.D. candidate (class of 2019)
Melody Robbins, Pharm.D. candidate (class of 2019)
Rachel Black, Pharm.D. candidate (class of 2020)
Spenser Smith, Pharm.D. candidate (class of 2020)
Carolina Medical Student Research Program:
Melissa Klein, M.D. candidate
|Katherine Theken||2006-2011||Pharm.D., Ph.D.||Research Associate, Institute for Translational Medicine & Therapeutics, University of Pennsylvania|
|Robert Schuck||2008-2013||Pharm.D., Ph.D.||Clinical Pharmacologist, Genomics and Targeted Therapy, Office of Clinical Pharmacology, U.S. Food and Drug Administration|
|Akinyemi Oni-Orisan||2010-2015||Pharm.D., Ph.D.||Assistant Professor of Pharmacy, Department of Clinical Pharmacy, University of California-San Francisco|
|Yangmei Deng||2007-2011||M.D., Ph.D.||Research Specialist, UNC Marsico Lung Institute|
|Weibin Zha||2012-2013||B.S. Pharm., Ph.D.||Scientist, DMPK, MyoKardia, Inc.|
Clinical Research / Drug Development Fellows
|Almasa Bass||2007-2008||Pharm.D.||Medical Science Liaison, Medical Affairs Shionogi, Inc.|
|Kyle Ellis||2008-2009||Pharm.D.||Clinical Pharmacist, Duke University Hospital|
|Bryant Tran||2009-2010||Pharm.D., M.S.||Scientific Manager, Medical Affairs
|Savanna Steele||2010-2011||Pharm.D.||Associate Director, Feasibility Strategy
|Brian P. Simmons||2011-2012||Pharm.D., MSCR||Clinical Scientist,
|Robert Wittorf||2012-2013||Pharm.D.||Compliance Officer, Office of Manufacturing
and Product Quality,
U.S. Food and Drug Administration
|John Andrew Lee||2013-2014||PharmD||Senior Medical Science Liaison, Immuno-Oncology,
|Melissa Polasek||2014-2015||Pharm.D.||Associate Director, Clinical Development
|M. Alison Kannon||2006-2011||B.S.||Regulatory Associate, Clinical Protocol Office
UNC Lineberger Comprehensive Cancer Center
|Kimberly Vendrov||2011-2015||B.S.||Research Technician, School of Medicine,
University of Michigan-Ann Arbor