Assistant Professor Graduate Institute of Biotechnology
Chinese Culture University
My major research interest is to understand the underlying mechanisms of cardiac diseases such as arrhythmias, and the molecular and cellular basis for potential treatment of cardiac diseases. I am identifying and investigating a novel mechanism (tyrosine phosphorylation) to correct the membrane trafficking defect of the Hyperpolarized Cyclic-Nucleotide gated (HCN) channel mutant that are found in patients with cardiac long QT symptoms. Currently, the major approaches that I am employing include electrophysiology (patch clamp recording), calcium imaging, protein biochemistry (immunoprecipitation and Western blotting analyses), as well as animal surgery (whole rat or mouse cathetering and drugs administration) (J. Biol. Chem. 284: 30433-30440, 2009).
To further examine a novel role of tyrosine phosphorylation in the arrhythmogenesis in whole animal system, I also established a rat arrhythmia model without structural remodeling. Using rats as the animal model and selective inhibitors, I specifically studied the roles of Src tyrosine kinase activity and protein tyrosine phosphatase activity in the altered electrophysiology using animal surgery cathetering (in which left ventricle pressure and blood pressure can be monitored) and electrocardiography (ECG) technique. By using sodium orthovanadate, a selective inhibitor of protein tyrosine phosphatases, we found that several typical types of ventricular arrhythmias can be generated, demonstrating a significant role of tyrosine phosphorylation in ventricular arrhythmogenesis.