个人简介

陈功( Gong Chen )博士于1987 年毕业于上海复旦大学，随后师从中国科学院上海生理研究所冯德培院士攻读博士学位。先后在耶鲁大学和斯坦福大学进行博士后研究。2002年加入宾夕法尼亚州立大学( Pennsylvania State University )做教授，2013年升任维恩·魏勒曼冠名主任教授（讲席教授）。2019年辞去宾夕法尼亚州立大学的终身教授席位，全职加入暨南大学粤港澳中枢神经再生研究院，建立大脑修复中心，为解决重大脑疾病探索原位神经再生的新途径。

主要成就

陈功教授是国际上最早在成年哺乳类动物上利用大脑内源性可分裂的星形胶质细胞（astrocyte）原位直接转分化为功能性神经元的开创者之一。 2013年底在线发表了国际上首篇运用神经转录因子NeuroD1在老年痴呆症模型小鼠上原位再生神经元的工作，被Cell Stem Cell评为2014年度最佳论文，是目前该领域最具影响力的论文之一。随后，在小鼠和大鼠疾病模型上发表了一系列有关大脑、脊髓、和视网膜中的原位神经再生工作。2020年，又首次在国际上报道了在非人灵长类猕猴大脑里实现星形胶质细胞向神经元的原位直接转分化的工作。陈功教授团队还创造性地发明了一种小分子组合物，可将体外培养的人脑来源的星形胶质细胞直接转化为功能性神经元。2014 年，陈功教授在华盛顿神经科学大会上主持了世界上首次“在体细胞转化” 的专题报告会，标志着再生医学领域的一个新的里程碑。2016年受邀 Neuron 杂志发表了关于大脑原位神经再生技术的前瞻性综述，为这一新领域的发展指明了方向。陈功教授创办的NeuExcell神曦生物公司获得2023年度全国创新创业大赛总决赛一等奖，2024年实现全球首例患者接受NeuroD1基因治疗的里程碑。目前，陈功教授领导的大脑修复中心主要研究原位神经再生技术在治疗脑中风，老年痴呆症，脑胶质瘤，帕金森综合症，亨廷顿舞蹈症，脑损伤，渐冻症（ALS），脊髓损伤，以及眼科疾病等重大中枢神经疾病中的应用及临床转化。

代表性论文

1.       Chen G.   In vivo neuroregenerative gene therapy to treat neurodegenerative disorders. Mol Ther. 2024, accepted for publication.

2.       Xiang Zongqin, He Shu, Chen Rongjie, Liu Shanggong, Liu Minhui, Xu Liang, Zheng Jiajun, Jiang Zhouquan, Ma Long, Sun Ying, Qin Yongpeng, Chen Yi, Li Wen, Wang Xiangyu, Chen Gong, Lei Wenliang. Two-photon live imaging of direct glia-to-neuron conversion in the mouse cortex. Neural Regen Res. 2024 Aug 1;19(8):1781-1788.   doi: 10.4103/1673-5374.386401. Epub 2023 Oct 2.

3.       Zhouquan Jiang, Jing Wang, Yongpeng Qin, et al., Gong Chen and Wenliang Lei.   A nonhuman primate model with Alzheimer’s disease‑like pathology induced by hippocampal overexpression of human tau.   Alzheimer’s Research & Therapy (2024) 16:22.   https://doi.org/10.1186/s13195-024-01392-0  

4.       Liu M, Xu Y, Bai X, et al., Gong Chen.  Efficient Dlx2-mediated astrocyte-to-neuron conversion and inhibition of neuroinflammation by NeuroD1. Develop Biol, 2024: 1-17.   DOI: 10.1002/dneu.22951

5.       Qing He, Zhen Wang, et al., Gong Chen.   Characteristic changes in astrocyte properties during astrocyte-to-neuron conversion induced by NeuroD1/Ascl1/Dlx2. Neural Regen Res, May 13, 2024.  https://doi.org/10.4103/NRR.NRR-D-23-01897

6.       Xiaosong He, Xin Wang, Hui Wang, et al., Wen Li, Zheng Wu, Gong Chen. NeuroD1 regulated endothelial gene expression to modulate transduction of AAV-PHP.eB and recovery progress after ischemic stroke. Aging Disease, 2023, 14:6.

7.       Yaowei Guo, Junliang Chen, Wenyu Ji, et al., Gong Chen and Zheng Wu. High-titer AAV disrupts cerebrovascular integrity and induces lymphocyte infiltration in adult mouse brain. Molecular Therapy-Meth Clin Develop, 2023, 31: 1011102.

8.       Di Xu, Li-Ting Zhong, Hai-Yang Cheng, et al., Gong Chen, Ying Xu. Overexpressing NeuroD1 reprograms Müller cells intovarious types of retinal neurons.   Neural Regen Res, October 2022.     https://doi.org/10.4103/1673-5374.355818

9.       Transcriptomic analyses of NeuroD1-mediated astrocyte-to-neuron conversion. Ma NX, Puls B, Chen G. Dev Neurobiol. 2022 Jul;82(5):375-391.

10.    Zheng JJ, Li T, Qi S, Qin B, Yu J, Chen G. Neuroregenerative gene therapy to treat temporal lobe epilepsy in a rat model. Prog Neurobiol. 2021 Nov 28;208:102198.    doi: 10.1016/j.pneurobio.2021.102198.

11.    Wang T, Liao JC, Wang X, Wang QS, Wan KY, Yang YY, He Q, Zhang JX, Chen G, Li W. Unexpected BrdU inhibition on astrocyte-to-neuron conversion. Neural Regen Res. 2021 December, ePub. doi: 10.4103/1673-5374.325747. PMID: 34916438.

12.    Chen G. In vivo confusion over in vivo conversion. Mol Ther. 2021 Nov 3;29(11):3097-3098. doi: 10.1016/j.ymthe. 2021.10.017. Epub 2021 Oct 25.

13.    Wang X, Pei Z, Hossain A, Bai Y, Chen G. Transcription factor-based gene therapy to treat glioblastoma through direct neuronal conversion. Cancer Biol Med. 2021 Mar 23;18(3):860-74.    doi: 10.20892/j.issn.2095-3941.2020.0499.

14.    Xiang Z, Xu L, Liu M, Wang Q, Li W, Lei W, Chen G. Lineage tracing of direct astrocyte-to-neuron conversion in the mouse cortex. Neural Regen Res. 2021 Apr;16(4):750-756.    doi: 10.4103/1673-5374.295925.

15.    Wang H, Xu L, Lai C, Hou K, Chen J, Guo Y, Sambangi A, Swaminathan S, Xie C, Wu Z, Chen G. Region-specific distribution of Olig2-expressing astrocytes in adult mouse brain and spinal cord.  Mol Brain.  2021 Feb 17;14(1):36.      doi: 10.1186/s13041-021-00747-0.

16.    Zheng Wu, Matthew Parry, Xiao-Yi Hou, Min-Hui Liu, Hui Wang, Rachel Cain, Zi-Fei Pei, Yu-Chen Chen, Zi-Yuan Guo, Sambangi Abhijeet, Gong Chen. Gene therapy conversion of striatal astrocytesinto GABAergic neurons in mouse models of Huntington’s disease. Nature Communications, 2020, 11(1105):1-18.

17.    Yu Tang, Qiuyu Wu, Mang Gao, Esther Ryu, Zifei Pei, Samuel T Kissinger, Yuchen Chen, Abhinav K Rao, Zongqin Xiang, Tao Wang, Wen Li, Gong Chen, Alexander A Chubykin. Restoration of visual function and cortical connectivity after ischemic injury through NeuroD1-mediated gene therapy. Frontiers in Cell and Developmental Biology, 9:1-17.   18 Aug 2021.    DOI: 10.3389/fcell.2021.720078

18.    Lei Zhang, Zhuofan Lei, Ziyuan Guo, Zifei Pei, Yuchen Chen, Fengyu Zhang, Alice Cai, Gabriel Mok, Grace Lee, Vishal Swaminathan, Fan Wang, Yuting Bai, and Gong Chen.  Development of Neuroregenerative Gene Therapy to Reverse Glial Scar Tissue Back To Neuron-Enriched Tissue.  Frontiers Cell Neurosci., 14:1-19.   Published:  05 Nov 2020. (doi: 10.3389/fncel.2020.594170).

19.    Long-Jiao Ge, Fu-Han Yang, Wen Li, Tao Wang, Yu Lin, Jie Feng, Nan-Hui Chen, Min Jiang, Jian-Hong Wang, Xin-Tian Hu, Gong Chen. In Vivo Neuroregeneration to Treat Ischemic Stroke Through NeuroD1 AAV-Based Gene Therapy in Adult Non-Human Primates.   Frontiers Cell Develop Biol, 8:1-21, 05 Nov 2020.  DOI: 10.3389/fcell.2020.590008

20.    Yu-Chen Chen, Ning-Xin Ma, Zi-Fei Pei, Zheng Wu, Fabricio H. Do-Monte, Susan Keefe, Emma Yellin, Miranda S. Chen, Jiu-Chao Yin, Grace Lee, Angélica Minier- Toribio, Yi Hu, Yu-Ting Bai, Kathryn Lee, Gregory J. Quirk, Gong Chen.    A NeuroD1 AAV-Based Gene Therapy For Functional Brain Repair After Ischemic Injury Through In Vivo Astrocyte-To-Neuron Conversion.   Molecular Therapy, 2020,  28:1-18.       (Sept. 6, 2019 online published)

News Press:   https://scienmag.com/gene-therapy-helps-functional-recovery-after-stroke/

Highlighted by NIH Director’s Blog:

https://directorsblog.nih.gov/2019/09/24/gene-therapy-shows-promise-repairing-brain-tissue-damaged-by-stroke/

21.    Brendan Puls, Yan Ding, Fengyu Zhang, Mengjie Pan, Zhuofan Lei, Zifei Pei, Mei Jiang, Yuting Bai, Cody Forsyth, Morgan Metzger, Tanvi Rana, Lei Zhang, Xiaoyun Ding, Matthew Keefe, Alice Cai, Austin Redilla, Michael Lai, Kevin He, Hedong Li, and Gong Chen.  Regeneration of functional neurons after spinal cord injury via in situ NeuroD1-mediated astrocyte-to-neuron conversion.    Frontiers Cell Develop Biol, 8:1-18.   Dec. 16, 2020.   doi: 10.3389/fcell.2020.591883

22.    Liu MH,Li W, Zheng JJ, Xu YG, He Q, Chen G. Differential neuronal reprogramming of astrocytes in the grey matter and white matter. Neural Regen Res. 2020 Feb;15(2):342-351.

23.    Muhua Lai, Mengjie Pan, Longjiao Ge, Jingmin Liu, Junyao Deng, Xianghai Wang, Lixia Lia, Jinkun Wen, Dandan Tan, Haowen Zhang, Xiaofang Hua, Lanya Fu,Yizhou Xu, Zhenlin Li, Xiaozhong Qiu, Gong Chen, Jiasong Guo.   NeuroD1 overexpression in spinal neurons accelerates axonal regeneration after sciatic nerve injury. Experimental Neurology. May 2020．DOI: 10.1016/j.expneurol.2020.113215

24.    Jian Chen, Binbin Dong, Xiaoyi Feng, Dongyun Jiang, Gong Chen, Cheng Long,  Li Yang.   Aberrant mPFC GABAergic synaptic transmission and fear behavior in neuroligin-2 R215H knock-in mice. Brain Research. 2020-03. DOI: 10.1016/j.brainres.2020.146671

25.    Lei W, Li W, Ge L, Chen G. Non-engineered and Engineered Adult Neurogenesis in Mammalian Brains. Front Neurosci. 2019 Feb 21;13:131.

26.    Yin, J.C., Zhang, L., Ma, N.X., Wang, Y., Lee, G., Hou, X.Y., Lei, Z.F., Zhang, F.Y., Dong, F.P., Wu, G.Y., and Chen, G.  (2019)  Chemical Conversion of Human Fetal Astrocytes into Neurons through Modulation of Multiple Signaling Pathways.   Stem Cell Reports, Feb. 7, 2019, onlinepublication.

DOI:https://doi.org/10.1016/j.stemcr.2019.01.003

News press:   https://science.psu.edu/news-and-events/2019-news/Chen2-2019

27.    Zheng Wu, Qingwei Huo, Liang Ren, Fengping Dong, Mengyang Feng, Yue Wang, Yuting Bai, Bernhard Lüscher, Sheng-Tian Li, Guan-Lei Wang, Cheng Long, Yun Wang, Gangyi Wu & Gong Chen. (2019).Gluconate suppresses seizure activity in developing brains by inhibiting CLC-3 chloride channels. Molecular Brain,  Volume 12, Article #: 50 (2019).

News press:   https://www.eurekalert.org/pub_releases/2019-05/ps-ndc051519.php

28.  Hedong Li and Gong Chen. (2016)  In vivo reprogramming for CNS repair: Regenerating neurons from endogenous glial cells.   Neuron, 91:728-738. (Invited review)

29.  Xin Tang, Julie Kim, Li Zhou, Eric Wengert, Lei Zhang, Zheng Wu, Cassiano Carromeu, Alysson R. Muotri, Maria C. N. Marchetto, Fred H. Gage, and Gong Chen.  (2016)   KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome.          Proc Natl Acad Sci U S A. Epub: 2016 Jan 5.

News press:  http://news.psu.edu/story/386151/2016/01/04/research/discovery-new-drug-target-could-lead-novel-treatment-severe-autism

30.  Lei Zhang, Jiu-Chao Yin, Hana Yeh, Ning-Xin Ma, Grace Lee, Xiangyun Amy Chen, Yanming Wang, Li Lin, Li Chen, Peng Jin, Gang-Yi Wu* and Gong Chen*.  (2015)  Small Molecules Efficiently Reprogram Human Astroglial Cells into Functional Neurons.   Cell Stem Cell, 17:1-13, E-Pub on Oct. 15, 2015.

The article:  http://www.cell.com/cell-stem-cell/pdf/S1934-5909(15)00419-1.pdf

News press:  http://science.psu.edu/news-and-events/2015-news/Chen10-2015

31.    Ziyuan Guo, Lei Zhang, Zheng Wu, Yuchen Chen, Fan Wang, and Gong Chen. (2014) In vivo direct reprogramming reactive glial cells into functional neurons after brain injury and in an Alzheimer’s disease model.   Cell Stem Cell, 14: 188-202. E-pub Dec. 19, 2013.  Selected as BEST of 2014 article by Cell Stem Cell in 2015.

Nature Highlight:  http://www.nature.com/nature/journal/v505/n7482/full/505134b.html

Cell Stem Cell preview: http://www.cell.com/cell-stem-cell/abstract/S1934-5909(14)00011-3

News press:  http://medicalxpress.com/news/2013-12-brain-injury-alzheimer-disease.html

32.    Zheng Wu, Ziyuan Guo, Marla Gearing, and 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.

News press:   http://medicalxpress.com/news/2014-06-alzheimer-memory-deficit-excessive-inhibition.html

33.    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, 515(7527):414-8. doi: 10.1038/nature13716. Epub 2014 Aug 17.

News press:   http://neurosciencenews.com/synaptic-growth-disc1-neurodevelopment-1224/

34.  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, 11(2):743-757. Cover article.  Ranked as the most downloaded article in the journal website immediately after publication.

News press: http://www.sciencedaily.com/releases/2013/06/130606141130.htm

35.  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.     [Selected as “Paper of the week” by Editors].        

Press release: http://www.sciencedaily.com/releases/2012/08/120808093854.htm

36.    Kristen Brennand, Anthony Simone, Jessica Jou, Chelsea Gelboin-Burkhart, Ngoc Tran, Sarah Sangar, Yan Li, Yangling Mu, Gong Chen, Diana Yu, Shane McCarthy, Jonathan Sebat, Fred H. Gage. (2011). Modeling schizophrenia using human induced pluripotent stem cells.  Nature, 473(7346): 221-225.   Press release and news coverage:

http://science.psu.edu/news-and-events/2011-news/Chen4-2011

http://www.nature.com/news/2011/110413/full/news.2011.232.html

37.    Maria C. N. Marchetto, Cassiano Carromeu, Allan Acab, Diana Yu, Gene Yeo, Yangling Mu, Gong Chen, Fred H. Gage & Alysson R. Muotri.  (2010).  A model for neural development and treatment of Rett Syndrome using human induced pluripotent stem cells. Cell, 143:527-539.   Press release and news coverage:

http://science.psu.edu/news-and-events/2010-news/Chen11-2010 

http://www.msnbc.msn.com/id/40134442#.ULD71-S5NpU

38.    Jiaping Gu, Chi Wai Lee, Yanjie Fan, Daniel Komlos, Xin Tang, Chicheng Sun, Kuai Yu, H. Criss Hartzell, Gong Chen,   James R. Bamburg, and James Q. Zheng.   (2010).  ADF/Cofilin-Mediated Actin Dynamics Regulate AMPA Receptor Trafficking during Synaptic Plasticity.   Nature Neuroscience, 13: 1208–1215. 

39.    Han, X.W., Wu, X., Chung, W.Y., Li, T., Nekrutenko, A., Altman, N.S., Chen^*, G., and Ma^*, H.  (2009).  Transcriptome of embryonic and neonatal mouse cortex by high-throughput RNA sequencing. PNAS 106:12741-12746.  (Corresponding author)

Press release:  http://science.psu.edu/news-and-events/2009-news/active-genes-discovered-in-the-developing-mammal-brain

http://www.nsf.gov/news/news_summ.jsp?cntn_id=115315

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

41.    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.

42.    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)

43.    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.  

44.    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.  

45.    Chen, G., Harata, N. and Tsien, R. W.  (2004). Paired-pulse depression of unitary quantal amplitude at single hippocampal synapses. PNAS 101: 1063-1068.  

46.    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.  

47.    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.