Decoding the Cell-Cell Junction to Uncover New Pathways and Therapies for Arrhythmogenic Heart Disease
Translational Cardiovascular Research Center (TCRC) monthly seminar presents:
"Decoding the cell-cell junction to uncover new pathways and therapies for arrhythmogenic heart disease"
The TCRC monthly seminar series covers diverse topics in translational cardiovascular research.
Abstract: Arrhythmogenic cardiomyopathy (AC) is an untreatable genetic-based heart disease, classically characterized by early electrical (remodeling) defects, exemplified by a high frequency of ventricular arrhythmias, which can be exacerbated with exercise, leading to sudden cardiac death. However, structural defects are equally important as AC hearts are characterized by fibro-fatty replacement of the myocardium, which leads to ventricular dysfunction and classic heart failure. Human genetic studies show that 40-50% of AC patients carry mutations in genes encoding components of the desmosomal cell-cell junction, thus termed a cardiac “disease of the desmosome. However, the precise mechanisms driving desmosomal cell-cell junction destruction and disease, especially in the context of patient genetics remains poorly understood. In addition, there remain no interventions to treat AC. Using a combination of unbiased (yeast-based) protein-protein interaction screens, novel genetic mouse models, human cardiac stem cell model systems and gene therapy approaches, we have uncovered new molecular players that intersect with protein degradative pathways that underlie AC pathogenesis as well as uncover new clinically relevant approaches that would be most impactful in treating AC patient populations.
Dr. Sheikh is a professor in the Department of Medicine at the University of California – San Diego School of Medicine. Her laboratory is focused on uncovering mechanisms underlying biomechanical stress responses in the heart, which play a central role in the pathology of human heart disease. She has exploited genetic mouse models to uncover novel signaling and cytoskeletal components that drive the pathogenesis of dilated cardiomyopathy, hypertrophic cardiomyopathy and heart failure progression. Dr. Sheikh is also a co-founder of multiple early-stage biotech companies and with a recent acquisition of one of her companies, is advancing gene-therapy based treatment approaches for arrhythmogenic cardiomyopathy populations. Her lab is currently supported by the National Institutes of Health, the Department of Defense and industry grants.