Projects
We seek to understand the form and function of the cardiac conduction system, and develop treatments for heart rhythm-associated diseases.
reprogramming of nodal pacemaker cells
We seek to understand the cellular events that take place during heart pacemaker (i.e., nodal) cell development and reprogramming. The emphasis is on investigating how the heart’s natural pacemaker tissue self-organizes to achieve its exquisite form and function. The research tools of our investigation include cardiac electrophysiology at the level of single myocytes, tissue constructs, whole-heart and small animal models. The new knowledge are applied to bioengineer cardiac pacemaker organoids. The biological pacemakers are designed to create natural heart rhythm, recapitulating the natural heart rhythm that we are born with.
Lineage patterning of human pluripotent stem cells
The goal of this project is to understand the molecular mechanisms of cardiac chamber-specific differentiation of human ES and iPS cells. The insights gained are translated to develop generalizable methods to derive cardiac myocytes of the nodal, atrial and ventricular subtypes. The emphasis is on dissecting electrophysiological properties of the de novo human cardiac myocytes in a longitudinal manner. Viral and non-viral gene transfer modalities are employed to impose gain/loss of function on the stem cells, and study their consequences in vitro and upon transplantation in vivo.
Preclinical models of cardiac arrhythmias
We develop large animal models of cardiac arrhythmias that serve as the proving ground for our gene and cell-based therapies. We work side by side with clinicians to engage in translational projects toward gene- and cell-based therapies for heart rhythm-associated diseases and cardiac regeneration. The project is aimed at evaluating the clinical efficacy and safety of our biologics in clinically-relevant large animals models. Our explicit goal is to develop paradigm-changing therapies for patients with congenital heart diseases so that device-dependent children and adults can not only survive, but thrive.