Research in the Song laboratory aims to understand the cellular and molecular mechanisms that causes heart failure and arrhythmias. In particular, we are interested in unraveling the novel functions of the E-C coupling structure protein junctophilin-2 in heart cells and its implications in these heart diseases. Work from the Song laboratory has established a new paradigm for heart failure development and progression by linking junctophilin-2 dysregulation to cardiomyocyte T-tubule ultrastructural remodeling and E-C coupling dysfunction (Song PNAS 2006; Wei Circ Res 2010; Guo PNAS 2014; Zhang Circulation 2014, among other original contributions). Furthermore, we have unraveled two distinct mechanisms underlying junctophilin-2 dysregulation: 1) proteolysis of junctophilin-2 by calpain (Wu JAHA 2014; Guo JBC 2015); and 2) mis-trafficking of junctophilin-2 to the cell periphery mediated by microtubule densification (Zhang Circulation 2014). Very recently, we made a major discovery that the E-C coupling structural protein junctophilin-2 encodes a stress-adaptive transcriptional regulator, which serves as an important protective mechanism in antagonizing pathological remodeling in response to cardiac stress (Guo Science 2018, link for full article). We will continue our endeavor in investigating the novel functions of junctophilin-2, and its therapeutic potential for treating heart failure and arrhythmias.

 

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