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Dr. Kelly’s research career began with deciphering the genetic basis of inborn errors in metabolism in children, followed by a series of breakthrough discoveries relevant to the diagnosis and treatment of common forms of heart failure in the general population.
Dan Kelly is the Willard and Rhoda Ware Professor of Medicine at the University of Pennsylvania Perelman School of Medicine and Presidential Professor at Children's Hospital of Philadelphia.
Dr. Kelly’s research interests stem from an early fascination with rare inborn errors in energy metabolism that cause childhood sudden death and heart failure. He defined the genetic basis for a common inborn error in mitochondrial fatty acid oxidation, work that led to the development of practical newborn screening tests. Thereafter, he became interested in how similar derangements in cardiac fuel and energy metabolism contribute to acquired forms of heart failure in adults. The Kelly Laboratory has recently identified several candidate therapeutic targets to re-balance mitochondrial metabolism in heart failure.
Dr. Kelly trained in Medicine and Cardiology at Barnes Hospital, then joined the faculty of Washington University School of Medicine where he ultimately served as Professor of Medicine and Pediatrics, Chief of the Cardiovascular Division, and the founding Director of the Center for Cardiovascular Research. In 2008, Dr. Kelly assumed the role of founding Scientific Director for the Sanford Burnham Prebys Medical Discovery Institute in Florida followed by his recruitment to serve as Director of the Penn Cardiovascular Institute. In August 2017, he moved to the University of Pennsylvania to lead the Penn Cardiovascular Institute. In 2022, Dr. Kelly assumed the role of founding Director of the CHOP CVI.
Dr. Kelly served as an Associate Editor for The Journal of Clinical Investigation and is currently on many additional editorial boards. He is a member of the American Society for Clinical Investigation (Council, 2002-05), the Association of American Physicians (AAP; President, 2022), and is a recipient of the AHA Distinguished Achievement Award and Basic Research Prize.
Education and Training
BS, University of Illinois (Biology), 1978
MD, University of Illinois College of Medicine, 1982
Internship in Medicine, Barnes Hospital, 1982 – 1983
Assistant Resident in Medicine, Barnes Hospital, 1983 – 1985
Research Postdoctoral Fellowship, Department of Biological Chemistry, Washington University School of Medicine, 1985 – 1987
Clinical Cardiology Fellow, Washington University School of Medicine, 1987 – 1989
Titles and Academic Titles
Founding Director, Children’s Hospital of Philadelphia Cardiovascular Institute
CHOP Presidential Chair
Professor of Pediatrics, CHOP and Perelman School of Medicine, University of Pennsylvania
Director, Penn Cardiovascular Institute
Willard and Rhoda Ware Professor of Medicine, Perelman School of Medicine, University of Pennsylvania
American Society for Clinical Investigation (ASCI) (1997-present)
Association of American Physicians (2001- present; President, 2022-2023)
Association of University Cardiologists (2001- present)
Fellow, American Heart Association (1999 - present)
Board of Directors, Sarnoff Cardiovascular Research Foundation (2007-2010)
Fellow, International Society for Heart Research (2010 - present)
American Diabetes Association (2014-present)
Endocrine Society (2014-present)
Heart Failure Society of America (2015-present)
Lucille P. Markey Scholar Award, Markey Foundation, 1989
Basal O’Connor Scholar Award, March of Dimes, 1991
AHA Established Investigator Award, 1995
AFCR (Midwest) Outstanding Investigator Award, 1996
AHA, Distinguished Achievement Award (Basic Cardiovascular Sciences Council), 2008
AHA, Basic Research Prize, 2009
Orlando Business Journal, CXO Executive Award, 2015
Probing the Cardiac PGC-1 Regulatory Cascade
NHLBI, 1998 - 2025
This project is designed to identify and characterize metabolic gene regulatory pathways linked to the PGC-1 transcriptional regulatory cascade during cardiac maturation and in the failing heart. Emphasis is placed on the ERR cardiac nuclear receptor transcription factor family.
PI: Daniel Kelly
Probing the Role of Mitochondrial Short-chain Carbon Homeostasis in the Hypertrophied and Failing Heart
NHLBI, 2016 - 2025
The goal of this multi-PI project is to investigate the mechanisms involved in derangements in mitochondrial fuel metabolic flux during development of heart failure using proteomic and metabolomic strategies. The impact of these mitochondrial re-programming events on the fuel and energy metabolic derangements that contribute to heart failure will be explored in well-defined mouse models.
PIs: Daniel Kelly and Deborah Muoio
Targeting Ketone Metabolism as a Novel Heart Failure Therapy
NHLBI, 2020 - 2024
In this project, we will investigate the effects of re-balancing altered cardiac fuel utilization using ketone supplementation therapies with the long-term goal of developing novel metabolic modulator therapies aimed directly at the heart during the early stages of this disease. We will also investigate the mechanism of action whereby ketone bodies benefit heart failure.
PIs: Daniel Kelly and Fabio Recchia
Probing the Cardiac Benefits of SGLT2 Inhibitor Therapy
Amgen, 2021 - 2023
The objectives of the proposal are to: 1) assess the effects of SGLT2i on cardiac function and remodeling in small models of HFrEF and HFpEF; 2) determine the role of re-balancing myocardial substrate utilization in the beneficial effects of SGLT2i in HFpEF and HFrEF; 3) define the tissue of action of SGLT2i in heart failure using knockout models in mice; and 4) identify candidate extra-cardiac mediators of SGLT2i benefits in HF using genomic and metabolomic profiling.
PI: Daniel Kelly
Abramson Cancer Center Support Grant – Metabolomics Shared Resources
NCI, 2020 - 2027
The mission of the Metabolomics Core is to provide ACC members with a world-class metabolite profiling platform to assist with new discoveries and insight into cellular metabolic mechanisms relevant to cancer. The results will be integrated with genetics, epigenetics, cell signaling interrogations.
PI: Robert Vonderheide
Advanced Cardiac Therapies for Heart Failure Patient
CHOP Frontier Program, 2022-2023
PIs: J. Rossano, K. Maeda, Z. Arany, Co-I, Daniel Kelly.