Jim Jung-Ching Lin, Ph.D.

Research

Intercalated discs (ICDs) are cardiac-specific structures responsible for mechanical and electrical communication among adjacent cardiomyocytes and are implicated in signal transduction. The striated muscle-specific Xin repeat-containging proteins localize to ICDs and play critical roles in ICD formation and cardiac function. Knocking down the Xin gene in chicken embryos collapses the wall of developing heart chambers and leads to abnormal cardiac morphogenesis. In mammals, a pair of paralogous genes, Xinalpha (Xirp1) and Xinbeta (Xirp2) exist. Ablation of the mouse Xinalpha (mXinalpha) does not affect heart development. Instead, mXinalpha-deficient hearts up-regulate mouse Xinbeta (mXinbeta), suggesting a partial compensatory role of mXinbeta. Complete loss of mXinbeta, however, leads to failure of forming ICD, mis-localization of mXinalpha, diastolic dysfunction, and early postnatal lethality. We are investigating the underlying mechanisms leading to cardiomyopathy and heart failure.