• 陈永昌（Yongchang Chen)

    教授，博士生导师，国家杰出青年科学基金获得者

    昆明理工大学生命科学与技术学院院长

    灵长类转化医学研究院神经发育与疾病课题组PI

    Ph.D., Professor, Doctoral Advisor

    Principal Investigator in Non-human Primate Models of CNS disease

    Dean & Professor of Faculty of Life Science and Technology, KUST

    一、学习及工作经历 Education/Professional Experience

    1996-2003年，甘肃农业大学，动物科学/动物遗传育种与繁殖，本科/硕士

    2006-2010年，中国科学院昆明动物研究所，动物学，博士

    2003-2014年，中国科学院昆明动物研究所，助研、副研究员

    2014年-，昆明理工大学灵长类转化医学研究院，教授

    2023年-，昆明理工大学生命科学与技术学院，教授，院长

     

    1996-2003 Gansu Agricultural University, Bachelor's Degree/Master's Degree

    2006-2010 Kunming Institute of Zoology, Chinese Academy of Sciences, Doctor’s Degree

    2003-2014 Kunming Institute of Zoology, Chinese Academy of Sciences, Assistant and associate professor

    2014-present Institute of Primate Translational Medicine, Kunming University of Science and Technology, Professor

    2023-present, Dean and Professor, Faculty of Life Science and Technology, Kunming University of Science and Technology.

    二、科研领域描述 Description of Research Field

    脑科学研究是生命及健康科学研究中最复杂、最重要、也是最具有吸引力的研究领域。因与人类在基因组相似度、脑结构及脑功能、生殖生理等方面具有高度的相似性，灵长类动物被认为是研究人类健康最理想的实验动物，也已被越来越多的研究结果所证实。利用灵长类动物模型开展脑发育及神经系统疾病的发病机理研究、探索有效的预防及治疗办法，是实现从基础研究到临床前研究，进而实现临床转化的重要桥梁。本研究团队多年来一直致力于神经系统疾病的灵长类动物模型构建、遗传学及行为学表型鉴定、发病机理及治疗策略的探索等方面的研究。现已构建了高效稳定的基因修饰灵长类动物模型研究平台、在世界上首次实现了对灵长类动物进行靶向基因修饰。目前已建立了多种神经系统疾病的灵长类动物模型，包括杜氏肌营养不良症（Duchenne Muscular Dystrophy，DMD）及瑞特综合征（Rett Syndrome，RTT）的基因编辑猴模型。相关研究结果发表在包括Cell、Cell Stem Cell、Cell Research、Human Molecular Genetics等杂志上。

     

    Brain science is one of the most complex, important and attractive field in life and health science research. Primates are considered as the optimal experimental animals to study human health for its high similarity with human in genome, brain structure and function, and reproductive physiology. The use of NHP animal model to study brain development and neurological disease pathogenesis research, and to explore effective prevention and treatment methods, is the important bridge to deepen the brain science research from basic research to preclinical research, thus achieving clinical translation. Our research team has been working on the construction of primate models of neurological diseases, genetics and behavioral phenotypic identification, pathogenesis and therapeutic strategies for many years. A highly efficient and stable research platform of gene modified primate animal models has been established and the first targeted gene modification of primates in the world was achieved. The primate models of different neurological diseases were generated, including Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD) and Rett syndrome (RTT). The results of these studies were published in Cell (2014, 2017), Cell Stem Cell (2014, 2015), Cell Research (2015, 2017), Human Molecular Genetics (3 papers in 2015) and other magazines.

    Our research interests include establishment of gene targeted monkey models of the nervous system disease, molecular mechanism of early developmental abnormalities and neurological diseases, genetic modification and cell therapy using genetically modified primate models, and primate reproductive biology.

    三、主要兴趣及研究方向

    1、基因修饰技术构建人类神经系统疾病的灵长类动物模型

    以神经系统为主要着眼点，针对与遗传相关的神经发育性疾病以及神经退行性疾病，选择关键基因及在临床上高发的亚型，优化靶向基因修饰，获得与人类患者更为接近的猴模型。通过分子水平的检测对模型进行鉴定，并针对不同模型特点持续监测相关行为学、影像学、生理生化指标等变化情况，并与正常对照进行对比，分析疾病发生发展的特点。

     

    2、早期发育异常及神经系统疾病发病的分子机理研究

    根据灵长类胚胎早期发育特点，利用基因靶向修饰（敲入、敲除、抑制、过表达等）对神经管发育发挥重要调控作用的关键基因开展功能学研究，从体外（胚胎干细胞或诱导性多能干细胞）和体内（早期植入后胚胎）两条途径探讨神经管极性形成过程中相关信号通路及营养代谢通路对神经管闭合的影响作用。此外，对于已经建立的神经系统疾病猴模型，通过分析目的基因及蛋白在修饰后的表达变化，以及相应的转录组动态变化情况，深入研究遗传性神经系统疾病的致病机理。

     

    3、利用基因修饰灵长类动物模型探索基因修复及细胞治疗

    利用小鼠模型开展的药物试验，最终成功应用于临床的比例不足5%。其原因是除了人与鼠在遗传、代谢及神经系统的巨大差异外，基因表达调控模式也存在巨大差异。利用良好的灵长类动物模型对目前难以治愈的复杂疾病开展新的治疗研究具有显著优势。将患病细胞靶基因进行修正、结合诱导性多能干细胞及其分化潜能是探索细胞替代治疗的新思路。通过转录组分析发现的可能靶标，以及其他研究中发现的小分子等也都为新疗法的建立提供了方向。

     

    4、灵长类动物生殖生物学

    灵长类动物与人类在神经系统及生殖生理上均高度相似，利用灵长类动物开展生殖机理研究、建立生殖调控新技术体系等方面具有重要意义。灵长类动物生殖生理操控是开展配子操作相关研究的基础，本团队多年来致力于建立高效、稳定的配子操作体系，先后建立了猕猴及食蟹猴的超排及胚胎移植、婴幼猴辅助哺育及护理、小猴训练、多胎减胎、利用母猴外周血中游离DNA监测胎猴性别及基因修饰阳性率等标准化流程。在此基础上，还将进一步探索灵长类动物生殖内分泌、性腺发育及配子发生等基础科学问题。

    四、主持并正在执行的科研项目

    1.云南省人社厅，云南省万人计划“云岭学者”，2020-2024，200万，主持

    2.国家自然科学基金重点项目，81930121，基于猴模型的杜氏肌营养不良症（DMD）基因治疗临床前研究，2020-2024，297万，主持

    3.云南省科技厅创新团队，202005AE160019，云南中科灵长类生物医学重点实验室神经疾病非人灵长类模型临床前研究省创新团队，100万，主持

    4.科技创新2030-“脑科学与类脑研究”重大项目，2021ZD0200903，脑疾病模型猴制备与疾病早期诊断指标建立，参与

    5.国家杰出青年科学基金，82125008，孤独症谱系障碍与非人灵长类模型，2022-2026，400万，主持

    五、获奖情况

    1. 获得云南省自然科学一等奖1项（2018，排名第三）
    2. 入选2017年度“中国生命科学十大进展”
    3. 中国实验动物学会优秀青年人才（2018）
    4. 2021年获云南省自然科学奖一等奖（排名第四）
    5. 2021年获全国专业技术人才先进集体

    六、专利申请

    1. 陈永昌，牛昱宇，周引，卓艳，陈兴龙. 一种外埠实验用动物转移和实验笼. ZL201720614007.1. 2018.

    2. 张波，陈永昌，周引，季维智，牛昱宇. 一种用于灵长类动物的行为测试笼. ZL201820543551.6. 2019.

    3. 张波，周智刚，陈永昌，季维智. 一种用于灵长类动物眼动测试的非侵入式头部固定装置. ZL201721107312.8. 2019.

    七、入选创新团队情况

    1. 云南省高校神经疾病灵长类动物模型的创建及转化研究科技创新团队（2019-2022），带头人
    2. 云南中科灵长类生物医学重点实验室神经疾病非人灵长类模型临床前研究省创新团队（2019-2022），带头人

    八、学术兼职

    中国生物工程学会常务理事、中国研究型医院学会神经科学专业委员会副主委、《Animal Models and Experimental Medicine》及《中国比较医学杂志》副主编、《Zoological Research》编委。

    九、已发表文章 Selected Publications (# co-first or * co-correspondence)

    1. Gong Y, Bai B, Sun N, Ci B, Shao H, ZhangT, Yao H, Zhang Y, Niu Y, Liu L, Zhao H, Wu H, Zhang L, Wang T, Li S, Wei Y, Yu Y, Ribeiro Orsi AE, Liu B, Ji W, Wu J, Chen Y, Tan T. Ex utero monkey embryogenesis from blastocyst to early organogenesis. Cell. 2023 May 11;186(10):2092-2110.e23.
    2. Ren S, Huang M, Bai R, Chen L, Yang J,Zhang J, Guo W, Ji W, Chen Y. Efficient Modulation of Exon Skipping via Antisense Circular RNAs. Research (Wash D C). 2023;6:0045.
    3. Wu R, Bai B, Li F, Bai R, Zhuo Y, Zhu Z,Jia R, Li S, Chen Y, Lan X. Phenotypes and genetic etiology of spontaneous polycystic kidney and liver disease in cynomolgus monkey. Front Vet Sci. 2023 Feb 16;10:1106016.
    4. Liu Y, Shan L, Liu T, Li J, Chen Y,Sun C, Yang C, Bian X, Niu Y, Zhang C, Xi J, Rao Y. Molecular and cellular mechanisms of the first social relationship: A conserved role of 5-HT from mice to monkeys, upstream of oxytocin. Neuron. 2023 May 3;111(9):1468-1485.e7.
    5. Lu S, Chen Y, Wang Z. Advances in the pathogenesis of Rett syndrome using cell models. Animal Model Exp Med. 2022Dec;5(6):532-541.
    6. Xiao P, Bai R, Zhang T, Wu R, Chen L, HouY, Shen B, Niu Y, Li S, Ji W, Chen Y. Extensive humoral immune response to AAVs and Cas proteins in nonhuman primates. Sci Bull (Beijing). 2021 Oct 30;66(20):2061-2064.
    7. Peng Li#，Yongchang Chen*. Progress in Modeling Neural Tube Development and Defects by Organoid Reconstruction. Neurosci. Bull. 2022.6. 2022 Jun 26. doi: 10.1007/s12264-022-00896-9. [IF: 5.271]
    8. Huang M#，Li P#， Yang J#, Yongchang Chen*. Embryo-Engineered Nonhuman Primate Models: Progress and Gap to Translational Medicine.Research.2021 Aug 21
    9. Wang J#, Wang Z#, Zhang H#, Feng S#, Lu Y#, Wang S, Wang H, Sun YE, Yongchang Chen*.White Matter Structural and Network Topological Changes Underlying the Behavioral Phenotype of MECP2 Mutant Monkeys.Cerebral Cortex.2021 Jun 12.[IF: 5.357]
    10. Ran Yang, Alexander Goedel, Yu Kang, Chenyang Si, Chu Chu, Yi Zheng, Zhenzhen Chen, Peter J. Gruber, Yao Xiao, Chikai Zhou, Nevin Witman, Elif Eroglu, Chuen-Yan Leung, Yongchang Chen, Jianping Fu, Weizhi Ji*, Fredrik Lanner*, Yuyu Niu* & Kenneth R. Chien*.Amnion signals are essential for mesoderm formation in primates.Nature Communications.26 August 2021.12: 5126 (2021)
    11. 周勤,王爽,张婷,李善刚,陈永昌*. 小鼠及猕猴胚胎MECP2基因T158M单碱基突变体系的建立 *[J]. 中国生物工程杂志, 2020, 40(6): 31-39.
    12. Dong-Dong Qin , Shu-Fei Feng , Fei-Yu Zhang , Na Wang , Wen-Jie Sun , Yin Zhou , Teng-Fang Xiong , Xian-Lai Xu , Xiao-Ting Yang , Xiang Zhang , Xue Zhu , Xin-Tian Hu , Lei Xiong , Yun Liu , Yong-Chang Chen*. Potential use of actigraphy to measure sleep in monkeys: comparison with behavioral analysis from videography. Zool Res. 2020;41(4):437-443. doi:10.24272/j.issn.2095-8137.2020.056
    13. Lei Shi†, Xin Luo, Jin Jiang, Yongchang Chen, Cirong Liu, TingHu, Min Li, Qiang Lin, Yanjiao Li, Jun Huang, Hong Wang，Yuyu Niu, Yundi Shi, Martin Styner, Jianhong Wang, Yi Lu, Xuejin Sun, Hualin Yu, Weizhi Ji*,Bing Su*. Natl Sci Rev. 2019 May; 6(3): 480-493.
    14. Shuang Wang, Shuaiwei Ren, Raoxian Bai, Puhao Xiao, Qin Zhou, Yin Zhou, Zhigang Zhou, Yuyu Niu, Weizhi Ji, Yongchang Chen. No off-target mutations in functional genome regions of a CRISPR/Cas9-generated monkey model of muscular dystrophy. J Biol Chem.2018 Jul 27;293(30):11654-11658.
    15. Shuang Wang, Lichuan Yang, Raoxian Bai, Shuaiwei Ren, Yuyu Niu, Yuanye Ma, Weizhi Ji, Yongchang Chen*. Interaction of p53 and ASPPs Regulates Rhesus Monkey Embryonic Stem Cells Conversion to Neural Fate Concomitant with Apoptosis. Cell Cycle. 2018;17(9):1146-1153.
    16. Yiqiang Cui, Yuyu Niu, Jiankui Zhou, Yongchang Chen, Yiwei Cheng, Shangang Li, Zongyong Ai, Chu Chu, Hong Wang, Bo Zheng, Xuejin Chen, Jiahao Sha, Xuejiang Guo*, Xingxu Huang* Weizhi Ji*. Generation of a precise Oct4-hrGFP knockin Cynomolgus monkey model via CRISPR/Cas9-assisted homologous recombination. Cell Res. 2018 Jan; 28(3):383–386.
    17. Yan Zhuo, Shuqing Feng, Shaoyong Huang, Xinglong Chen, Yu Kang, Chenyang Si, Zifan Li, Yin Zhou, Ling Zhou, Ting Zhang, Weizhi Ji, Yuyu Niu, Yongchang Chen. Transabdominal Ultrasound-guided Multifetal Pregnancy Reduction in 10 Cases of Monkeys.Biol Reprod. 2017 Nov 1;97(5):758-761.
    18. Yongchang Chen, Juehua Yu, Yuyu Niu, Dongdong Qin, Hailiang Liu, Gang Li, Yingzhou Hu, Jiaojian Wang, Yi Lu, Yu Kang, Yong Jiang, Kunhua Wu, Siguang Li, Jingkuan Wei, Jing He, Junbang Wang, Xiaojing Liu, Yuping Luo, Chenyang Si, Raoxian Bai, Kunshan Zhang, Jie Liu, Shaoyong Huang, Zhenzhen Chen, Shuang Wang, Xiaoying Chen, Xinhua Bao, Qingping Zhang, Fuxing Li, Rui Geng, Aibin Liang, Dinggang Shen, Tianzi Jiang, Xintian Hu, Yuanye Ma, Weizhi Ji*, Yi Eve Sun*. Modeling Rett Syndrome using TALEN-edited MECP2 Mutant Monkeys. Cell. 2017 May 18;169 (5):945-955.e10.
    19. Fei Gao, Yuyu Niu, Yi Eve Sun, Hanlin Lu, Yongchang Chen, Siguang Li, Yu Kang, Yuping Luo, Chenyang Si, Juehua Yu, Chang Li, Nianqin Sun, Wei Si, Hong Wang, Weizhi Ji* & Tao Tan *. De Novo DNA Methylation during Monkey Pre-implantation Embryogenesis. Cell Res. 2017 Apr;27(4):526-539.
    20. Yongchang Chen, Yuyu Niu*, Weizhi Ji*. Genome Editing in Non-human Primates: Approach to GeneratingHuman Diseases Models. J Intern Med. 2016 Sep;280(3):246-51.
    21. Yu Kang, Bo Zheng, Bin Shen, Yongchang Chen, Lei Wang, Jianying Wang, Yuyu Niu, Yiqiang Cui, Jiankui Zhou, Hong Wang, Xuejiang Guo, Bian Hu, Qi Zhou, Jiahao Sha*, Weizhi Ji*, Xingxu Huang*. CRISPR/Cas9-mediated Dax1 Knockout in the Monkey Recapitulates Human AHC-HH. Hum Mol Genet. 2015 Dec20;24(25):7255-64.
    22. Yongchang Chen, Yuyu Niu, Yanjiao Li, Zongyong Ai, Yu Kang, Hong Shi, Zheng Xiang, Zhaohui Yang, Tao Tan, Wei Si, Wei Li, Xueshan Xia, Qi Zhou*, Weizhi Ji*, Tianqing Li* Generation of Cynomolgus Monkey Chimeric Fetuses Using Embryonic Stem Cells. Cell Stem Cell. 2015 Jul 2;17(1):116-24.
    23. Yongchang Chen, Yinghui Zheng, Yu Kang, Weili Yang, Yuyu Niu, Xiangyu Guo, Zhuchi Tu, Chenyang Si, Hong Wang, Ruxiao Xing, Xiuqiong Pu, Shang-Hsun Yang, Shihua Li, Weizhi Ji*, Xiao-Jiang Li*. Functional Disruption of the Dystrophin Gene in Rhesus Monkey Using CRISPR/ Cas9. Hum Mol Genet. 2015; 24(13):3764-3774.
    24. Yongchang Chen, Yiqiang Cui, Bin Shen, Yuyu Niu, Xiaoyang Zhao, Lei Wang, Jianying Wang, Wei Li, Qi Zhou, Weizhi Ji*, Jiahao Sha*, Xingxu Huang*. Germline Acquisition of Cas9/RNA-mediated Gene Modifications in Monkeys. Cell Res. 2015 Feb;25(2):262-5.
    25. Yuyu Niu, Xiangyu Guo, Yongchang Chen, Chuan-En Wang, Jinquan Gao, Weili Yang, Yu Kang, Wei Si, Hong Wang, Shang-Hsun Yang, Shihua Li, Weizhi Ji*, Xiao-Jiang Li*. Early Parkinson's disease Symptoms in α-synuclein Transgenic Monkeys. Hum Mol Genet. 2015 Apr15;24(8):2308-17.
    26. Hailiang Liu #, Yongchang Chen #, Yuyu Niu #, Kunshan Zhang #, Yu Kang, Weihong Ge, Xiaojing Liu, Enfeng Zhao, Chencheng Wang, Shaoyun Lin, Bo Jing, Chenyang Si, Quan Lin, Xiaoying Chen, Haijun Lin, Xiuqiong Pu, Yingying Wang, Binlian Qin, Fang Wang, Hong Wang, Wei Si, Jing Zhou, Tao Tan, Tianqing Li, Shaohui Ji, Zhigang Xue, Yuping Luo, Liming Cheng, Qi Zhou, Siguang Li*, Yi Eve Sun*, Weizhi Ji*. TALEN-mediated Gene Mutagenesis in Rhesus and Cynomolgus Monkeys. Cell Stem Cell. 2014 Mar 6; 14(3):323-8.
    27. Yuyu Niu, Bin Shen, Yiqiang Cui, Yongchang Chen, Jianying Wang, Lei Wang, Yu Kang, Xiaoyang Zhao, Wei Si, Wei Li, Andy Peng Xiang, Jiankui Zhou, Xuejiang Guo, Ye Bi, Chenyang Si, Bian Hu, Guoying Dong, Hong Wang, Zuomin Zhou, Tianqing Li, Tao Tan, Xiuqiong Pu, Fang Wang, Shaohui Ji, Qi Zhou, Xingxu Huang*, Weizhi Ji*, Jiahao Sha*. Generation of Gene-modified Cynomolgus Monkey Via Cas9/RNA-mediated Gene Targeting in One-cell Embryos. Cell. 2014 Feb 13;156(4):836-43.
    28. Huan Liu, Bo Zhao, Yongchang Chen, Dewen You, Rui Liu, Mingqiang Rong, Weizhi Ji, Ping Zheng, Ren LaiHuan Liu, Bo Zhao, Yongchang Chen, Dewen You, Rui Liu, Mingqiang Rong, Weizhi Ji*, Ping Zheng, Ren Lai*. Multiple Coagulation Factor Deficiency Protein 2 Contains the Ability to Support Stem Cell Self-renewal. FASEB J. 2013 Aug;27(8):3298-305.
    29. Yongchang Chen, Yuyu Niu, Shihua Yang, Xiechao He, Shaohui Ji, Wei Si, Xianghui Tang, Yunhua Xie, Hong Wang, Yongqing Lu, Qi Zhou, Weizhi Ji*.The Available Time Window for Embryo Transfer in The Rhesus Monkey (Macaca mulatta). Am J Primatol. 2012 Feb;74(2):165-73.
    30. Yongchang Chen, Zhengbo Wang, Yunhua Xie, Xiangyu Guo, Xianghui Tang, Shufen Wang, Shihua Yang, Kai Chen, Yuyu Niu, Weizhi Ji*. Folic Acid Deficiency Inhibits Neural Rosette Formation and Neuronal Differentiation from Rhesus MonkeyEmbryonic Stem Cells. J Neurosci Res. 2012Jul;90(7):1382-91.
    31. Yongchang Chen, Yuyu Niu*, Weizhi Ji*. Transgenic Nonhuman Primate Models for Human Diseases: Approaches and Contributing Factors. J Genet Genomics. 2012 Jun20;39(6):247-51.

    论文网 站 ( 动 态 更 新 )： https://www.researchgate.net/profile/Yongchang_Chen7

    本团队常年招收副研究员、博士生、硕士生、博士后和外国留学生，欢迎联系chenyc@lpbr.cn。

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