LIAO PING, MD, Ph.D.
Principal Investigator and Head, Calcium Signalling Laboratory, NNINeuroscience Academic Clinical Program, SingHealth-Duke NUSAssociate Professor (0.4FTE), Singapore Institute of TechnologyAssociate Professor (Track IIA-research), Duke-NUS Graduate Medical SchoolPh.D. National University of Singapore, 2001Bachelor of Medicine, Master of Surgery (Neurosurgery)West China University of Medical Sciences, Sichuan, China, 1996
Contact Information
Calcium Signalling Laboratory, Level 6, Lab 6National Neuroscience Institute11 Jalan Tan Tock Seng, Singapore 308433 Tel: (65) 6357 7611 (Office) / (65) 6357 7615 (Laboratory) Fax:(65) 6256 9178 Email: [email protected]
The Team
Overview
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)
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.
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.
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.
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.
Achievements of Students
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