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Assistant Professor , Department of Physiology, National University of Singapore
Neuroregeneration in the developing and adult central nervous system (CNS)
The lab is interested in neurogenesis in the developing and adult brains and how resident stem cells or implanted stem cells can be used for cell replacement therapy in neurological disease.
Nutrition in brain development and neurodevelopmental disorders (Macrocephaly and Rett Syndrome)Neurogenesis in the process of generating neurons from neural stem cells and progenitor cells, and is most active in in the developing brain for proper brain formation and cognitive functions. My lab is interested to understand how nutrition, given during early post-natal period, can influence neurogenesis and subsequent cognitive functions. This understanding will help us to enhance brain development as well as neuronal and brain functions. In addition, we are exploring the possibilities of using nutrition as a therapeutic measure for neurodevelopmental disorders, specifically macrocephaly and Rett syndrome that show defects in neurogenesis and neuronal development respectively. Both macrocephaly and Rett syndrome are associated to Autism Spectrum Disorder (ASD), but have been shown to have strong contributions from genetic alterations. We are using zebrafish and mouse models as well as patients-derived stem cells to model both disorders in culture and in vivo, and to understand how our genes-of-interest are involved in the neuronal development and the associated cognitive defects in these disorders.
Adult NeurogenesisIn adult mammalian brains, neurogenesis occurs only in discrete regions. New neurons exist in the adult brains of many different species, and are continuously generated and integrated into the existing circuitry. Therefore, we are interested in dissecting the molecular mechanisms regulating the development and integration of these adult-born neurons including differentiation, growth, migration, path-finding and synapse formation. Specifically, we are studying how axon guidance cues and chloride channels are involved in adult neurogenesis.
Endogenous stem cells and implanted stem cells for cell replacement therapyAn understanding of the developmental processes of the newly generated neurons is not only important for deciphering the mystery in the adult brain, but also paving the way for cell replacement therapy. Stem cells transplanted into the adult brain can then be effectively accustomed for different brain disorders. Rodent disease models and cells from human patients (Parkinson’s disease and Rett Syndrome) are used in the lab to study and understand the mechanisms and the progression of the diseases, and also to explore neuroregeneration of the adult brain with exogenous or resident stem /progenitor cells.
The nutrition related work is funded by Abbott Nutrition, the axon guidance work is funded by GlaxoSmithKline (GSK) and the stem cell implantation in PD work is funded by National Research Foundation (NRF) – Competitive Research Programme (CRP).
Zhao N, Ma DL WY Leong, Han J, Van Dongen AMJ, Chen T and Goh EL (2015) Methyl-CpG-binding domain (MBD) is crucial for MeCP2 dysfunction-induced defects in adult newborn neurons. Frontiers in Cellular Neuroscience, in press
Ma DL, Yoon S, Yang C, Marcy G, Zhao N, Leong WY, Ganapathy V, Han J, Van Dongen AMJ, Ming G-L, Hsu K, Augustine GJ and Goh EL (2015) Rescue of MeCP2 dysfunction-induced defects in newborn neurons by modulating GABA signaling. Neurotherapeutics, 10.1007/s13311-015-0343-0
Su CT, Yoon S, Marcy G, Augustine GJ and Goh EL (2015) An optogenetic approach for assessing formation of neuronal connections in a co-culture system. J. Vis. Exp. (96), e52408, doi:10.3791/52408
Tan KK, Tann JY, Sathe S, Goh SH, Ma DL, Goh EL, Yim EK (2015) Enhanced Differentiation of Neural Progenitor Cells into Neurons of the Mesencephalic Dopaminergic Subtype on Topographical Patterns. Biomaterials. 43: 32-43
Nguyen NL, Ma DL, Shui GH, Wong PY, Zhang XD, Wenk MR, Goh EL and Silver DL (2014) Major Facilitator Superfamily Domain 2a (Mfsd2a) is required for normal uptake of docosahexaenoic acid in neuronal tissue. Nature, 509: 503-06.
Ng T, Ryu JR, Sohn JH, Tan T, Ming G-L, Song H and Goh EL (2013). Cdk5 and FAK-dependent regulation of dendritic outgrowth by class 3 Semaphorins. PLoS ONE, 8(6): e65572.
Oruganty Das A, Ng T, Udagawa T, Goh EL and Richter JD (2012) Translational control of mitochondrial energy production mediates neuron morphogenesis. Cell Metabolism, 16(6): 789-800.
Shivaraj MC, Marcy GT, Low GL, Ryu JR, Zhao X, Rosales F and Goh EL (2012) Effects of Taurine on neuronal development in the developing brains. PLoS ONE, 7(8): e42935.
Goh EL, Kim JY, Kuwako K, Tessier-Lavigne M, He Z, Griffin JW, Ming GL. Beta1-integrin mediates myelin-associated glycoprotein signaling in neuronal growth cones. Mol Brain. 2008 1, 10.
Ge S*, Goh, EL*, Sailor K, Kitabatake Y, Ming, GL, and Song H (2006) GABA regulates synaptic integration of newly generated neurons in the adult brain. * equal contribution authors. Nature 439,589-93.
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