Angeliki Asimaki, PhD
The Role of GSK3β in the Pathogenesis of Arrhythmogenic Cardiomyopathy
Beth Israel Deaconess Medical Center, Boston, MA
2016 Amount Awarded – $50,000
Arrhythmogenic cardiomyopathy (ACM) is a heritable myocardial disease characterized by ventricular arrhythmias and sudden death in young individuals and athletes. Analysis of myocardial samples from patients has advanced our understanding of ACM. Cardiac samples, however, are particularly difficult to obtain in children, who may be carriers of pathogenic mutations but do not manifest the disease phenotype. From previous research, buccal mucosa cells from patients with ACM exhibit similar subcellular abnormalities to the heart and can be used as a surrogate tissue for analysis. In collaboration with Dr. Dominic Abrams, Director of the Inherited Cardiac Arrhythmia Program at Boston Children’s Hospital, buccal smears from children treated and evaluated at the clinic will be collected. This study will address the following areas for the first time: 1) at which age do subcellular abnormalities first appear and how does this correlate with clinical onset of disease? 2) can mutation status be predicted simply by immunostaining a buccal smear? 3) do gene carriers with normal buccal cells show changes in response to exercise or medication? and 4) do buccal mucosa cells show abnormalities in children with dilated cardiomyopathy, and if so how does this correlate with arrhythmias? It has been shown that living buccal cells can be collected, maintained in culture and made practical for use in children. This will provide researchers with a highly valuable tool for studying the mechanisms of disease pathogenesis. Because buccal mucosa cells can be readily obtained without risk and at minimal cost, their use as a surrogate tissue for the heart may be a game-changing tool in evaluating children with inherited cardiomyopathies.