My laboratory is interested in understanding the mechanisms that contribute to the development of heart disease.
The heart functions as a pump that cycles between contraction and relaxation in order to provide nutrients and oxygen and remove waste from all organs. Multiple risk factors are known to cause malfunctions of the heart, including diabetes, obesity, aging and ischemic heart disease (heart attack). Our lab focuses on how metabolic disorders, specifically diabetes, lead to these malfunctions. We induce diabetes in mice and measure contraction and relaxation functions with ultrasound to trace what goes awry in diabetic hearts.
A number of theories have been proposed on how metabolic disorders contribute to the development of heart disease. We focus on an emerging area of research centered on a molecule called NAD+. NAD+ is a crucial part of our cellular metabolism and acts as a moderator of metabolic processes. For example, as cells break down sugar and fat for energy, NAD+ is a critical facilitator for the flow of these metabolic processes.
Studies from the past decade have started to expand our understanding on how this molecule regulates other cellular processes and, ultimately, contributes to heart disease.
NAD+-dependent pathways have emerged as promising therapeutic targets in multiple diseases. Our goal is to identify novel NAD+-dependent mechanisms that contribute to the pathogenesis of heart disease. We hope that our studies will result in improved treatment options for patients to slow, reduce or even prevent disease progression.
Our laboratory studies how metabolism affects pathogeneses of heart and mitochondrial diseases. We are particularly interested in the emerging roles of NAD+ metabolism in these diseases. Recent studies highlight the importance of NAD+-dependent pathways in mitochondrial and cellular functions, disease pathogeneses and therapeutics. Our goal is to discover how NAD+ metabolism is involved in disease pathogenesis and to use knowledge gained to improve therapeutic strategies.
Diabetes, hypertension and aging are important risk factors for the progression of heart failure. We recently described the roles of NAD+ redox imbalance in promoting heart failure progression induced by chronic pressure overload (a hypertension model). Our laboratory now focuses on determining the roles of NAD+ metabolism in cardiac dysfunction induced by metabolic disorders such as diabetes. Using multi-omics analyses and genetic models targeting NAD+ metabolism, we will dissect how NAD+ metabolism plays important roles in cardiac dysfunction induced by diabetes, and by other risk factors of heart failure.
Our laboratory also works on understanding how NAD+ metabolism contributes to the pathogenesis of mitochondrial disease, e.g. Leigh syndrome. Patients with Leigh syndrome harbor mutations in mitochondrial genes and manifest neurometabolic disorders, cardiomyopathy and early death. We recently showed that elevations of NAD+ levels improve lifespan and healthspan in a mouse model of Leigh syndrome. Using the tools and models targeted for NAD+ metabolism, we hope to identify disease mechanisms and to further improve therapeutic strategies in treating mitochondrial disease.
Senior Fellow, University of Washington, Seattle, WA, 2016
Ph.D., University of Texas Health Science Center, San Antonio, TX, 2011
M.Phil., Chinese University of Hong Kong, 2004
B.Sc., Chinese University of Hong Kong, 2002
Honors and Awards
2018 New Investigator Travel Award, BCVS Scientific Sessions, American Heart Association
2017-2019 Scientist Development Grant, Association-Wide, AHA
2015 Finalist, Melvin L. Marcus Young Investigator Award, Council of Basic Cardiovascular Sciences, AHA
2015 Scholarship, Keystone Symposia
2013 BCVS Abstract Travel Award, AHA Scientific Sessions
2013-2015 Postdoctoral Fellowship, AHA Western States Affiliate
2011 ATVB Travel Award, AHA Scientific Sessions
2011 ASBMB Travel Award, Experimental Biology
2010 Finalist, Presidential Award, the Society of Leukocyte Biology
2010 Travel Award, Annual Meeting of the SLB
2010-2012 Predoctoral Fellowship, AHA Southwestern Affiliate
2011-present Council of Basic Cardiovascular Sciences, AHA
2011-present American Society of Biochemistry and Molecular Biology
2017-present American Physiological Society, Cardiovascular Section
Joined OMRF Scientific Staff in 2019
Chavez JD, Lee CF, Caudal A, Keller A, Tian R, Bruce JE. Chemical Crosslinking Mass Spectrometry Analysis of Protein Conformations and Supercomplexes in Heart Tissue. Cell Syst 6:136-141.e5, 2018 January, PMID: 29199018, PMCID: PMC5799023
Chiao YA, Chakraborty AD, Light CM, Tian R, Sadoshima J, Shi X, Gu H, Lee CF*. NAD+ redox imbalance in the heart exacerbates diabetic cardiomyopathy. Circ. Heart Fail., Accepted. * Corresponding author.
Lee CF, Caudal A, Abell L, Nagana Gowda GA, Tian R. Targeting NAD+ metabolism as interventions for mitochondrial disease in a Leigh Syndrome Mouse Model. Sci Rep 2019 Feb 28;9(1):3073. PMID: 30816177 PMCID: PMC6395802
Schweppe DK, Chavez JD, Lee CF, Caudal A, Kruse SE, Stuppard R, Marcinek DJ, Shadel GS, Tian R, Bruce JE. Mitochondrial protein interactome elucidated by chemical cross-linking mass spectrometry. PNAS, 2017;114(7):1732-1737. PMID: 28130547 PMCID: PMC5321032
Lee CF, Chavez JD, Garcia-Menendez L, Choi Y, Roe ND, Chiao YA, Edgar JS, Goo Y, Goodlett D, Bruce JE, Tian R. Normalization of NAD+ redox balance as a therapy for heart failure. Circulation, 2016;134:883-94. PMID: 27489254, PMCID: 5193133
Lee CF, Tian R. Mitochondrion as a target of heart failure therapy: the role of protein lysine acetylation. Circulation Journal, 2015;79(9):1863-70. PMID: 26248514
Karamanlidis G, Lee CF, Garcia-Menendez L, Kolwicz SC, Jr., Suthammarak W, Gong G, Sedensky MM, Morgan PG, Wang W, and Tian R. Mitochondrial complex I deficiency increases protein acetylation and accelerates heart failure. Cell Metabolism. 2013;18(2):239-50. PMID: 23931755, PMCID: PMC3779647
Cardiovascular Biology Research Program, MS 45
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-1703, (405) 271-1704
Fax: (405) 271-7417