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Ion Channel and Transport Laboratory

Prof Soong Tuck Wah

Current Appointment(s) 

Distinguished Visiting Scientist, National Neuroscience Institute
Head and Professor, Department of Physiology
Senior Faulty, NUS Graduate School for Engineering and Integrative Sciences
Group Leader, Neurobiology/Ageing Programme
Overall Coordinator, Singapore Graduate Programme in Neuroscience, NGS
Past President and founding member of the SfN Singapore Chapter 

Contact Information

Department of Physiology
Yong Loo Lin School of medicine
National University of Singapore
Neurobiology/Ageing Programme
Centre for Life Sciences
28 Medical Drive #04-07 Singapore 117456
Tel: (65) 6516 1938
Email: phsstw@nus.edu.sg

The Team

Research Fellows

  • Dr Katherine Chew
  • Dr Huang Ha
  • Dr Lin Qingshu
  • Dr Liu Chao
  • Dr Zhai Jing

Research Assistants

  • Liang Mui Cheng
  • Wong Yuk Peng

Laboratory Technicians

  • Yong Tan Fong (Lab Manager)
  • Yu Dejie

Overview of Laboratory

Ion Channels and Transporters Laboratory
Ion channels and transporters play essential roles in generating and maintaining electrical excitability of membranes found in neurons and muscle cells. The voltage-gated calcium channels support an equally role in Ca2+ signalling to initiate gene transcription or to activate Ca2+-dependent processes that have wider implications in cellular activities.

My laboratory have two major interests: (1) To investigate and understand the physiological significance of post-transcriptional modifications such as alternative splicing and RNA editing in diversifying calcium channel function in the nervous and cardiovascular systems; and to understand the underlying mechanisms relating to the dynamic changes in post-transcriptional modifications and channel functions and (2) To examine the role of iron transporter DMT1 and the interaction between activation of calcium channels and lysosomal biology in neurodegeneration and in Parkinson disease.

We have used the “Transcript-scanning” method to identify the comprehensive suite of alternatively spliced sites in calcium channels expressed in the CNS and CVS. The splice variants were functionally characterized by patch-clamp electrophysiology to display a spectrum of biophysical and pharmacological properties, and were shown to mediate splice-variant selective modulations by interacting proteins. To further examine their physiological importance, knock-out mouse technology was used to either selectively delete an alternative exon or to abolish the ability of the channel to undergo RNA editing. These mice exhibited phenotypes that lead us to further interrogate the role of the splice variants and RNA editing in human pathology or in animal models of disease. Notably our knock-out mice exhibited mood disorders, and altered learning and memory systems. Besides, late-LTP was altered in the hippocampus and spiking frequency reduced in the suprachiamatic nucleus. We are therefore interested to investigated more behavioural changes such as sleep-wake cycle, and also metabolic changes.

Our work on the DMT1 led us to investigate its divalent metal ion transport and the rescue of Mn2+ toxicity by competing Fe2+ influx. Our data showed robust nitrosylation of the DMT1 to enhance divalent ion entry and this has implications in neuronal degeneration and suggests a role of neuroinflammation in brain disorders. We have also investigated differential signalling between calcium channel splice variants and lysosomal function and its wider implications in neuronal survival. Recently we have widened our work on neuroinflammation to investigate the effects nitrosylation has on CaV1.2 channels in relation to ageing and Alzheimer’s disease.

Selected Publications

  1. Ryan DP, Dias da Silva MR, Soong TW, Fontaine B, Donaldson MR, Kung, AW, Jongjaroenprasert W, Liang MC, Khoo DH, Cheah JS, Ho SC, Bernstein HS, Maciel RM, Brown RH and Ptacek L. Mutations in a novel potassium channel (Kir2.6) causes susceptibility to thyrotoxic hypokalemic periodic paralysis. Cell. 2010 Jan 8; 140(1):88-98. (Faculty 1000/Biology)
  2. Xu JH, Long L, Wang J, Tang YC, Hu HT, Soong TW, Tang FR. Nuclear Localization of Ca (v) 2.2 and its Distribution in the Mouse Central Nervous System, and Changes in the Hippocampus during and after Pilocarpine-induced Status Epilepticus. Neuropathol Appl Neurobiol. 2010 Feb; 36(1):71-85.
  3. Liao P, Soong TW. Ca (V) 1.2 channelopathies: from arrhythmias to autism, bipolar disorder, and immunodeficiency. Pflugers Arch. 2010 Jul; 460(2):353-9; 2009 Nov 15. [Epub ahead of print]
  4. Zhang HY, Liao P, Yu D and Soong TW. Alternative splicing modulates diltiazem sensitivtity of cardiac and smooth muscle Cav1.2 calcium channels. BJP. (2010), 160, 1631–1640.
  5. Ang ET, Tai YK, Lo SQ, Seet R, Soong TW. Neurodegenerative diseases:exercising toward neurogenesis and neuroregeneration. Front Aging Neurosci.  2010 Jul 21, 2:25.
  6. Soon JL, Ping L, Chua YL, Soong TW, Sin KY. Absence of calcium channel alpha1C-subunit mutation in human atrial fibrillation. Asian Cardiovasc Thorac Ann. 2010 Aug;18(4):349-53.
  7. Liao P and Soong TW. Understanding alternative splicing of Cav 1.2 calcium channels for a new approach towards individualized medicine. Journal of Biomedical Research. Volume 24, Issue 3, May 2010, Pages 181-186.
  8. Chew KC, Ang ET, Tai YK, Tsang F, Lo SQ, Ong E, Ong WY, Shen HM, Lim KL, Dawson VL, Dawson TM, Soong TW. Enhanced Autophagy from Chronic Toxicity of Iron and Mutant A53T {alpha}-Synuclein: IMPLICATIONS FOR NEURONAL CELL DEATH IN PARKINSON DISEASE. J Biol Chem. 2011 Sep 23;286(38):33380-.
  9. Wang J, Thio SS, Yang SS, Yu D, Yu CY, Wong YP, Liao P, Li S, Soong TW. Splice Variant Specific Modulation of Cav1.2 Calcium Channel by Galectin-1 Regulates Arterial Constriction. Circ Res.  2011 Nov 11;109(11):1250-8.
  10. Wu ZY, Yu DJ, Soong TW, Dawe GS, Bian JS. Progesterone impairs human ether-a-go-go-related gene (HERG) trafficking by disruption of intracellular cholesterol homeostasis. J Biol Chem. 2011 Jun 24;286(25):22186-94.
  11. Tan BZ, Jiang F, Tan MY, Yu D, Huang H, Shen Y, Soong TW. Functional characterization of alternative splicing in the C-terminus of L-type CaV1.3 channels. J Biol Chem. 2011 Dec 9;286(49):42725-35. [Epub ahead of print]
  12. Tan GM, Yu D, Wang J and Soong TW. Alternative Splicing at C-terminus of CaV1.4 Calcium Channel Modulates Calcium Dependent Inactivation, Activation Potential and Current Density. J Biol Chem. 2012 Jan 6;287(2):832-47.
  13. H Huang, BZ Tan, Y Shen, J Tao, F Jiang, YY Sung, CK Ng, M Raida, G, Köhr, M Higuchi, H Fatemi-Shariatpanahi, DT Yue and TW Soong. RNA editing of the IQ domain in Cav1.3 channels modulates their Ca2+-dependent inactivation. Neuron, 2012 Jan 26;73(2):304-16. (Faculty 1000/Biology).
  14. Gan S-W, Tan E, Lin X, Yu D, Wang J, Tan GM, Vararattanavech A, Yeo CY, Soon CH, Soong TW, Pervushin K and Torres J. The Small Hydrophobic Protein Of The Human Respiratory Syncytial Virus Forms Pentameric Ion Channels. J Biol Chem. 2012 Jul 13;287(29):24671-89. Epub 2012 May 23.
  15. Navakkode S, Sajikumar S, Korte M and Soong TW. Dopamine induces LTP differentially in apical and basal dendrites through BDNF and voltage dependent calcium channels. Learn Mem.  2012 Jun 20;19(7):294-9.
  16. Klionsky DJ et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy.  2012 Apr;8(4):445-544.
  17. Papanayotou C, Almeida ID, Liao P, Oliveira NA, Lu SQ, Kougioumtzidou, E, Zhu L, Shaw A, Sheng G, Streit A, Yu D, Soong TW and Stern CD. Calfacilitin: a novel calcium channel modulator essential for initiation of neural plate development. Nature Commun 4, 1837, 14 May 2013.
  18. Huang H, Yu D and Soong TW. C-terminal post-transcriptional modification of CaV1.3 channels distinctively modulates their dihydropyridine sensitivity. Mol Pharmacol. 2013 Oct;84(4):643-53.
  19. Bazzazi H, Johny MB, Adams PJ, Soong TW and Yue DT. Continuosly tunable Ca2+ regulation of RNA-edited CaV1.3 channels. Cell Reports. 2013, Oct 31; 5:1-11. doi:10.1016/j.cell.rep2013.09.006.
  20. KP Loh, G Ng, CY Yu, CK F, RVennekens, B Nilius, TW Soong* and P Liao*. TRPM4 inhibition promotes angiogenesis after ischemic stroke. Pflugers Archive 2014, Mar; 466 (3): 563-76. *co-corresponding
  21. Huang H, Ng CY, Yu D, Zhai J, Lam Y and Soong TW. Modest CaV1.3V42-selective inhibition by compound 8 is β-subunit dependent. Nature Commun 2014, Jul 24; 5:4481. (Faculty 1000/Prime)
  22. Woon PS, Sum MY, Kuswanto CN, Yang GL, Sitoh YY, Soong TW, Lee TS, Nowinski, WL, Sim K. CACNA1C genomewide supported psychosis genetic variation affects cortical brain white matter integrity in Chinese patients with schizophrenia. J Clin Psychiatry 2014 Nov;75(11):e1284-90.
  23. Liao P, Yu D, Hu Z, Liang MC, Wang JJ, Yu CY, Ng G, Yong TF, Soon JL, Chua YL, Soong TW Alternative splicing generates a novel truncated Cav1.2 channel in neonatal rat heart. J Biol Chem 2015 Apr 3;290(14):9262-72, Feb 18.[Epub ahead of print]
  24. Kim YS, Kim YB, Kim WB, Yoon BE, Shen FY, Lee SW, Soong TW, Han HC, Colwell CS, Lee CJ, Kim YI. Histamine resets the circadian clock in the suprachiasmatic nucleus through the H1R-Ca(V) 1.3-RyR pathway in the mouse. Eur J Neurosci.
  25. Sun ZJ, Ng KH, Liao P, Zhang Y, Ng JL, Liu ID, Tan PH, Chong SS, Chan YH, Liu J, Davila S, Heng CK, Jordan SC, Soong TW*, Yap HK*. (*co-lead authors) Genetic Interactions Between TRPC6 and NPHS1 Variants Affect Posttransplant Risk of Recurrent Focal Segmental Glomerulosclerosis. Am J Transplant. 2015 Jul 3. doi: 10.1111/ajt.13378. [Epub ahead of print] PubMed PMID: 26147534.
  26. Soong TW, Mori MX. Post-transcriptional modifications and "Calmodulation" of voltage-gated calcium channel function: Reflections by two collaborators of David. T. Yue. Channels (Austin). 2015 Jun 8:0. [Epub ahead of print] PubMed PMID:26054929.​