• 李善刚 (Shangang Li)

    博士、教授
    硕士研究生导师
    Ph.D,Professor

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    E-mail: lisg@lpbr.cn

    一、受教育及工作经历 Education and Work Experience

    1990年–1995年,山东农业大学,畜牧兽医专业,学士学位

    1995年–1998年,山东农业大学,动物繁殖学,硕士学位

    1998年–2002年,山东泰山医学院,基础医学部,讲师

    2002年–2006年,上海交通大学医学院,人体解剖与组织胚胎学,博士学位

    2006年–2008年,中国农业科学院北京畜牧兽医研究所,博士后

    2008年–2009年,德国 Ludwig Maximilian University of Munich,博士后

    2010年–2018年,上海交通大学医学院,实验动物科学部,副研究员

    2018年–至今,昆明理工大学灵长类转化医学研究院,教授

     

    1990-1995, Shandong Agricultural University, Bachelor of Animal Husbandry and Veterinary Medicine.

    1995-1998, Shandong Agricultural University, Master of Animal Breeding.

    1998-2002, Lecturer,Department of Basic Medicine, Shandong Taishan Medical College.

    2002-2006, Shanghai Jiaotong University School of Medicine, Human Anatomy and Histology, Ph.D.

    2006-2008,Postdoctoral Fellow, Beijing Institute of Animal Science and Veterinary Medicine, Chinese Academy of Agricultural Sciences.

    2008-2009,Postdoctoral Fellow,Ludwig Maximilian University of Munich, Germany.

    2010–2018,Associate Professor,Department of Laboratory Animal Science, School of Medicine, Shanghai Jiaotong University.

    2018–present, Professor,Institute of Primate Translational Medicine,Kunming University of Science and Technology.

    二、主要研究方向 Main Research Directions

    1.灵长类动物克隆技术的研究

    2.克隆技术在人类疾病模型构建中的应用

    3.遗传性疾病的基因治疗

     

    1. Research on cloning technology of primates.

    2. The application of cloning technology in the construction of human disease model.

    3. Gene therapy for hereditary diseases.

    三、科研领域描述 Description of Scientific Research

       克隆技术的核心是利用MII期卵母细胞将成体细胞经过重新编程,恢复分化全能性并重新发育成个体。基于克隆技术平台进行体细胞重编程关键因素的研究,从而提高对灵长类早期胚胎发育过程的认知,促进克隆技术的发展,利用克隆技术制作遗传背景一致的基因修饰的非人灵长类疾病模型。Cas9技术的发展极大提高了在胚胎期和成体细胞中基因进行基因编辑的可能性,探索基于rAAV介导的基因重组和单碱基基因编辑技术治疗人类遗传病的方法,促进遗传病治疗方法的临床转化。

     

       The core of cloning technology is the use of MII stage oocytes to reprogram adult cells to restore differentiation pluripotency and re-develop into individuals. Based on the cloning technology platform, the key factors of somatic reprogramming are studied to improve the understanding of the early embryonic development process of primates, promote the development of cloning technology, and use the cloning technology to produce genetically modified non-human primate disease modelwith consistent genetic background. The development of Cas9 technology has greatly improved the possibility of gene editing in embryonic and adult cells, exploring methods based on rAAV-mediated gene recombination and single-base gene editing technology for the treatment of human genetic diseases, and promoting the treatment of genetic diseases forclinical transformation.

    四、承担科研项目情况 Research Projects

    1. 国家自然科学基金委员会项目: 31960215 Cas9介导食蟹猴活体肝内遗传病基因外显子置换的研究,2020/01 - 2023/12 35万元 在研 主持。
    2. 国家重点研发计划项目:2018YFA0801403 基因编辑创制发育退行性与神经退行性疾病的猴模型及致病机制的研究,2019.11-2024.10, 2204万元 在研,骨干参与。
    3. 国家自然科学基金委员会项目:30770324, 应用基因敲除制备HPRT基因缺陷医学模型兔的研究, 2008.1 - 2010.12, 30万, 主持。
    4. 科技厅项目:11ZR1418800, 诱导性基因敲减疾病模型兔制作平台的建立, 2011.4-2014.3, 10万, 主持。

    五、代表性论文和专著 Representative papers

    1. Xiaopeng Hu#, Hu Wang#, Geng. G. Tian#, Changliang Hou#, Bo Xu, Xinyan Zhao, Yongqiang Zhao1, Qian Fang, Xinyue Li, Lin He, Xuejin Chen, Shangang Li* and Ji Wu*. Ofspring production of haploid spermatid-like cells derived from mouse female germline stem cells with chromatin condensation.Cell & Bioscience. 2022.12(1):5
    2. Qiurong Chang, LiyunYang, Yawei Gao, Lili Liu, Huiyang Wang, Li Fu, Jing Zhou, Ting Zhang, Xuejin Chen, Yao Li ,Shangang Li(*), Production of offspring by intracytoplasmic sperm injection using sperm from deceased transgenic mice at different postmortem intervals Theriogenology 2020 157:314-320.
    3. Ting Zhang, Yu Kang, Li Li, Yin Zhou, Xinglong Chen, Yan Zhuo, Zifan Li, Hong Wang, Yuyu Niu, Weizhi Ji, Shangang Li(*), Yongchang Chen, Interspecies Embryo Transfer between Rhesus and Cynomolgus Monkeys. Journal of Genetics and Genomics 2020 47:333-336
    4. Liu Lili, Cao Jianchang, Chang Qiurong, Xing Fengying, Yan Guofeng, Fu Li, Wang Huiyang, Ma Zhengwen, Chen Xuejin, Li Yao and Li Shangang(*),In vivo Exon Replacement in the Mouse Atp7b Gene by the Cas9 System. Human Gene Therapy 2019 30(9):1079-1092
    5. Jiang, Weihua; Liu, Lili; Chang, Qiurong; Xing, Fengying; Ma, Zhengwen; Fang, Zhenfu; Zhou, Jing; Fu, Li; Wang, Huiyang; Huang, Xingxu; Chen, Xuejin; Li, Yao; Li, Shangang(*), Production of Wilson Disease Model Rabbits with Homology-Directed Precision Point Mutations in the ATP7B Gene Using the CRISPR/Cas9 System. Scientific Reports, 2018.1.22, 8(1):1332 ~ 1332
    6. Yin, Mingru(#); Jiang, Weihua; Fang, Zhenfu; Kong, Pengcheng; Xing, Fengying; Li, Yao; Chen, Xuejin; Li, Shangang(*), Generation of hypoxanthine phosphoribosyltransferase gene knockout rabbits by homologous recombination and gene trapping through somatic cell nuclear transfer. Scientific Reports, 2015.11.2, 5:16023 ~ 16023
    7. Yin, Mingru; Fang, Zhenfu; Jiang, Weihua; Xing, Fengying; Jiang, Manxi; Kong, Pengcheng; Li, Yao; Zhou, Xiaomei; Tang, Lan; Li, Shangang(*); Chen, Xuejin, The Oct4 promoter-EGFP transgenic rabbit: a new model for monitoring the pluripotency of rabbit stem cells.International Journal of Developmental Biology, 2013, 57(11-12):845 ~ 852
    8. Xiaomei Zhou, Mingru Yin, Weihua Jiang, Manxi Jiang, Shangang Li*, Heping Li, Xuejin Chen*, Electrical activation of rabbit oocytes increases fertilization and embryo development by intracytoplasmic sperm injection using sperm from deceased male.Journal of Assisted Reproduction and Genetics, 2013, 30(12):1605 ~ 1610
    9. Li, Shangang; Guo, Yi; Shi, Jianjun; Yin, Chunguang; Xing, Fengying; Xu, Lingyang; Zhang, Chuanshan; Liu, Tao; Li, Yao; Li, Hongbin; Du, Lixin; Chen, Xuejin, Transgene expression of enhanced green fluorescent protein in cloned rabbits generated from in vitro-transfected adult fibroblasts. Transgenic Research, 2009.4, 18(2):227 ~ 23
    10. Li, Shangang; Chen, Xuejin; Shi, Jianjun; Guo, Yi; Yin, Chunguang; Du, Lixin; Sheng, Hui Z., Cloning rabbits from fetal fibroblasts. Livestock Science, 2009.5, 122(1):77 ~ 80
    11. Li, Shangang , Qin B-L, Li W-L, Shi Z-D, Tian Y-B, Chen X-J, Offspring from heterotopic transplantation of newborn mice ovaries. Reproduction in Domestic Animals, 2009.10, 44(5):764 ~ 770
    12. Shangang Li, Xuejin Chen, Zhenfu Fang, Jianjun Shi, Hui Z Sheng, Rabbits generated from fibroblasts through nuclear transfer. Reproduction, 2006.6, 131(6):1085 ~ 1090
    13. Zhen F.Fang, HuiGai, You Z.Huang, Li, Shangang, Xue J.Chen, Jian J.Shi, Li Wu, Ailian Liu, Ping Xu, Hui Z.Sheng, Rabbit embryonic stem cell lines derived from fertilized, parthenogenetic or somatic cell nuclear transfer embryos. Experimental Cell Research, 2006.11.1, 312(18):3669 ~ 3682
    14. Xiao Puhao, Bai Raoxian, Zhang Ting, Wu Ruo, Chen Lijiao, Hou Yu, Shen Bin, Niu Yuyu, Li Shangang, Ji Weizhi, Chen Yongchang,Extensive humoral immune response to AAVs and Cas proteins in nonhuman primates Science Bulletin, 2021, 66(20): 2061-2064.
    15. He Xiaoxiao, Wang Jiangbo, Yang Xiaona, zhang Xiuze, Huang Dan, Li Xie, zou Yejun, Chen Chiqi, Yu Zhuo, Xie Li, Zhang Yaping, Liu Ligen, Li Shangang, Zhang Yuzheng, Shao Hongfang, Yu Ye, Zhen Junke Bone marrow niche ATP levels determine leukemia-initiating cell activity via P2X7 in leukemic models Journal of Clinical Investigation, 2021, 131(4)
    16. Cui, Yiqiang(#); Niu, Yuyu; Zhou, Jiankui; Chen, Yongchang; Cheng, Yiwei; Li, Shangang; Ai, Zongyong; Chu, Chu; Wang, Hong; Zheng, Bo; Chen, Xuejin; Sha, Jiahao; Guo, Xuejiang; Huang, Xingxu; Ji, Weizhi, Generation of a precise Oct4-hrGFP knockin cynomolgus monkey model via CRISPR/Cas9-assisted homologous recombination. Cell Research, 2018.1.12
    17. Wu, Ling(#); Lu, Yan; Jiao, Yang; Liu, Bin; Li, Shangang; Li, Yao; Xing, Fengying; Chen, Dongbao; Liu, Xing; Zhao, Jiejie; Xiong, Xuelian; Gu, Yanyun; Lu, Jieli; Chen, Xuejin; Li, Xiaoying, Paternal Psychological Stress Reprograms Hepatic Gluconeogenesis in Offspring. Cell Metabolism, 2016.4.12, 23(4):735 ~ 743
    18. Pengcheng Kong, Mingru Yin, Dongbao Chen1, Shangang Li,Yao Li, Fengying Xing, Manxi Jiang, Zhenfu Fang, Qifeng Lyu,and Xuejin Chen Effects of the histone deacetylaseinhibitor ‘Scriptaid’ on thedevelopmental competence of mouseembryos generated through roundspermatid injection. Human reproduction 2017 Jan;32(1):76-87

     

    六、获奖情况

    1. 获得上海市科学技术奖二等奖1项(2011)