Show-Ling Shyng, PhD

Show-Ling Shyng

Shyng Lab Research

We are interested in understanding ion channel regulation in health and disease.  Specifically, our research focuses on ATP-sensitive K+ (KATP) channels, which link cell metabolism to membrane excitability and have important physiological functions including regulation of hormone secretion, protection of the heart and the brain against ischemic injuries, and control of vascular tone. Genetic variations in the KATP channel genes have been linked to several human diseases including congenital hyperinsulinism,neonatal diabetes, DEND (Developmental delay, Epilepsy, and Neonatal Diabetes) syndrome, dilated cardiomyopathy, and Cantu syndrome. Our efforts are directed towards understanding the structural and molecular basis of KATP channel biogenesis, trafficking, and gating, and how mutations in the channel genes disrupt channel biology to cause diseases. The ultimate goal is to translate basic science findings to disease treatment by developing mechanism-based therapeutic strategies.

Several projects are currently underway. One is to investigate KATP channel structures and mechanisms of gating using electrophysiology, single particle cryo-EM,and crosslinking mass spectrometry. A second project aims to understand the structural and cellular mechanisms that govern channel protein folding, assembly, and degradation, and to identify pharmacological chaperones that correct channel biogenesis and trafficking defects caused by disease mutations,using biochemical, proteomic, and chemical biology approaches. A third project is to study how the adipocyte-derived hormone leptin regulates the trafficking of KATP channels in pancreatic β-cells and hypothalamic neurons to control glucose and energy homeostasis. Using biochemical, electrophysiology, live cell imaging, and phosphoproteomic strategies, we are exploring the signaling pathway underlying the effect of leptin, in particular the role of NMDA receptors in mediating the effect of leptin to activate the downstream molecule AMPK, and how AMPK activation leads to actin reorganization to regulate channel trafficking.

 

Link to PubMed Listing

Dr. Shyng's NIH Biosketch