Myocyte Biology / Heart Failure Program

Co-Directors: Dr. Lee Sweeney and Dr. Ken Margulies

The myocyte biology and heart failure research program unit is focused on elucidating the pathophysiology of myocardial remodeling and the syndrome of congestive heart failure. This program unit encompasses basic, translational and clinical research activities performed by individuals and teams from a variety of disciplines. Together these components are designed to encourage and facilitate inquiries elucidating the genetic and environmental mechanisms contributing to variations in disease progression, clinical manifestations and therapeutic responses observed in patients with heart failure.

Our thematic focus on myocardial remodeling includes post-infarction remodeling, valvular heart disease, reverse remodeling and targeted therapeutics to modulate these processes. Other prominent research themes include regulation of myocardial contractility, molecular genetics of hypertensive heart disease, transcriptional control of myocardial adaptations, biology of endogenous myocardial repair, myocardial gene therapy and heart failure disease management. Targeting therapeutic strategies based on improved understanding of disease mechanisms and distinctions among patients’ genotypes or phenotypes represents a common feature of these diverse inquiries.

The basic and translational laboratories within this program unit include established expertise and infrastructure in the areas of myocardial physiology, preclinical pharmacology and device testing, animal models of hypertrophy and heart failure, transcriptional profiling, and molecular genetics. A diverse array of established rodent and large animal models of acquired heart disease coupled with extensive in vitro and in vivo phenotyping capacity permits inquiries related to virtually any area of myocardial biology.

Core laboratories housed within this program unit include a Cardiac Myocyte Core, an Animal Surgery and Cardiovascular Physiology Core, and a Genomics/Genotyping Core. There is also an extensive human heart tissue and blood biorepository linked to a relational database that empowers human tissue research within and beyond this program unit.

Complementing the preclinical research expertise and resources is a large clinical research enterprise that is spatially and conceptually integrated with the clinical heart failure and transplant program at Penn. In addition to involvement with a wide variety of clinical trials and registries, our clinical research enterprise includes a unique and growing cohort study, The Penn Heart Failure Study, which is dedicated to elucidating modifiers of disease progression though multifaceted characterization and longitudinal follow-up of patients diagnosed with HF.

Active collaborations with the electrophysiology, cardiothoracic surgery, cardiac imaging and nursing research programs at Penn further extend the scope of the clinical research enterprise. In addition, our center leads EPHRA, a regional research consortium of six large heart failure centers in eastern Pennsylvania and New Jersey that are cooperating to facilitate and execute heart failure clinical research.