A08: Dysregulation of mRNA decay in MYBPC3 hypertrophic cardiomyopathy

In hypertrophic cardiomyopathy (HCM), the underlying mutations frequently affect MBPC3 and cause premature termination of MBPC3 protein synthesis. We observed that nonsense-mediated mRNA decay (NMD) activation plays an important role in the pathogenesis of HCM. Here we propose to (I) investigate the effect of NMD activation on gene regulation in healthy and diseased human induced pluripotent stem cells (iPSC-CMs), (II) evaluate the functional relevance of NMD activation in genetic HCM mouse models, and (III) explore a more general role of NMD in the pathogenesis of other hereditary cardiomyopathies.

PrincipAL InvestigatorS

Dr. Timon Seeger, University Hospital Heidelberg, Heidelberg University

Prof. Dr. Georg Stoecklin, University Hospital Mannheim, Heidelberg University