Cardiovascular Biology

The Laboratory of Cardiovascular Biology, led by Dr. Leslie Kennedy, investigates pathways and mechanisms that can be exploited to ultimately benefit patients prone to cardiovascular pathologies.

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Leslie

Senior Investigator Research Interests

Research Interests

Ischemic heart disease is a leading cause of death in the U.S.  Cardiomyocytes (CMs) derived from induced pluripotent stem cells (iPSCs) have been studied as a therapy to improve cardiac function following acute or chronic ischemia. However, the CMs derived from iPSCs are very immature, which has severely hampered their use as both a therapy and as a model system to study cardiac disease. As a result, there is great interest in better understanding the mechanisms responsible for CM maturation. Our work focuses on identifying novel regulators of CM maturation, establishing mechanisms by which these proteins function in CM maturation, and assessing improvements in maturation that result from perturbing expression or function of these proteins.

Failing human hearts have a well-known signature of re-expressing fetal genes and reverting to a more fetal metabolic program. As we identify novel players in CM differentiation and maturation, there is potential for these proteins to be up- or down-regulated in the failing myocardium. Therefore, we are also interested in exploring roles for these newly-described proteins in the failing heart. Ultimately, these investigations into CM differentiation, maturation, and fetal reversion are important for identifying druggable targets with therapeutic potential.

Featured Publications

Ogfod1 deletion increases cardiac beta-alanine levels and protects mice against ischemia-reperfusion injury.

Authors: Harris M, Sun J, Keeran K, Aponte A, Singh K, Springer D, Gucek M, Pirooznia M, Cockman ME, Murphy E, Kennedy LM.
Cardiovasc. 2021 Oct 20:cvab323
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ALKBH7 mediates necrosis via rewiring of glyoxal metabolism.

Authors: Kulkarni CA, Nadtochiy SM, Kennedy L, Zhang J, Chhim S, Alwaseem H, Murphy E, Fu D, Brookes PS.
Elife. 2021 Aug 14;9:e58573
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The ribosomal prolyl-hydroxylase OGFOD1 decreases during cardiac differentiation and modulates translation and splicing.

Authors: Stoehr A, Kennedy L, Yang Y, Patel S, Lin Y, Linask KL, Fergusson M, Zhu J, Gucek M, Zou J, Murphy E.
JCI Insight 2019 May 21;5(13):e128496
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Meet the Team

Leslie

Leslie Kennedy, Ph.D.

Investigator and Independent Research Scholar

Dr. Leslie Kennedy was born and raised in Charlotte, NC. In 2008, Dr. Kennedy earned her B.S. in Biology with honors from Elizabeth City State University, where she was awarded the Chancellor’s Distinguished Emblem Award and the Honors Program Merit Award. She then accepted a position as a laboratory manager in the Lineberger Comprehensive Cancer Center of the University of North Carolina at Chapel Hill. Dr. Kennedy then earned her Ph.D. in Biology from the University of North Carolina at Chapel Hill in 2017 just prior to coming to the NHLBI in 2017 as a postdoctoral fellow working in the laboratory of Elizabeth Murphy, Ph.D. Within 3 years of beginning a fellowship at the NHLBI, Dr. Kennedy has won the NHLBI’s Lenfant Biomedical Fellowship Award and has been named an NIH Independent Research Scholar, which transitioned her from her postdoctoral fellowship to her current faculty position. Dr. Kennedy’s work focuses on investigating the molecular underpinnings of cardiovascular pathologies, such as heart failure and hypertrophic cardiomyopathy.

Alumni

Michael Harris

Postbaccalaureate Fellow