Gong Chen

Neurodevelopment and Neurodegeneration

My lab employs multidisciplinary approaches, including molecular biology, fluorescence imaging, electrophysiology, immunocytochemistry, biochemistry, and electron microscopy to study the molecular mechanisms of brain development and neurodegenerative disorders. We currently are developing stem cell therapy for the treatment of neurological disordes.

How brain circuit is established and regulated to carry out complex functions is the most fascinating question in neuroscience research. Many neurological disorders are due to improper formation of neural circuits. My lab investigates the molecular and cellular mechanisms of synapse formation and synaptic plasticity, with a special focus on GABAergic synapse in the developing brain. GAGA signaling emerges very early during embryonic brain development. GABA function changes from excitation in immature neurons to inhibition in mature neurons. We previously have investigated GABAergic function during epileptogenesis and established a novel chemical-induced epilepsy model. Recently, we are studying GABAergic deficits in psychiatric disorders, including autism and schizophrenia. We also are starting to use stem cells, including induced pluripotent stem cells (iPSCs), to model neurological disorders and to study GABA regulation of stem cell development.

Neurodegenerative disorders afflict millions of people worldwide and have become an enormous socioeconomic burden for society. Our goal is to develop an effective therapy to reduce or alleviate the symptoms and help patients live an independent life. Our strategy is centered on synapses because synaptic loss is the first step leading to neurodegeneration. We are investigating the molecular mechanisms underlying synaptic loss during neurodegeneration, with an emphasis on synaptic deficits induced by cytoskeleton protein aggregation. We also are developing a neural stem cell therapy, including using iPSCs to treat neurodegenerative disorders.

Brennand, K., A. Simone, J. Jou, C. Gelboin-Burkhart, N. Tran, S. Sangar, Y. Li, Y. Mu, G. Chen, D. Yu, S. McCarthy, J. Sebat, and F. Gage. 2011. Modeling schizophrenia using human induced pluripotent stem cells. Nature 473: 221-225.

Sun, C., M.-C. Cheng, R. Qin, D.L. Liao, T.-T. Chen, F.-J. Koong, G. Chen, and C.-H. Chen. 2011. Identification and functional characterization of rare mutations of the neuroligin-2 gene (NLGN2) associated with schizophrenia. Human Molecular Genetics Published online May 6, 2011.

Fan, Y., X. Tang, E. Vitriol, G. Chen, and J. Q. Zheng. 2011. Actin capping protein is required for dendritic spine development and synapse formation. Journal of Neuroscience 31(28): 10228-10233.

Marchetto, M. C. N., C. Carromeu, A. Acab, D. Yu, G. Yeo, Y. Mu, G. Chen, F. H. Gage, and A. R. Muotri. 2010. A model for neural development and treatment of Rett Syndrome using human induced pluripotent stem cells. Cell 143: 527-539.

Gu, J., C. W. Lee, Y. Fan, D. Komlos, X. Tang, C. Sun, K. Yu, H. C. Hartzell, G. Chen, J. R. Bamburg, and J. Q. Zheng. 2010. ADF/cofilin-mediated actin dynamics regulate AMPA receptor trafficking during synaptic plasticity. Nature Neuroscience 13: 1208-1215.

Han, X. W., X. Wu, W. Y. Chung, T. Li, A. Nekrutenko, N. S. Altman, G. Chen, and H. Ma. 2009. Transcriptome of embryonic and neonatal mouse cortex by high-throughput RNA sequencing. Proc.Nat. Acad. Sci. USA 106: 12741-12746.

Jiang, M. and G. Chen. 2009. Ca2+ regulation of dynamin-independent endocytosis in cortical astrocytes. Journal of Neuroscience 29: 8063-8074.

Wang, Y., J. S. Qi, S. Kong, Y. Sun, J. Fan, M. Jiang, and G. Chen. 2009. BDNF-TrkB signaling pathway mediates the induction of epileptiform activity induced by a convulsant drug cyclothiazide. Neuropharmacology 57: 49-59.

Yuan, X., J. Yao, D. Norris, D. D. Tran, R. J. Bram, G. Chen, and B. Luscher. 2008. Calcium-modulating cyclophilin ligand regulates membrane trafficking of postsynaptic GABA(A) receptors. Mol. Cell Neurosci. 38(2): 277-289.

Deng, L., J. Yao, C. Fang, N. Dong, B. Luscher, and G. Chen. 2007. Sequential postsynaptic maturation governs the temporal order of GABAergic and glutamatergic synaptogenesis in rat embryonic cultures. Journal of Neuroscience 27(40): 10860-10869.