Show-Ling Shyng received her B.S. in Zoology in 1984 from the National Taiwan University and her Ph.D. in Neurobiology and Behavior in 1990 from Cornell University. After spending a year as a postdoctoral fellow at the California Institute of Technology, Shyng moved to Washington University where she was a research associate, and then a research assistant professor in the Department of Cell Biology and Physiology. She joined CROET as an Assistant Scientist in 1999.

Our laboratory is interested in understanding how ion channels function at the molecular level. The current focus is on the ATP-sensitive postassium channels (KATP channels). KATP channels are the molecular sensors that link cell metabolism to cell excitablility. They play important roles in a wide variety of tissues. They control insulin secretion, are involved in the response to cardiac and cerebral ischaemia, regulate smooth muscle tone, and modulate neurotransmitter release at synapses. KATP channels are regulated by a number of intracellular molecules, including ATP, ADP, and membrane phosphoinositides, properties that enable them to couple metabolic changes to changes in cell exitability. KATP channels are formed by two distinct protein subunits: a sulfonylurea receptor (SUR.x) and an inwardly rectifying potassium channel subunity (Kir6.x). Using site-directed mutagenesis combined with patch-clamp recordings and biochemical experiments, we are investigating the molecular basis underlying channel regulation. Mutations in both SUR1 and Kir6.2 genes have been found in patients with insulin secretion diseases. To understand howthese mutations cause deregulation of insulin secretion, we are identifying the molecular defects of these mutant channels, in terms of their assembly, trafficking, and functional properties.

Many chemicals encountered in work places target ion channels to exert their toxic effects. Our efforts in understanding how ion channels function and interact with foreign substances at the molecular level will help us develop preventive strategies to block the effects of hazardous materials.

Yan FF, Casey J., Shyng SL. (2006) Sulfonylureas correct trafficking defects of disease-causing ATP-sensitive potassium channels by binding to the channel complex. J Biol Chem. Sep 6; Epub ahead of print. Abstract

Lin CW, Lin YW, Yan FF, Casey J, Kochhar M, Pratt EB, Shyng SL. (2006) Kir6.2 Mutations Associated With Neonatal Diabetes Reduce Expression of ATP-Sensitive K+ channels: Implications in Disease Mechanism and Sulfonylurea Therapy. Diabetes. Jun;55(6):1738-46. Abstract

Lin YW, MacMullen C, Ganguly A, Stanley CA, Shyng SL (2006). A novel KCNJ11 mutation associated with congenital hyperinsulinism reduces the intrinsic open probability of beta-cell ATP-sensitive potassium channels. J Biol Chem. Feb 3;281(5):3006-12. Abstract

Lin, C.-W., F. Yan, S. Shimamura, S. Barg, and S.-L. Shyng (2005). Membrane phosphoinositides control insulin secretion through their effects on ATP-sensitive K+ channel activity. Diabetes. Oct 54(10):2852-8. Abstract

Yan FF, Lin CW, Cartier EA, Shyng SL (2005). Role of ubiquitin-proteasome degradation pathway in biogenesis efficiency of b-cell ATP-sensitive potassium channels. Am J Physiol Cell Physiol. Nov 289(5):C1351-9. **Selected as Editorial Focus article. Abstract

Yan, F., C.-W. Lin, E. Weisiger, E. A. Cartier, G. Taschenberger, and S.-L. Shyng (2004). Sulfonylureas correct trafficking defects of ATP-sensitive potassium channels caused by mutations in the sulfonylurea receptor. J Biol Chem. Mar 19;279(12):11096-105. Abstract

Magge SN, Shyng SL, MacMullen C, Steinkrauss L, Ganguly A, Katz LE, Stanley CA (2004). Familial Leucine-Sensitive Hypoglycemia of Infancy Due to a Dominant Mutation of the beta-Cell Sulfonylurea Receptor. J Clin Endocrinol Metab. Sep;89(9):4450-4456. Abstract

Y.-W. Lin, T. Jia, A. Weinsoft, and S.-L. Shyng (2003). Stabilization of the activity of ATP-sensitive potassium channels by ion pairs formed between adjacent Kir6.2 subunits. J. Gen. Physiol., 122: 225-37. Abstract

Cartier, E. A., S. Shen, and S.-L. Shyng. (2003). Modulation of the Trafficking Efficiency and Functional Properties of ATP-sensitive Potassium Channels through a Single Amino Acid in the Sulfonylurea Receptor. J. Biol. Chem., 278: 7081-7090. Abstract

Huopio, H., S.-L. Shyng, T. Otonkoski, and C. G. Nichols. (2002). KATP channels and insulin secretion disorders. Am. J. Physiol. Endocrinol. Metab., invited review, 283: E207-E216. Abstract

Taschenberger, G., Mougey, A., Shen, S., Lester, L., LaFranchi, S., and Shyng, S.-L. (2002) Identification of a familial hyperinsulinism-causing mutation in the sulfonylurea receptor 1 that prevents normal trafficking and function of KATP channels. Journal of Biological Chemistry, 277:17139-17146. Abstract

Conti, L.R., Radeke, C.M., Shyng, S.-L., and Vandenberg, C.A. (2001) Transmembrane topology of the SUR1. Journal of Biological Chemistry 276, 41270-41278. Abstract

Cartier, E., Conti, L.R., Vandenberg, C.A., and Shyng, S.-L. (2001) Defective Trafficking and function of KATP channels caused by a sulfonylurea receptor 1 mutation associated with persistent hyperinsulinemic hypoglycemia of infancy. Proceedings of the National Academy of Sciences, U.S.A. 98, 2882-2887. Abstract

Shyng, S.-L., Cukras, C., Harwood, J., and Nichols, C.G. (2000) Structural determinants of PIP2 regulation of inward rectifier KATP channels. Journal of General Physiology 116,599-608. Abstract

A complete list of publications (PubMed)