- B.S., Fudan University
- Ph. D., Shanghai Institute of Physiology
- Stanford University
- Yale University
Honors and Awards:
- National Research Service Award from NIH at Stanford University
- Ohse Award at Yale University
In vivo reprogramming for brain repair
The major goal of our research is to develop innovative technologies for brain repair using our newly established in vivo cell conversion technology (Guo et al., Cell Stem Cell, 2014).
Reactive gliosis is a common pathological hallmark after brain injury or diseases. Currently there is no method available to reverse glial scars back to normal neural tissue. We have developed a novel technology to convert reactive glial cells, induced by brain injury or Alzheimer's disease, directly into functional neurons in mouse brain in vivo. This is achieved by expressing a single neural transcription factor NeuroD1 in glial cells. We further demonstrated that human astrocytes in culture can be directly converted into functional neurons, suggesting that our new technology may benefit millions of patients worldwide. Our in vivo cell conversion technology may have broad applications in neural repair after stroke, traumatic brain injury, spinal cord injury, Alzheimer's disease, Parkinson disease, Huntington disease, and glioma. We are currently developing gene therapy and small molecule therapy for human brain repair.
Autism and Schizophrenia
Many neurological disorders are caused by imbalance between excitation and inhibition. My lab investigates molecular mechanisms of neurodevelopmental disorders such as autism and schizophrenia, with a special focus on GABAergic synapses in the developing brain. GABA signaling emerges very early during embryonic brain development. GABA function changes from excitation in neonatal brain to inhibition in adult brain. We have generated a transgenic mouse model with GABAergic deficits to study the functional role of GABA in schizophrenia and related neuropsychiatric disorders. We also employ induced pluripotent stem cells (iPSCs) from autism patients to study GABA function in autism.
Neurodegenerative disorders afflict millions of people worldwide and have become an enormous socioeconomic burden for society. We are investigating molecular mechanisms underlying memory loss using a variety of transgenic mouse models for Alzheimer's disease. Our recent studies discovered a high GABA content in reactive astrocytes and an abnormal GABA inhibition in the Alzheimer's brain. We also identified a novel drug target for the treatment of Alzheimer's disease (Wu et al., Nature Communications, 2014). Our novel findings may explain why previous clinical trials focusing on reducing amyloid plaques have failed, and suggest that a cocktail approach that will correct multiple dysfunctions in the Alzheimer's brain may be an ultimate solution for this complex neurodegenerative disorder.
Zhexing Wen*, Ha Nam Nguyen*, Ziyuan Guo*, Matthew Lalli, Xinyuan Wang, Yijing Su, Nam-Shik Kim, Ki-Jun Yoon, Jaehoon Shin, Ce Zhang, Georgia Makri, David Nauen, Humei Yu, Cheng-Hsuan Chiang, Nadine Yoritomo, Kozo Kaibuchi, Christopher Ross, Jizhong Zou, Kimberly Christian, Linzhao Cheng, Russell Magolis, Gong Chen, Kenneth Kosik, Elmer Guzman, Hongjun Song, and Guo-li Ming. Synaptic dysregulation in a human iPS cell model of mental disorders. Nature, E-pub Aug. 17, 2014.
Zheng Wu, Ziyuan Guo, Marla Gearing, Gong Chen. (2014) Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an Alzheimer's disease model. Nature Communications, June 13, 2014. (http://www.nature.com/ncomms/2014/140613/ncomms5159/full/ncomms5159.html)
Ziyuan Guo, Lei Zhang, Zheng Wu, Yuchen Chen, Fan Wang, and Gong Chen. (2014) In Vivo Direct Reprogramming of Reactive Glial Cells into Functional Neurons after Brain Injury and in an Alzheimer’s Disease Model. Cell Stem Cell, 14: 188-202. E-pub on Dec. 19, 2013.
Nature Research highlight: http://www.nature.com/nature/journal/v505/n7482/full/505134b.html
Science China (Chinese 中文）： http://www.sciencemagchina.cn/highlights131220.aspx
Xin Tang, Li Zhou, Alecia M. Wagner, Maria C.N. Marchetto, Alysson R. Muotri, Fred H. Gage, and Gong Chen. (2013) Astroglial cells regulate the developmental timeline of human neurons differentiated from induced pluripotent stem cells. Stem Cell Research, E-pub May 16. (http://www.sciencedirect.com/science/article/pii/S1873506113000512)
Chicheng Sun, Lei Zhang, and Gong Chen. (2013) An unexpected role of neuroligin-2 in regulating KCC2 and GABA functional switch. Mol Brain, 6:23. (http://www.molecularbrain.com/content/6/1/23)
,,,,,,, and Homeostatic competition between phasic and tonic inhibition. J. Biol. Chem. First Published on July 9, 2013, doi:10.1074/jbc.M113.491464. (http://www.jbc.org/content/early/2013/07/09/jbc.M113.491464.full.pdf/)
Yajie Sun, Zheng Wu, Shuzhen Kong, Dongyun Jiang, Anar Pitre, Yun Wang, and Gong Chen. (2013) Regulation of epileptiform activity by two distinct subtypes of extrasynaptic GABAA receptors. Mol Brain, 6:21. (http://www.molecularbrain.com/content/6/1/21)
Wang R, McGrath BC, Kopp RF, Roe MW, Tang X, Chen G, Cavener DR. (2013) Insulin secretion and Ca2+ dynamics in β-cells are regulated by PERK eIF2α kinase in concert with calcineurin. J Biol Chem, 2013 Nov 22; 288(47):33824-36. doi: 10.1074/jbc.M113.503664. Epub 2013 Oct 10. (http://www.jbc.org/content/288/47/33824.full.pdf+html)
A. Alachkar, D. Jiang, M. Harrison, Y. Zhou, G. Chen, and Y. Mao. (2013) An EJC Factor RBM8a Regulates Anxiety Behaviors. Current Molecular Medicine 2013, 13, 1-13. (http://www.ncbi.nlm.nih.gov/pubmed/23638902)
Wu X, Wu Z, Ning G, Guo Y, Ali R, Macdonald RL, De Blas AL, Luscher B, Chen G. (2012) gamma-Aminobutyric Acid Type A (GABAA) Receptor Alpha Subunits Play a Direct Role in Synaptic versus Extrasynaptic Targeting. J Biol Chem. 287(33): p. 27417-27430. (Paper of the Week) (http://www.jbc.org/content/287/33/27417.long)
Joseph Cichon, Chi-Cheng Sun, Ben Chen, Min Jiang, Xiangyun Amy Chen, Yajie Sun, Yun Wang*, and Gong Chen*. (2012) Cofilin Aggregation Blocks Intracellular Trafficking and Induces Synaptic Loss.
J Biol Chem. 287(6): 3919–3929. (http://www.jbc.org/content/287/6/3919.long)
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. (http://www.nature.com/nature/journal/v473/n7346/full/nature09915.html)
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, 20(15): 3042–3051.
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.
Yazhou Sun, Yaqiong Wang, Yi Hu, Gong Chen, Hong Ma. (2011). Comparative analysis of neural transcriptomes and functional implication of unannotated intronic expression. BMC Genomics, 2011 Oct 10;12:494.
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. (http://www.sciencedirect.com/science/article/pii/S0092867410011864)
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. (http://www.nature.com/neuro/journal/v13/n10/full/nn.2634.html)
Kong S, Qian B, Liu J, Fan M, Chen G, Wang Y. (2010). Cyclothiazide induces seizure behavior in freely moving rats. Brain Res. 1355:207-213.
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. (http://www.pnas.org/content/106/31/12741.long)
Jiang, M. and G. Chen. (2009) Ca2+ regulation of dynamin-independent endocytosis in cortical astrocytes. Journal of Neuroscience 29: 8063-8074. (http://www.jneurosci.org/content/29/25/8063.full.pdf)
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. (http://www.jneurosci.org/content/27/40/10860.long)
Dong, N., Qi, J., Chen, G. (2007). Molecular reconstitution of functional GABAergic synapses with expression of neuroligin-2 and GABAA receptors. Mol. Cell. Neurosci. 35: 14 - 23.
Wendou Yu, Min Jiang, Celia P. Miralles, Gong Chen and Angel L. de Blas. (2007). Gephyrin clustering is required for the stability of GABAergic synapses. Mol. Cell. Neurosci. 36(4):484-500.
Fang, C., Deng, L., Keller, C., Fukata, M., Fukata, Y., Chen, G., and Lüscher, B. (2006). GODZ-mediated palmitoylation of GABAA receptors is required for normal assembly and function of GABAergic inhibitory synapses. Journal of Neuroscience 26(49): 12758-12768 .
Qi, J. S., Yao, J., Fang, C., Lüscher, B., and Chen, G. (2006). Downregulation of tonic GABA currents following epileptogenic stimulation of rat hippocampal cultures. Journal of Physiology 577(2): 579-590.
Yao, J., Qi, J. S., and Chen, G. (2006). Actin-dependent activation of presynaptic silent synapses contributes to long-term synaptic plasticity in developing hippocampal neurons. Journal of Neuroscience, 26 (31): 8137 – 8147. (http://www.jneurosci.org/content/26/31/8137.full.pdf)
Jiang, M. and Chen, G. (2006). High Ca2+-phosphate transfection efficiency in low-density neuronal cultures. Nature Protocols. Vol. 1. (No. 2) 695 – 700. (Invited article)
Qi, J.S., Wang, Y., Jiang M., Warren, W., and Chen, G. (2006). Cyclothiazide induces robust epileptiform activity in rat hippocampal neurons both in vitro and in vivo. Journal of Physiology 571(3): 605-618.
Zhou, J., Pfaff, D. W., and Chen, G. (2005). Sex differences in estrogenic regulation of neuronal activity in neonatal cultures of ventromedial nucleus of the hypothalamus. PNAS 102: 14907-14912.
Alldred, M.J., Mulder-Rosi, J., Lingenfelter, S. E., Chen, G., and Lüscher, B. (2005) Distinct g2 Subunit Domains Mediate Clustering and Synaptic Function of Postsynaptic GABAA Receptors and Gephyrin. Journal of Neuroscience 25(3): 594-603.
Jiang, M., Deng, L.B., and Chen, G. (2004). High Ca2+-phosphate transfection efficiency enables single neuron gene analysis. Gene Therapy 11:1303-1311.
Cao, Y-Q., Piedras-Renteria, E., Smith, G. B., Chen, G., Harata, N. C., Tsien, R. W. (2004). Presynaptic Ca2+ channels compete for channel type-preferring slots in altered neurotransmission arising from Ca2+ channelopathy. Neuron 43: 387-400. (http://www.sciencedirect.com/science/article/pii/S0896627304004362)
Chen, G., Harata, N. and Tsien, R. W. (2004). Paired-pulse depression of unitary quantal amplitude at single hippocampal synapses. PNAS 101: 1063-1068. (http://www.pnas.org/content/101/4/1063.full.pdf)
Deng, L. B., and Chen, G. (2003). Cyclothiazide potently inhibits g-aminobutyric acid type A receptors in addition to enhancing glutamate responses. PNAS 100 (22): 13025-13029.
Chen, Y., Deng, L. B., Maeno-Hikichi, Y., Lai, M. Z., Chang, S. H., Chen, G., and Zhang, J. F. (2003). Formation of an endophilin-Ca2+ channel complex is critical for clathrin-mediated synaptic vesicle endocytosis. Cell 115: 37-48. (http://www.sciencedirect.com/science/article/pii/S0092867403007268)