Craig Lee’s research interests include the role of genomics in the development, progression and treatment of cardiovascular disease, with a focus on eicosanoid metabolism, inflammation and endothelial dysfunction.
Craig Lee Lab
I am an associate professor in the UNC Eshelman School of Pharmacy’s Division of Pharmacotherapy and Experimental Therapeutics (DPET). The mission of DPET 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.
I am also a member of the UNC McAllister Heart Institute, UNC Center for Pharmacogenomics and Individualized Therapy and UNC Nutrition Obesity Research Center.
The overall objective of my research program is to improve our understanding of the key mechanisms underlying inter-individual variability in drug response as a means to develop novel therapeutic strategies that will improve public health. The focus of my research program is twofold. First, we seek 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, 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. Second, we seek 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.
Over the past decade, I have established a highly collaborative and translational research program that integrates mechanistically-driven rodent and cell-based preclinical models with observational and interventional clinical studies. I have received funding from the National Institutes of Health and the 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 have served as the primary research advisor for 10 post-doctoral fellows, 3 Pharm.D./Ph.D. graduate students and 8 Pharm.D. students.
The 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 experiment therapeutics.
- Lee CR, Lead Innovator, Solving the Mystery of Highly Variable Drug Disposition in Pregnant Women: Are Unique Hepatic Drug Metabolizing Enzymes Activated during Pregnancy? Sponsored by The Eshelman Institute for Innovation
- Lee CR, Co-Principal Investigator, Evaluation of New Biomarkers of Acute Coronary Syndromes and Atherosclerotic Cardiovascular Disease in Patients Undergoing Coronary Angiography (Co-Principal Investigator, George A. Stouffer, UNC Division of Cardiology).
- Lee CR, Co-Principal Investigator, Retrospective Study of CYP2C19 Genotype and Anti-Platelet Therapy in a Cardiac Catheterization Lab Population (Co-Principal Investigator, George A. Stouffer, UNC Division of Cardiology).
- Lee CR, Co-Investigator, The Role of the Functionally Relevant Single Nucleotide Polymorphisms CYP2J2 -50G>T (CYP2J2*7) and EPHX2 9846A>G (EPHX2 K55R) in Human Endothelial Function: the Environmental Polymorphism Registry, sponsored by NIEHS/NIH (Principal Investigator, Darryl C. Zeldin, NIEHS/NIH).
- Lee CR, Co-Investigator, A Dose Escalation Study of Nicotinamide Supplementation in Early Onset Preeclampsia (Principal Investigator, Kim A. Boggess, UNC Department of Obstetrics and Gynecology).
|Katherine Theken||2006-2011||Pharm.D., Ph.D.||Postdoctoral Fellow, 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.||Postdoctoral Fellow, Clinical Pharmacology, 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.||Postdoctoral Fellow, School of Pharmacy, University of Washington|
Clinical Research / Drug Development Fellows
|Almasa Bass||2007-2008||Pharm.D.||Manager, Clinical Research
|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 Associate,
|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||Medical Science Liaison, Immuno-Oncology, Bristol-Myers Squibb / The Medical Affairs Company|
|Melissa Polasek||2014-2015||Pharm.D.||Drug Development Fellow / Quintiles|
|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|