Dr. Sharon George leads the HEART Lab – Heart Engineering: Arrhythmia Research and Therapy Lab, in the Department of Pharmacology and Chemical Biology at the University of Pittsburgh.
The HEART Lab focuses on the role of cardiac metabolism in the development of chemotherapy-induced cardiotoxicity. Impaired metabolism is a hallmark of cardiotoxicity associated with several classes of chemotherapeutic agents. Yet, there are currently no effective cardioprotective strategies to protect the heart. The research in our lab focuses on two methods of cardioprotection by preserving metabolism, (1) exercise, and (2) molecular targets of metabolism.
1. Cardio-Oncology: Our group is studying molecular targets in the heart that can be activated to prevent chemotherapy-induced metabolic impairment. This new direction of research includes both mouse and human heart models. Transgenic knockout and overexpression mouse models and pharmacological agonists and antagonists are being tested in study.
2. Sex-specific mechanisms of cardiac diseases and therapy: A preponderance of recent evidence suggests that cardiac physiology and the progression of cardiac pathophysiology is sex-specific. Premenopausal women are at a lower risk of developing life threatening cardiovascular diseases compared to age-matched men. This phenomenon is typically attributed to the protective effects of estrogen, which is higher in premenopausal women. The HEART Lab aims to understand the contribution of the sex hormones, estrogen, progesterone and testosterone, in modulating cardiac physiology and pathophysiology.
3. Human Cardiac Organotypic slices: The HEART Lab works with human donor hearts that are not used in transplantation. These human hearts can be used as whole heart preparations, coronary perfused wedge preparations and organotypic cardiac slice preparations, to study human cardiac physiology and pathophysiology. Of particular interest to the HEART Lab is the organotypic cardiac slices which are generated from the atria or ventricles in the heart at a thickness of up to 400 microns. These slices contain cardiomyocytes in their native environment along with other cardiac cell types and are an excellent tool for preclinical drug testing and translation of findings from animal research to the clinic. Dr. George has used this platform to test the effects of cancer chemotherapeutic agents such as doxorubicin, sunitinib, and other drugs such as dantrolene and relaxin.
4. Multi-parametric optical mapping of cardiac physiology and pathophysiology: Optical mapping is an imaging technique used to measure cardiac function from living tissue which can range from cells to whole hearts. To study the complex, multi-faceted phenomenon that is cardiac physiology and pathophysiology, the HEART Lab uses multi-parametric imaging systems to simultaneously measure parameters of cardiac metabolism (NADH and FAD), excitation (transmembrane potential) and contraction (intracellular calcium transients) from the same field of view. This allows the study of the modulation of these individual parameters and the interrelationship between them called metabolism-excitation-contraction coupling (MEC coupling).