Prof Soong Tuck Wah
Distinguished Visiting Scientist, National Neuroscience InstituteHead and Professor, Department of PhysiologySenior Faulty, NUS Graduate School for Engineering and Integrative SciencesGroup Leader, Neurobiology/Ageing ProgrammeOverall Coordinator, Singapore Graduate Programme in Neuroscience, NGSPast President and founding member of the SfN Singapore Chapter
Department of PhysiologyYong Loo Lin School of medicineNational University of SingaporeNeurobiology/Ageing ProgrammeCentre for Life Sciences28 Medical Drive #04-07 Singapore 117456Tel: (65) 6516 1938 Email: email@example.com
Overview of Laboratory
Ion Channels and Transporters LaboratoryIon 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.
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