We identified OCaR2 as a regulator of lysosomal two-pore channels, and its deletion resulted in Ca2+ oscillations in cardiomyocytes causing fatal catecholaminergic arrhythmias. We combine Ca2+ imaging, ECG telemetry, transcriptome and metabolome approaches with computational methods to elucidate pathways and patterns of gene regulation. By comparative analysis of circuits in arrhythmogenic cardiomyopathy models, we aim to determine common molecular circuits in the pathogenesis of catecholamine driven ventricular arrhythmias.
