Mario Delmar, MD, PhD

Medicine (Cardiology) - Primary Mentor

The mechanisms responsible for ventricular arrhythmias in patients with cardiomyopathies are poorly understood. It is the long-term objective of our laboratory to gain knowledge on how disruption of mechanical function can alter the electrical stability of the heart. Our research focuses on the interactions occurring at the intercalated disc. Specifically, we study the cross-talk between molecules involved in mechanical coupling (desmosomes; adherens junctions) and those involved in the propagation of electrical signals between cells (gap junctions; sodium channels). It is our central hypothesis that rather than independent, these complexes closely interact with one another, so that loss of mechanical integrity can lead to electrical dysfunction and arrhythmias. These studies require a multi-disciplinary approach involving biochemistry, cellular and multicellular electrophysiology, microscopy and molecular biology. Our studies seek translation into the molecular mechanisms responsible for lethal arrhythmias in patients afflicted with arrhythmogenic right ventricular cardiomyopathy (ARVC), an inherited disease associated with sudden death in the young and linked to mutations in proteins of the cardiac desmosome, a structure responsible for mechanical continuity between cardiac cells.