Dr. Shieh, Ru-Chi

Research Fellow

  • Biophysics/Electrophysics
  • Fluorescence/Ion Chennel
  • Thermodynamics

Education and Positions:
  • Ph.D. University of Rochester

Ion channels are membrane proteins that control specific ions moving across cells. Ion movement across the cell membrane results in membrane potential changes, which are used as rapid and accurate signals in organisms. Outward currents through inward rectifier K+ channels (Kir) are important in maintaining stable resting membrane potentials, controlling excitability, and thus regulating physiological processes such as vascular tone, heart rate, renal salt flow, and insulin release.  Outward Kir currents increase as [K+]o increases and that elevated outward Kir currents are related to patho-physiological states such as in ischemia, tachycardia, and fibrillation, but the underlying mechanism remains a mystery. We have characterized how outward Kir single-channel currents and their kinetics are modulated by extracellular cations and intracellular polyamines. We are investigating how these regulations of outward Kir currents can be applicable to treatment of arrhythmia. In addition, we use Linkage Analysis based on thermodynamics to characterize and quantitate allosteric interaction of various domains in ion channels. Finally, we are developing photo-activated potassium- and calcium-selective ion channels. After both channel types are constructed, we can switch on and off cell excitability (electrical signals) via optical signals in the brain and heart, thereby allowing us to control functions and understand cell networking in these two types of cells. We anticipate the results of these studies will lead to new research tools and novel therapy interventions for a number of diseases including epilepsy in the brain as well as heart failure and arrhythmia in the heart.

Our Team
Team photo

Journal 23 Book 0

  1. Sigg DM, Chang HK, Shieh RC Linkage analysis reveals allosteric coupling in Kir2.1 channels. The Journal of general physiology 150(11), 1541-1553 (2018) [JCR] [WOS]
  2. Liu CH, Chang HK, Lee SP, Shieh RC Activation of the Ca2+-sensing receptors increases currents through inward rectifier K+ channels via activation of phosphatidylinositol 4-kinase. Pflugers Archiv : European journal of physiology 468(11-12), 1931-1943 (2016) [JCR] [WOS]
  3. Chang HK, Iwamoto M, Oiki S, Shieh RC Mechanism for attenuated outward conductance induced by mutations in the cytoplasmic pore of Kir2.1 channels. Scientific reports 5, 18404 (2015) [JCR] [WOS]
  4. Hsueh-Kai Chang and Ru-Chi Shieh Voltage-dependent inhibition of Kir2.1 outward currents by extracellular spermine BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1828, 765-775 (2013-02) [JCR] [WOS]
  5. T-A Liu; H-K Chang; (R-C Shieh*) . Revisiting Inward Rectification: K Ions Permeate through Kir2.1 Channels during High-Affinity Block by Spermidine. JOURNAL OF GENERAL PHYSIOLOGY 139, 245-259 (2012-02) [JCR] [WOS]
  6. T-A Liu; H-K Chang; (R-C Shieh*) Extracellular K+ elevates outward currents through Kir2.1 channels by increasing single-channel conductance. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1808(6), 1772-1778 (2011-06) [JCR] [WOS]
  7. Hsueh-Kai Chang, Jay-Ron Lee, Tai-An Liu, Ching-Shu Suen, Jorge Arreola, and Ru-Chi Shieh* The extracellular K+ concentration-dependence of outward currents through Kir2.1 channels is regulated by extracellular Na+ and Ca2+. JOURNAL OF BIOLOGICAL CHEMISTRY 285(30), 23115-23125 (2010) [JCR] [WOS]
  8. Kun-Chi Chiang, Ling-Ping Lai, and *Ru-Chi Shieh** Characterization of a novel Nav1.5 channel mutation, A551T, associated with Brugada syndrome. JOURNAL OF BIOMEDICAL SCIENCE 16, 76 (2009) [JCR] [WOS]
  9. Hsueh-Kai Chang, Laurence J. Marton, Kuo Kan Liang, and *Ru-Chi Shieh K^+ binding in the G-loop and water cavity facilitates Ba^2+ movement in the Kir2.1 channel. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 1788, 500-506 (2009) [JCR] [WOS]
  10. Hsuan-Wen Hwang, Jay-Ron Lee, Kuan-Yu Chou, Ching-Shu Suen, Ming-Jing Hwang, Chinpan Chen, *Ru-Chi Shieh*, Lee-Young Chau** Oligomerization is crucial for the stability and function of heme oxygenase-1 in the endoplasmic reticulum. JOURNAL OF BIOLOGICAL CHEMISTRY 284(34), 22672-22679 (2009) [JCR] [WOS]