Lab Website: https://song.lab.uiowa.edu/

Molecular mechanisms of heart failure, arrhythmias, obesity and diabetes

Research in our 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 our 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; Wang JACC-BTS 2018); and 2) mis-trafficking of junctophilin-2 to the cell periphery mediated by microtubule densification (Zhang Circulation 2014). Very recently, we made a novel 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). We will continue our endeavor in investigating the structure and function of junctophilin-2 in the heart, and its therapeutic potential for treating heart failure and arrhythmias.

PubMed link

Department/Program Affiliations:
Internal Medicine