Research

Cognitive functions depend on the precise neural network formed by neurons in the brain. Neurons communicate through neurotransmission at the synapse, which comprises a presynaptic terminal that contains the active zone for neurotransmitter release, a postsynaptic apparatus that harbors a high density of receptors for relaying the signals to the target cell, and surrounding glial cells that modulate the efficacy of neurotransmission across the synapse. Synaptic dysfunction is associated with a number of neurodegenerative disorders, including Alzheimer’s disease and Parkinson disease. Therefore, the precise organization of synaptic proteins and the spatial and temporal coordination of synaptic signaling events are central research topics in neurobiology. We are interested to investigate
• the molecular basis of synapse development and plasticity in the central nervous system
• the pathophysiological mechanisms underlying neurodegeneration (e.g. Alzheimer’s disease)
• the biomarkers for the diagnosis and prognosis of Alzheimer’s disease and novel approaches for disease intervention
实验室链接：点击查看

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Positions available in Chen Lab at SIAT
The lab is interested in recruiting ambitious and highly motivated Postdoctoral Research Fellows, Graduate Students, and Research Assistants to study neural development, synaptic plasticity and neurodegeneration. Candidates should send their CV to yu.chen@siat.ac.cn.
招聘博士后&研究助理-陈宇课题组-中科院深圳先进院脑所： 点击查看招聘详情

Biography

Principal investigator at SIAT CAS since 2015
2010-2014, Research Assistant Professor, HKUST
2007-2010, Research Associate/Visiting Scholar, HKUST
2007, The Hong Kong University of Science and Technology, PhD
2002, Sun Yat-Sen University, BSc in Biochemistry

Selected publications

1. RanYi^#, ShuaiChen^#, Mingfeng Guan, Chunyan Liao, Yao Zhu, Jacque Pak Kan Ip, TaoYe^*, Yu Chen^*. (2024) A single-cell transcriptomic dataset of pluripotent stem cell-derived astrocytes via NFIB/SOX9 overexpression. Scientific Data 11:987.
2. Zhigang Zhang^#, Shuai Chen^#, Shirui Jun^#, Xirong Xu, Yuchuan Hong, Xifei Yang, Liangyu Zou, You-Qiang Song^*, Yu Chen^*, Jie Tu^*.MLKL-USP7-UBA52 signaling is indispensable for autophagy in brain through maintaining ubiquitin homeostasis. Autophagy DOI: 10.1080/15548627.2024.2395727
3. Hongjiao Wu, Yujie Yang, Wanying Yi, Yue Qiu, Shuangshuang Ma, Jinying Xu, Yingying Fan, Yuewen Chen, Yu Chen^*. (2024) Coronin 2B deficiency induces nucleolar stress and neuronal Apoptosis. Cell Death and Disease 15(6):457.
4. Mengqi Li^#, Mingfeng Guan^#, Jianbang Lin^#, Kaichuan Zhu^#, Jiayi Zhu, Ming Guo, Yinhu Li, Yefei Chen, Yijing Chen, Ying Zou, Daiqiang Wu, Junxin Xu, Wanying Yi, Yingying Fan, Shuangshuang Ma, Yuewen Chen, Jun Xu, Lixin Yang, Ji Dai, Tao Ye^*, Zhonghua Lu^*,Yu Chen^*. (2024) Early blood immune molecular alterations in cynomolgus monkeys with a PSEN1 mutation causing familial Alzheimer’s disease. Alzheimer’s & Dementia 2024;1-19. 
5. Yijing Chen^#, Yinhu Li^#, Yingying Fan, Shuai Chen, Li Chen, Yuewen Chen, Yu Chen^*. (2024) Gut microbiota-driven metabolic alterations reveal gut–brain communication in Alzheimer’s disease model mice. Gut Microbes16(1):2302310.
6. Huan Zhong^#, Xiaopu Zhou^#, Hyebin Uhm, Yuanbing Jiang, Han Cao, Yu Chen, Tiffany T.W. Mak, Ronnie Ming Nok Lo, Bonnie Wing Yan Wong, Elaine Yee Ling Cheng, Kin Y. Mok, Andrew Lung Tat Chan, Timothy C.Y. Kwok, Vincent C.T. Mok, Fanny C.F. Ip, John Hardy, Amy K.Y. Fu, Nancy Y. Ip^*. (2024) Using blood transcriptome analysis for Alzheimer’s disease diagnosis and patient stratification. Alzheimer’s&Dementia,https://doi.org/10.1002/alz.13691.
7. Jingyi Wang, Jianbang Lin, Yefei Chen, Jing Liu, Qiongping Zheng, Mao Deng, Ruiqi Wang, Yujing Zhang, Shijing Feng, Zhenyan Xu, Weiyi Ye, Yu Hu, Jiamei Duan, Yunping Lin, Ji Dai, Yu Chen, Yuantao Li, Tao Luo, Qian Chen^*, Zhonghua Lu^*.(2023) An ultra-compact promoter drives widespread neuronal expression in mouse and monkey brains. CELL REPORTS 42:113348.
8. Yue Chai^#, Sharon Shui Ying Lee^#, Amelle Shillington^*, Xiaoli Du, Catalina Ka Man Fok, Kam Chun Yeung, Gavin Ka Yu Siu, Shiyang Yuan, Zhongyu Zheng, Hayley Wing Sum Tsang, Shen Gu, Yu Chen,Tao Ye, Jacque Pak Kan Ip^*. (2023) Non-canonical C-terminal variant of MeCP2 R344W exhibits enhanced degradation rate. IBRO Neuroscience Reports 15: 218-224.
9. Yuzhen Ding, Qiangou Chen, Hui Shan, Jia Liu, Chunyu Lv, Yanhui Wang, Lin Yuan, Yu Chen, Ziyi Wang, Yuxin Yin, Kang Xiao^*, Jianchao Li^*, Wei Liu^*.(2023) SASH1: A novel Eph receptor partner and insights into SAM-SAM interactions. Journal of Molecular Biology 435(19):168243.
10. Xiaopu Zhou,Yu Chen, Fanny C. Ip, Yuanbing Jiang, Han Cao, Ge Lv, Huan Zhong, Jiahang Chen, Tao Ye, Yuewen Chen, Yulin Zhang, Shuangshuang Ma, Ronnie M. N. Lo, Estella P. S. Tong; Alzheimer’s Disease Neuroimaging Initiative; Vincent C T Mok, Timothy C Y Kwok, Qihao Guo, Kin Y Mok, Maryam Shoai, John Hardy, Lei Chen, Amy K Y Fu, Nancy Y Ip^*. (2023) Deep learning-based polygenic risk analysis for Alzheimer's disease prediction. Communications Medicine 3(1):49.
11. Yinhu Li^#, Yijing Chen^#, Yingying Fan, Yuewen Chen, Yu Chen^*. (2023) Dynamic network modeling of gut microbiota during Alzheimer’s disease progression in mice.Gut Microbes 15(1):2172672. 
12. Yuewen Chen^#, Zhenyan Xu^#, Jing Chen^#, Yue Qiu, Lin Yuan, Peng Liu, Jing Duan, Li Chen^*, Yu Chen^*.(2023) Coronin 2B regulates neuronal migration via Rac1-dependent multipolar–bipolar transition. Journal of Neuroscience 43 (2): 211-220.
13. Mingfeng Guan^#, Yue Chai^#, Ran Yi, Yuewen Chen, Jacque P.K. Ip, Tao Ye^*, Yu Chen^*. (2022) Generation of a homozygous ABCA7-knockout human iPSC line using the CRISPR/Cas9 system.Stem Cell Research 66:103000.
14. Yuanbing Jiang, Xiaopu Zhou, Hiu Yi Wong, Li Ouyang, Fanny C. F. Ip, Vicky M. N. Chau, Shun-Fat Lau, Wei Wu, Daniel Y. K. Wong, Heukjin Seo, Wing-Yu Fu, Nicole C. H. Lai, Yuewen Chen, Yu Chen, Estella P. S. Tong, Alzheimer’s Disease Neuroimaging Initiative, Vincent C. T. Mok, Timothy C. Y. Kwok, Kin Y. Mok, Maryam Shoai, Benoit Lehallier, Patricia Morán Losada, Eleanor O’Brien, Tenielle Porter, Simon M. Laws, John Hardy, Tony Wyss-Coray, Colin L. Masters, Amy K. Y. Fu^*, Nancy Y. Ip^*. (2022) An IL1RL1genetic variant lowers soluble ST2 levels and the risk effects of APOE-ε4 in female patients with Alzheimer’s disease. Nature Aging 2: 616–634.
15. Xueqi Qu, Li Lin, Wanying Yi, Changyu Sun, Yuewen Chen, Yu Chen^*. (2022) Early changes in transcriptomic profiles in synaptodendrosomes reveal aberrant synaptic functions in Alzheimer’s disease.International Journal of Molecular Sciences 23(16): 8888.
16. Han Cao, Xiaopu Zhou, Yu Chen, Fanny C F Ip, Yuewen Chen, Nicole C H Lai, Ronnie M N Lo, Estella P S Tong, Vincent C T Mok, Timothy C Y Kwok, Alzheimer’s Disease Neuroimaging Initiative; Amy K Y Fu, Nancy Y Ip^*. (2022) Association of SPI1haplotypes with altered SPI1 gene expression and Alzheimer's disease risk. Journal of Alzheimer’s Disease 86(4):1861-1873.
17. Kin Y Mok, East Asian Parkinson Disease Genomics Consortium. (2021) The east Asian Parkinson disease genomics consortium. The Lancet Neurology20(12):982.
18. David Goertsen^#, Nicholas C Flytzanis^#, Nick Goeden^#, Miguel R Chuapoco, Alexander Cummins, Yijing Chen, Yingying Fan, Qiangge Zhang, Jitendra Sharma, Yangyang Duan, Liping Wang, Guoping Feng, Yu Chen, Nancy Y Ip, James Pickel, Viviana Gradinaru^*. (2021) AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset. Nature Neuroscience25(1):106-115.
19. Lin Yuan, Wanying Yi, Changyu Sun, Shuangshuang Ma, Jiali Wang, Saijuan Liu, Yijing Chen, Yuewen Chen^*, Yu Chen^*. (2021) EphB2 activates CREB-dependent expression of Annexin A1 to regulate dendritic spine morphogenesis. Biochemical and Biophysical Research Communications584:107-115.
20. Chunyan Liao, Jinying Xu, Yu Chen^*, Nancy Y Ip^*. (2021) Retinal dysfunction in Alzheimer's disease and implications for biomarkers. Biomolecules11(8):1215.
21. Yijing Chen, Jinying Xu, Yu Chen^*. (2021) Regulation of neurotransmitters by the gut microbiota and effects on cognition in neurological disorders. Nutrients13(6):2099.
22. Yangyang Duan^#, Tao Ye^#, Zhe Qu, Yuewen Chen, Abigail Miranda, Xiaopu Zhou, Ka-Chun Lok, Yu Chen,Amy K Y Fu, Viviana Gradinaru, Nancy Y Ip^*. (2021) Brain-wide Cas9-mediated cleavage of a gene causing familial Alzheimer’s disease alleviates amyloid-related pathologies in mice. Nature Biomedical Engineering 6(2):168-180. 
23. Tao Ye, Yangyang Duan, Hayley W S Tsang, He Xu, Yuewen Chen, Han Cao, Yu Chen, Amy K Y Fu, Nancy Y Ip^*. (2021) Efficient manipulation of gene dosage in human iPSCs using CRISPR/Cas9 nickases. Communications Biology4(1):195.
24. Zhen Zhang^#, Liang Cui^#, Yanlu Huang, Yu Chen, Yuehua Li^*, Qihao Guo^*. (2021) Changes of regional neural activity homogeneity in preclinical Alzheimer's disease: compensation and dysfunction. Frontiers in Neuroscience15:646414.
25. Yuanbing Jiang, Xiaopu Zhou, Fanny C Ip, Philip Chan,Yu Chen, Nicole C H Lai, Kit Cheung, Ronnie M N Lo, Estella P S Tong, Bonnie W Y Wong, Andrew L T Chan, Vincent C T Mok, Timothy C Y Kwok, Kin Y Mok, John Hardy, Henrik Zetterberg, Amy K Y Fu, Nancy Y Ip^*. (2021) Large-scale plasma proteomic profiling identifies a high-performance biomarker panel for Alzheimer's disease screening and staging. Alzheimer’s＆Dementia 18(1):88-102.
26. Li Ouyang^#, Yu Chen^#, Ye Wang, Yuewen Chen, Amy K Y Fu, Wing-Yu Fu Nancy Y Ip^*. (2020) p39-associated Cdk5 activity regulates dendritic morphogenesis. Scientific Reports10(1):18746. 
27. Xiaopu Zhou, Yu Chen, Fanny C F Ip, Nicole C H Lai, Yolanda Y T Li, Yuanbing Jiang, Huan Zhong, Yuewen Chen, Yulin Zhang, Shuangshuang Ma, Ronnie M N Lo, Kit Cheung, Estella P S Tong, Ho Ko, Maryam Shoai, Kin Y Mok, John Hardy, Vincent C T Mok, Timothy C Y Kwok, Amy K Y Fu, Nancy Y Ip^*. (2020) Genetic and polygenic risk score analysis for Alzheimer's disease in the Chinese population. Alzheimer’s＆Dementia (Amsterdam Netherlands)12(1):e12074.
28. Yuewen Chen^#, Jinying Xu^#, Yulin Zhang, Shuangshuang Ma, Wanying Yi, Saijuan Liu, Xiaojun Yu, Jiali Wang, Yu Chen^*. (2020) Coronin 2B regulates dendrite outgrowth by modulating actin dynamics. FEBS Letters 594(18):2975-2987.
29. Yuewen Chen^#*, Jinying Xu^#, Xiaopu Zhou, Saijuan Liu, Yulin Zhang, Shuangshuang Ma, Amy K.Y. Fu, Nancy Y. Ip, Yu Chen^*. (2019) Changes of protein phosphorylation are associated with synaptic functions during the early stage of Alzheimer's disease. ACS Chemical Neuroscience 10(9):3986-3996. 
30. Xiaopu Zhou, Yu Chen, Kin Y. Mok, Timothy C. Y. Kwok, Vincent C. T. Mok, Qihao Guo, Fanny C. Ip, Yuewen Chen, Nandita Mullapudi, Alzheimer’s Disease Neuroimaging Initiative, Paola Giusti-Rodríguez, Patrick F. Sullivan, John Hardy, Amy K. Y. Fu, Yun Li, Nancy Y. Ip^*. (2019) Non-coding variability at the APOE locus contributes to the Alzheimer's risk. Nature Communications 10(1):3310.
31. Yu Chen^*, Amy K.Y. Fu, Nancy Y. Ip^*. (2018) Synaptic dysfunction in Alzheimer's disease: Mechanisms and therapeutic strategies. Pharmacology & Therapeutics 195:186-198.
32. Xiaopu Zhou^#, Yu Chen^#,Kin Y. Mok, Qianhua Zhao, Keliang Chen, Yuewen Chen, John Hardy, Yun Li, Amy K. Y. Fu, Qihao Guo^*, Nancy Y. Ip^*, for the Alzheimer’s Disease Neuroimaging Initiative. (2018) Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer’s disease pathogenesis. Proceedings of the National Academy of Sciences of the United States of America 115(8): 1697–1706.
33. Yu Chen^*, Zhuoyi Liang, Erkang Fei, Yuewen Chen, Xiaopu Zhou, Weiqun Fang, Wing-Yu Fu, Amy K.Y. Fu, Nancy Y. Ip^*. (2015) Axin regulates dendritic spine morphogenesis through Cdc42-dependent signaling.PLoS One 10(7): e0133115.
34. Yu Chen,Amy K.Y. Fu, Nancy Y. Ip^*. (2013) Axin: An emerging key scaffold at the synapse. IUBMB Life 65(8):685-91.
35. Yu Chen, Wing-Yu Fu, Jacque P.K. Ip^*, Tao Ye, Amy K.Y. Fu, Moses. V. Chao, Nancy Y. Ip. (2012) Ankyrin repeat-rich membrane spanning protein (Kidins220) is required for neurotrophin and ephrin receptor-dependent dendrite development.Journal of Neuroscience 32(24):8263-9.
36. Yu Chen, Amy K.Y. Fu, Nancy Y. Ip^*. (2012) Eph receptors at synapses: Implications in neurodegenerative diseases. Cellular Signalling24(3):606-11.
37. Jacque P. K. Ip, Lei Shi, Yu Chen, Yasuhiro Itoh, Wing-Yu Fu, Andrea Betz, Wing-Ho Yung, Yukiko Gotoh, Amy K.Y. Fu, Nancy Y. Ip^*. (2012) α2-chimaerin controls neuronal migration and functioning of the cerebral cortex through CRMP-2. Nature Neuroscience15(1):39-47.
38. Wei-Qun Fang, Jacque P.K. Ip, Rui Li, Yu-Pong Ng, Sheng-Cai Lin, Yu Chen, Amy K.Y. Fu^*, Nancy Y. Ip^*. (2011) Cdk5-mediated phosphorylation of Axin directs axon formation during cerebral cortex development. Journal of Neuroscience31(38):13613-24.
39. Hovik Farghaian, Yu Chen, Ada W.Y. Fu, Amy K.Y. Fu, Jacque P.K. Ip, Nancy Y. Ip, Ann M. Turnley, Adam R. Cole^*. (2011) Scapinin-induced inhibition of axon elongation is attenuated by phosphorylation and translocation to the cytoplasm. Journal of Biological Chemistry286(22):19724-34.
40. Amy K Fu, Kwok-Wang Hung, Wing-Yu Fu, Chong Shen, Yu Chen, Jun Xia, Kwok-On Lai, Nancy Y. Ip^*. (2011) APC^Cdh1mediates EphA4-dependent downregulation of AMPA receptors in homeostatic plasticity. Nature Neuroscience 14(2):181-9.
41. Peng Zhang, Pei-Chun Yu, Anthony H. K. Tsang, Yu Chen, Amy K. Y. Fu, Wing-Yu Fu, Kenny K. Chung^*, Nancy Y. Ip^*. (2010) S-Nitrosylation of cyclin-dependent kinase 5 (Cdk5) regulates its kinase activity and dendrite growth during neuronal development. Journal of Neuroscience30(43):14366-70.
42. Yu Chen^#*, Wing-Yu Fu^#*. (2009) EphB maintains dendritic spine morphology through focal adhesion kinase. Journal of Neuroscience29(42):13091-3.
43. Yu Chen, Amy K Y Fu, Nancy Y Ip^*. (2009) Bidirectional signaling of ErbB and Eph receptors at synapses. Neuron Glia Biology4(3):211-2.
44. Zelda H Cheung, Wing Hong Chin, Yu Chen, Yu Pong Ng, Nancy Y Ip^*. (2007) Cdk5 is involved in BDNF-stimulated dendritic growth in hippocampal neurons. PLoS Biology5(4): e63.
45. Wing-Yu Fu^#, Yu Chen^#, Mustafa Sahin, Xiao-Su Zhao, Lei Shi, Jay B Bikoff, Kwok-On Lai, Wing-Ho Yung, Amy K Y Fu, Michael E Greenberg, Nancy Y Ip^*. (2007) Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism.Nature Neuroscience 10(1):67-76.
46. Shuo Luo^#, Yu Chen^#, Kwok-On Lai, Juan Carlos Arévalo, Stanley C Froehner, Marvin E Adams, Moses V Chao, Nancy Y Ip^*. (2005) α-Syntrophin regulates ARMS localization at the neuromuscular junction and enhances EphA4 signaling in an ARMS-dependent manner. Journal of Cell Biology169(5):813-24.
47. Kwok-On Lai, Yu Chen, Hoi-Man Po, Ka-Chun Lok, Ke Gong, Nancy Y Ip^*. (2004) Identification of the Jak/Stat proteins as novel downstream targets of EphA4 signaling in muscle: implications in the regulation of acetylcholinesterase expression. Journal of Biological Chemistry279(14):13383-92.