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Ch'ng Toh Hean

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Assistant Professor Ch’ng Toh Hean
PhD
Nanyang Assistant Professor
Principal Investigator, Neurobiology of Long Term Memory Formation Laboratory




Team

  • Lim Wei Lee, Research Assistant
  • Chin Pei Wern, Research Assistant
  • Lim Fang Yi Agnes, PhD Student
  • Lee Yan Jun, PhD Student
  • Soon Hui Rong, PhD Student​


Introduction

Ch’ng Toh Hean is an Assistant Professor at Lee Kong Chian School of Medicine, Nanyang Technological University (NTU), Singapore. He is also jointly appointed in the School of Biological Sciences at NTU. Asst Prof Ch’ng was awarded the Nanyang Assistant Professorship in 2014.

Asst Prof Ch’ng obtained his Bachelor of Science degree in Biology and Minor in Biochemistry from Davidson College, a liberal arts college in North Carolina, where he studied flagellar proteins in Chlamydomonas reinhardtii. He then completed his PhD research at Princeton University, New Jersey, in the laboratory of Dr Lynn Enquist, studying the molecular mechanism of transneuronal spread of alphaherpesvirus in the nervous system. After leaving Princeton University, Asst Prof Ch’ng pursued his postdoctoral research and was later promoted to a research fellow in the laboratory of Dr Kelsey Martin at University of California, Los Angeles, studying the molecular mechanisms of long term memory storage in the brain. In the lab, Asst Prof Ch’ng focused his research on a potent transcriptional coactivator known as CRTC1, and showed that this coactivator undergoes activity-dependent translocation from the synapse to the nucleus and that it plays a crucial role in transcription-dependent neuronal plasticity.

Asst Prof Ch’ng’s work was partially funded by the NARSAD Young Investigator Research Fellowship and his research has thus far been recognised by the Parvin Foundation Award as well as the MBI Excellence in Research Award.


Research Focus

The human brain is comprised of billions of neurons that form a highly interconnected circuit capable of receiving, processing and responding to a range of stimuli. As neuronal networks rewire with experience, these synaptic connections also undergo persistent experience-dependent changes over time.  This constant strengthening and weakening of synapses in response to neuronal activity is known as synaptic plasticity and the long lasting forms of synaptic plasticity are the neurobiological foundations of learning and memory.

Asst Prof Ch'ng's cellular and molecular neurobiology laboratory is interested in elucidating the fundamental biology of how long-term memories are encoded. They believe that understanding the basic principles of memory formation is crucial for the development of effective and targeted therapies for any neurological disorder where patients suffer from memory loss or cognitive impairment.

The laboratory employs a multidisciplinary approach using different neuronal preparations to study signalling pathways and cellular event when neurons are activated during learning and memory. The techniques we use range from basic cell biology assays, protein biochemistry, live imaging to next generation sequencing technologies to study how neurons receive, relay and respond to incoming signals required to initiate a transcriptional response during experience-dependent rewiring of neuronal connections.

Synapse to nucleus signalling during transcription-dependent plasticity
The lab is focused on understanding how soluble signals associated with long-lasting forms of neuronal plasticity are relayed to the nucleus to alter gene expression. We are working to identify and expand the catalogue of synaptic proteins that undergo nuclear translocation as well as explore the kinetics and dynamics of this long-distance transport. In the context of neuronal plasticity, we want to identify what type of stimulus trigger synapse to nucleus signalling and how these proteins subsequently regulate changes in gene expression critical for long-term plasticity.

Nuclear plasticity during encoding of long-term memories
Synaptic signals that arrive at the nucleus can initiate a complex and robust response from the nucleus which includes modifications in the epigenome, transcriptome and composition of the proteome. We are interested in understanding how neuronal nuclei respond to activity-dependent changes in the context of memory formation and how these persistent alterations allow neurons to   encode memories. Ultimately, we hope to get a comprehensive and dynamic snapshot of various nuclear processes critical for establishing a memory engram. As a logical extension of this work, we want to understand how nuclear plasticity is impacted in diseased neurons and how that relates to memory loss.

Neuron-astrocyte metabolism during long-term plasticity
Neurons require a tremendous of energy during learning and memory and the interaction between neurons and astrocytes is critic​al to maintain this function. We are interested in understanding how the neuron-astrocyte relationship impacts learning and memory and how the transcriptional response in astrocytes and neurons helps to regulate the metabolic pathways required for proper neuronal function. We also want to understand how metabolic imbalance or disease can impact brain function particularly during memory formation.

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Selected Publications

Lim WL, Lim FY & Ch’ng TH (2016). Synapse to nucleus signalling and transcription-dependent plasticity. Learning & Memory, S1074-7427(16) 30124-1.

Ch’ng TH, DeSalvo MD, Lin P, Martin KC. (2015). Molecular mechanism of CRTC1 long distance signal transduction in neurons. Frontiers in Molecular Neuroscience, 8(48):1-19.


Ch’ng TH & Martin KC (2011). Synapse-to-nucleus signaling. Current Opinion in Neurobiology, 21(2):345-352.

Kratchamarov R, Kramer T, ..., Ch’ng TH, et al. (2013). Glycoprotein gE and gI are required for efficient KIF1A-dependent anterograde axonal transport of alphaherpesvirus particles in neurons. Journal of Virology, 87(17):9431-9440. 

Jeffrey RA, Ch’ng TH, O’Dell TJ, et al. (2009). Activity-dependent anchoring of importin alpha at the synapse involves regulated binding to the cytoplasmic tail of the NR1-1a subunit of the NMDA receptor. The Journal of Neuroscience, 29(50):15613-15620.

On KO, Zhao Y, Ch’ng TH, et al. (2008). Importin-mediated retrograde transport of CREB2/ATF4 from distal processes to the nucleus in neurons. Proceedings of the National Academy of Science of the United States of America, 105(44):17175-17180.

Dzudzor B, Huynh L, ..., Ch’ng TH, et al. (2010). Regulated expression of the Ras effector Rin1 in forebrain neurons. Molecular & Cellular Neuroscience, 43(1):108-116. 

Ch’ng TH & Enquist LW (2005). Neuron-to-cell spread of Pseudorabies Virus in a Compartmented Neuronal Culture System. Journal of Virology, 79(17):10875-10889. 


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