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Calcium Signalling Laboratory


Principal Investigator and Head, Calcium Signalling Laboratory, NNI
Neuroscience Academic Clinical Program, SingHealth-Duke NUS
Associate Professor (0.4FTE), Singapore Institute of Technology
Associate Professor (Track IIA-research), Duke-NUS Graduate Medical School
Ph.D. National University of Singapore, 2001
Bachelor of Medicine, Master of Surgery (Neurosurgery)
West China University of Medical Sciences, Sichuan, China, 1996

Contact Information

Calcium Signalling Laboratory, Level 6, Lab 6
National Neuroscience Institute
11 Jalan Tan Tock Seng, Singapore 308433
Tel: (65) 6357 7611 (Office) / (65) 6357 7615 (Laboratory)
Fax:(65) 6256 9178

The Team

  • Dr Chen Bo
  • Dr Charlene Priscilla Poore
  • Dr Wei Shunhui
  • Ms Jeslyn Tan Si Qi
  • Dr Gayathri Rajamanickam


Cellular ionic homeostasis is a dynamic state regulating ions such as calcium, sodium, and potassium both within the cell and across the cell membrane. As ions determine major brain functions such as firing of action potential, disruption of its homoeostasis worsens tissue damage in diseases of central nervous system such as stroke and head injury. The research in our lab is focused on ion channels and transporters that are key to the disruption of ionic homeostasis in brain disorders. We aim to develop novel treatments to correct the ionic imbalance and translate them into clinical practice which will benefit patients.

One example is Transient receptor potential melastatin member 4 (TRPM4) which is upregulated after stroke. We have shown that TRPM4 inhibition could reduce cerebral edema, a major side effect after reperfusion treatment. A TRPM4 specific antibody M4P was thus developed in our lab to bind to and block the channel from extracellular space. We demonstrate that M4P could inhibit TRPM4 currents and subsequent cell swelling after hypoxia. In animal model of stroke, M4P was shown to protect vasculature after stroke reperfusion and potentially extend the time window of reperfusion therapy. M4P also exhibits the potential to benefit patients suffered from other brain disorders.  We welcome collaborations from industry partners and philanthropic donation to co-develop the antibody and accelerate its translational process.

Figure 1.

Figure 1. TRPM4 inhibition protects blood-brain barrier after stroke reperfusion. (A) Exemplar images of T2WI and PET obtained from rats 24 hours post stroke reperfusion. Brain swelling was manifested as the midlines being shifted to the opposite hemisphere (arrows). TRPM4 inhibition by siRNA significantly reduces cerebral edema and infarct formation. (B) Schematic representation of TRPM4 channel with the antigenic epitope for M4P labelled in red. (C) Cell swelling, exhibited as membrane capacitance Cm, was induced by hypoxia in control IgG treated cells. M4P treatment significantly ameliorates cell swelling. No difference was observed between M4P and control normoxia. (D) Quantification of Evans blue extravasation demonstrates that M4P protects vasculature during reperfusion therapy.

About Stroke

Stroke is a leading cause of death and disability worldwide. This medical emergency occurs when blood flow to an area of the brain is cut off. There are two types of stroke, ischemic and hemorrhagic. About 80 percent of strokes are ischemic strokes, caused by the blockage of a cerebral blood vessel.

The goals of treatment of acute ischemic stroke are to restore blood flow. Currently, the only FDA-approved treatment for ischemic strokes is tissue plasminogen activator (tPA) which must be given to eligible patients within a short time window (<4.5 hours after stroke onset). Patients with tPA treatment have a much better outcome.  The earlier the treatment, the better the result. Recanalisation beyond this time window may generate severe side effects such as malignant edema and hemorrhage due to vascular injury which can be potentially treated with our TRPM4 blocking antibody.

As time is critical for stroke treatment, recognizing the signs of a stroke can save a life. Use the letters in "FAST" to spot stroke signs and know when to call ambulance: Face drooping, Arm weakness, Speech difficulty, Time to call 995 (Singapore).

Selected Publications (* joint first author, † corresponding author)

  1. Ahad MA, Chear NJ, Abdullah MH, Ching-Ga TAF, Liao P † , Wei S, Murugaiyah V, Hassan Z † . Effects of clitorienolactones from Clitoria ternatea root on calcium channel mediating hippocampal long-term potentiation in rats induced chronic cerebral hypoperfusion. Ageing Res Rev. 2024 Mar 3;96:102252.

  2. Poore CP, Wei S, Chen B, Low SW, Tan JSQ, Lee AT, Nilius B, Liao P † . In vivo evaluation of monoclonal antibody M4M using a humanised rat model of stroke demonstrates attenuation of reperfusion injury via blocking human TRPM4 channel. J Drug Target. 2024 Feb 12:1-10.

  3. Poore CP, Hazalin NAMN, Wei S, Low SW, Chen B, Nilius B, Hassan Z, Liao P † . TRPM4 blocking antibody reduces neuronal excitotoxicity by specifically inhibiting glutamate-induced calcium influx under chronic hypoxia. Neurobiol Dis. 2024 Feb;191:106408.

  4. Wei S, Chen B, Low SW, Poore CP, Gao Y, Nilius B, Liao P † . SLC26A11 Inhibition Reduces Oncotic Neuronal Death and Attenuates Stroke Reperfusion Injury. Mol Neurobiol. 2023 Oct;60(10):5931-5943.

  5. Chen B, Wei S, Low SW, Poore CP, Lee AT, Nilius B, Liao P†. TRPM4 Blocking Antibody Protects Cerebral Vasculature in Delayed Stroke Reperfusion. Biomedicines. 2023 May 19;11(5):1480.
  6. Gu L, Liao P†, Liu H. Cancer-associated fibroblasts in acute leukemia. Front Oncol. 2022 Dec 19;12:1022979.
  7. Wei S, Behn J, Poore CP, Low SW, Nilius B, Fan H, Liao P†. Binding epitope for recognition of human TRPM4 channel by monoclonal antibody M4M. Sci Rep. 2022 Nov 15;12(1):19562.
  8. Low SW, Gao Y, Wei S, Chen B, Nilius B, Liao P † . Development and characterization of a monoclonal antibody blocking human TRPM4 channel. Sci Rep. 2021 May 17;11(1):10411.
  9. Wei S, Low SW, Poore CP, Chen B, Gao Y, Nilius B, Liao P † . Comparison of Anti-oncotic Effect of TRPM4 Blocking Antibody in Neuron, Astrocyte and Vascular Endothelial Cell Under Hypoxia. Front Cell Dev Biol. 2020 Oct 19;8:562584.
  10. Hazalin NAMN, Liao P†, Hassan Z†. TRPM4 inhibition improves spatial memory impairment and hippocampal long-term potentiation deficit in chronic cerebral hypoperfused rats. Behav Brain Res. 2020 Jun 30:112781.
  11. Ahad MA, Kumaran KR, Ning T, Mansor NI, Effendy MA, Damodaran T, Lingam K, Wahab HA, Nordin N, Liao P, Müller CP, Hassan Z Insights into the neuropathology of cerebral ischemia and its mechanisms. Rev Neurosci. 2020 Mar 3
  12. Alkaff SA, Radhakrishnan K, Nedumaran AM, Liao P, Czarny B. Nanocarriers for Stroke Therapy: Advances and Obstacles in Translating Animal Studies. Int J Nanomedicine. 2020 Jan 21;15:445-464.
  13. Chen B, Gao Y, Wei S, Low SW, Ng G, Yu D, Tu TM, Soong TW, Nilius B, Liao P†. TRPM4-specific blocking antibody attenuates reperfusion injury in a rat model of stroke. Pflugers Arch. 2019 Dec;471(11-12):1455-1466.
  14. Zhang E, Liao P†. Brain-derived neurotrophic factor and post-stroke depression. J Neurosci Res. 2020 Mar;98(3):537-548.
  15. Gao Y, Liao P†. TRPM4 channel and cancer. Cancer Lett. 2019 Jul 10;454:66-69.
  16. Loh KY, Wang Z, Liao P†. Oncotic Cell Death in Stroke. Rev Physiol Biochem Pharmacol. 2019;176:37-64.
  17. Chen B, Ng G, Gao Y, Low SW, Sandanaraj E, Ramasamy B, Sekar S, Bhakoo K, Soong TW, Nilius B, Tang C, Robins EG, Goggi J, Liao P†. Non-Invasive Multimodality Imaging Directly Shows TRPM4 Inhibition Ameliorates Stroke Reperfusion Injury. Transl Stroke Res. 2019 Feb; 10(1):91-103.
  18. Hu Z, Li G, Wang JW, Chong SY, Yu D, Wang X, Soon JL, Liang MC, Wong YP, Huang N, Colecraft HM, Liao P, Soong TW. Regulation of Blood Pressure by Targeting CaV1.2-Galectin-1 Protein Interaction. Circulation. 2018 Oct 2;138(14):1431-1445.
  19. Damodaran T, Tan BWL, Liao P, Ramanathan S, Lim GK, Hassan Z. Clitoria ternatea L. root extract ameliorated the cognitive and hippocampal long-term potentiation deficits induced by chronic cerebral hypoperfusion in the rat. J Ethnopharmacol. 2018 Jun 18;224:381-390.
  20. Wang J, Li G, Yu D, Wong YP, Yong TF, Liang MC, Liao P, Foo R, Hoppe UC, Soong TW. Characterization of CaV1.2 exon 33 heterozygous knockout mice and negative correlation between Rbfox1 and CaV1.2 exon 33 expressions in human heart failure. Channels (Austin). 2018 Jan 1;12(1):51-57.
  21. Li G, Wang J, Liao P, Bartels P, Zhang H, Yu D, Liang MC, Poh KK, Yu CY, Jiang F, Yong TF, Wong YP, Hu Z, Huang H, Zhang G, Galupo MJ, Bian JS, Ponniah S, Trasti SL, See K, Foo R, Hoppe UC, Herzig S, Soong TW. Exclusion of alternative exon 33 of CaV1.2 calcium channels in heart is proarrhythmogenic. Proc Natl Acad Sci U S A. 2017 May 23;114(21):E4288-E4295.
  22. Hu Z, Wang JW, Yu D, Soon JL, de Kleijn DP, Foo R, Liao P, Colecraft HM, Soong TW. Aberrant Splicing Promotes Proteasomal Degradation of L-type CaV1.2 Calcium Channels by Competitive Binding for CaVβ Subunits in Cardiac Hypertrophy. Sci Rep. 2016 Oct 12;6:35247.
  23. Qiu L, Ng G, Tan EK, Liao P†, Kandiah N†, Zeng L†. Chronic cerebral hypoperfusion enhances Tau hyperphosphorylation and reduces autophagy in Alzheimer's disease mice. Sci Rep. 2016 Apr 6;6:23964.
  24. 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. Genetic Interactions Between TRPC6 and NPHS1 Variants Affect Posttransplant Risk of Recurrent Focal Segmental Glomerulosclerosis. Am J Transplant. 2015 Dec;15(12):3229-38.
    A commentary on this work was published in Nat Rev Nephrol: Edwards JK. Glomerular disease: TRPC6 and NPHS1 mediate FSGS risk. 2015 Sep; 11(9):505
  25. 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.
  26. Zhang E, Liao P†. Brain transient receptor potential channels and stroke. J Neurosci Res. 2015 Aug;93(8):1165-83.
    Featured article as an Editor’s choice for the August issue of the Journal of Neuroscience Research.
  27. Damodaran T, Hassan Z, Navaratnam V, Muzaimi M, Ng G, Müller CP, Liao P, Dringenberg HC. Time course of motor and cognitive functions after chronic cerebral ischemia in rats. Behav Brain Res.
     2014 Dec 15;275:252-8.
  28. Sharma P, Liao P. Calcium ion Influx in Microglial Cells: Physiological and Therapeutic Significance.
    J Neurosci Res. 2014 Apr;92(4):409-23.
  29. Loh KP, Ng G, Yu CY, Fhu CK, Yu D, Vennekens R, Nilius B, Soong TW, Liao P†. TRPM4 inhibition promotes angiogenesis after ischemic stroke. European Journal of Physiology (Pflugers Arch).
     2014 Mar;466(3):563-76.
  30. Yu CY, Ng G, Liao P†. Therapeutic Antibodies in Stroke. Transl Stroke Res. 2013;4:477-483.
  31. Papanayotou C*, De Almeida I*, Liao P*, Oliveira NM, Lu SQ, Kougioumtzidou E, Zhu L, Shaw A, Sheng G, Streit A, Yu D, Wah Soong T, Stern CD. Calfacilitin is a calcium channel modulator essential for initiation of neural plate development. Nat Commun. 2013;4:1837.
  32. 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.
  33. Zhang HY*, Liao P*, Yu D, Soong TW. Alternative splicing of Cav1.2 channels determines the diltiazem sensitivity between cardiac and smooth muscle. British Journal of Pharmacology.
     2010 Aug;160(7):1631-40.
  34. Liao P†, Soong TW. Cav1.2 channelopathies: from arrhythmias to autism, bipolar disorder, and immunodeficiency. European Journal of Physiology (Pflugers Arch). 2010 Jul;460(2):353-9.
    This paper is one of the most frequently downloaded articles of this journal in 2010.
  35. Liao P, Li G, Yu D, Yong TF, Wang J, Soong TW. Molecular alteration of Cav1.2 calcium channel in chronic myocardial infarction. European Journal of Physiology (Pflugers Arch). 2009 Aug;458(4):701-11.
  36. Liao P, Zhang HY, Soong TW. Alternative splicing of voltage-gated calcium channels: from molecular biology to disease. European Journal of Physiology (Pflugers Arch). 2009 Jul;458(3):481-7.
  37. Tao J, Hildebrand ME, Liao P, Liang MC, Tan G, Li S, Snutch TP, Soong TW. Activation of corticotropin-releasing factor receptor 1 selectively inhibits Cav3.2 T-type calcium channels. Mol Pharmacol. 2008 Jun;73(6):1596-609.
  38. Tang ZZ, Liao P, Li G, Jiang FL, Yu D, Hong X, Yong TF, Tan G, Lu S, Wang J, Soong TW. Differential Splicing Patterns of L-Type Calcium Channel Cav1.2 Subunit in Hearts of Spontaneously Hypertensive Rats and Wistar Kyoto Rats. Biochim Biophys Acta.-MOL CELL RES. 2008 Jan;1783(1):118-30.
  39. Liao P, Yu D, Li G, Yong TF, Soon JL, Chua YL, Soong TW. A smooth muscle Cav1.2 calcium channel splice variant underlies hyperpolarized window current and enhanced state-dependent inhibition by nifedipine. J Biol Chem. 2007 Nov 30;282(48):35133-42.
  40. Shen Y, Yu D, Hiel H, Liao P, Yue DT, Fuchs PA, Soong TW. Alternative splicing of the Cav1.3 channel IQ domain, a molecular switch for Ca2+-dependent inactivation within auditory hair cells. J Neurosci. 2006 Oct 18;26(42):10690-9.
  41. Liao P, Yong TF, Liang MC, Yue DT, Soong TW. Splicing for alternative structures of Cav1.2 Ca2+ channels in cardiac and smooth muscles. Cardiovasc Res. 2005 Nov 1;68(2):197-203.
  42. Liao P, Yu D, Lu S, Tang ZZ, Liang MC, Zeng S, Lin W, Soong TW. Smooth muscle selective alternatively spliced exon generates functional variation in Cav1.2 calcium channels. J Biol Chem. 2004 Nov 26;279(48):50329-35.

Achievements of Students

  1. Dr Loh Kep Yong (Duke-NUS Medical School):
    • Silver Medal, NNRIS Research Day, 2018
    • $10K Research Grant from Duke-NUS Medical School
    • Oral Presentation in 4th Congress of the European Academy of Neurology, Lisbon, Portugal, June 2018
    • AM-ETHOS Learning Enhancement And Progress (LEAP) Award, 2019
    • Most Outstanding Best Science Research Thesis, Duke-NUS Medical School, 2019
  2. Lee Rui Zhi (Duke-NUS Medical School):
    • Best Poster Presentation Award, Research Day, Duke-NUS Medical School, 2017
  3. Quek Hui Lin Jamie and Eong Rui Xuan (Ngee Ann Polytechnic, 2014):
    • First Prize (Distinction Award), The Young Scientists' Symposium
    • Winning Team, Polytechnic Student Research Programme
  4. Byorn Tan (NUS High School of Mathematics and Science, 2013)
    • Second Award, Taiwan International Science Fair
  5. Jin Chentian (Raffles Institution, 2012):
    • Silver Medal, Singapore Science and Engineering Fair
    • Second Prize, A*STAR Talent Search