研究队伍
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孙 强    
孙强,1973年5月生,研究员,博士生导师。现任中国科学院神经科学研究所非人灵长类研究(苏州)平台主任,中科院脑科学与智能技术卓越创新中心成员。1996本科毕业于内蒙古哲理木畜牧学院,1999年硕士毕业于扬州大学,2002年在上海医药研究院获药理学博士学位。1999至2005年在扬州大学实验动物教研组任教,并从事实验动物和转基因大小鼠相关研究工作。2005至2009年在华东师范大学脑功能基因组学研究所从事非人灵长类生殖生理和转基因猴构建研究。2009年开始担任中科院神经科学研究所非人灵长类研究(苏州)平台主任。国家杰出青年基金获得者,荣获2018年谈家桢生命科学创新奖。
主要研究方向及内容

1、非人灵长类辅助生殖技术研究
恒河猴和食蟹猴在生殖生理上与人类高度相似,为有月经周期的单胎繁殖动物,但过长的性成熟时间(约5年)却成了这两种模式动物得以广泛应用的最大障碍。本实验室建立了高效的试管猴构建技术和基于精巢移植的精子加速成熟技术,成功将雄性食蟹猴的传代时间缩短到2.5年,并得到了健康的食蟹猴后代。我们将在深入研究猴生殖生理基础上继续优化非人灵长类辅助生殖技术,并解析生殖内分泌调控相关疾病发生机制。

2、非人灵长类模式动物构建及技术优化
本实验室已经建立基于慢病毒转染的转基因猴构建技术、基于分子剪刀的基因敲出和敲入猴构建技术和食蟹猴单倍体干细胞分离培养技术,并成功得到了世界首批体细胞克隆猴。我们将继续综合利用干细胞、病毒转染、基因编辑和体细胞克隆等技术手段开展非人灵长类模式动物构建及相关建技术的建立和优化的研究工作。

3、核质互换及线粒体相关疾病动物模型构建研究
线粒体DNA突变引起的疾病可以通过母系遗传到后代,核质置换技术是解决此类问题的唯一可靠方案。核质置换技术的安全性和有效性评估是此技术开展临床应用前的最迫切问题。我们将在非人灵长类水平研究不同核质置换技术的有效性及安全性问题,为该技术的临床应用提供重要的参考数据。在此基础上,我们还将进一步开展线粒体基因突变疾病动物模式构建及表型分析等研究工作。

4、非人灵长类模式动物表型标准化范式建立
开展针对脑疾病、脑认知、肿瘤、免疫、视觉、听觉和生殖生理及病原微生物与宿主关系等非人灵长类实验动物模型的表型分析和标准化范式建立研究。


代表性论文

Xiaozhen He#, Wenfeng Chen#, Zhen Liu#, Guirong Yu, Youbang Chen, Yi-Jun Cai, Ling Sun, Wanli Xu, Lili Zhong, Caixi Gao, Jishen Chen, Minjie Zhang, Shengxi Yang, Yizhou Yao, Zhiping Zhang, Fujun Ma, Chen-Chen Zhang, Hui-Ping Lu, Bin Yu, Tian-Lin Cheng, Juhui Qiu, Qing Sheng, Hai-Meng Zhou, Zhi-Rong Lv, Junjun Yan, Yongjian Zhou, Zilong Qiu, Zongbin Cui, Xi Zhang, Anming Meng, Qiang Sun*, Yufeng Yang*. (2020) Efficient and risk-reduced genome editing using double nicks enhanced by bacterial recombination factors in multiple species. NAR. doi: 10.1093/nar/gkaa195.

Zongyang Lu#, Zhen Liu#, Wei Mao#, Xinying Wang, Xiaoguo Zheng, Shanshan Chen, Beibei Cao, Shisheng Huang, Xuliang Zhang, Tao Zhou, Yu Zhang, Xingxu Huang*, Qiang Sun*, Jia-Da Li*.(2020) Locus-specific DNA methylation of Mecp2 promoter leads to autism-like phenotypes in mice. Cell Death Dis 11 (2), 1-11.

Jianan Li#, Zhen Liu#, Shisheng Huang#, Xiao Wang, Guanglei Li, Yuting Xu, Wenxia Yu, Shanshan Chen, Yu Zhang, Hanhui Ma, Zunfu Ke, Jia Chen*, Qiang Sun*, Xingxu Huang*. (2019) Efficient base editing in G/C-rich regions to model androgen insensitivity syndrome. Cell Res 29, 174–176.

Shisheng Huang#, Zhaodi Liao#, Xiangyang Li#, Zhen Liu,Guanglei Li,Jianan Li, Zongyang Lu,Yu Zhang, Xiajun Li, Xu Ma*, Qiang Sun*,Xingxu Huang*.(2019) Developing ABEmax-NG with Precise Targeting and Expanded Editing Scope to Model Pathogenic Splice Site Mutations In Vivo. iScience 15, 640–648.

Zhen Liu#*, Yijun Cai#, Zhaodi Liao#, Yuting Xu, Yan Wang, Zhanyang Wang,Xiaoyu Jiang, Yuzhuo Li, Yong Lu, Yanhong Nie, Xiaotong Zhang, Chunyang Li,Xinyan Bian, Mu-ming Poo, Hung-Chun Chang*, Qiang Sun*.(2019) Cloning of a Gene-edited Macaque Monkey by Somatic Cell Nuclear Transfer. National Science Review. 6:101-108

Peiyuan Qiu#, Jian Jiang#, Zhen Liu#, Yijun Cai, Tao Huang, Yan Wang,Qiming Liu, Yanhong Nie, Fang Liu, Jiumu Cheng, Qing Li, Yun-Chi Tang,Mu-ming Poo, Qiang Sun*, Hung-Chun Chang*.(2019) BMAL1 knockout macaque monkeys display reduced sleep and psychiatric disorders. National Science Review. 6:87-100

Hui Long#, Yan Wang#, Li Wang#, Yong Lu, Yanhong Nie, Yijun Cai, Zhen Liu, Miaomiao Jia, Qifeng Lyu*, Yanping Kuang*, Qiang Sun*.(2018) Age-related nomograms of serum anti-Mullerian hormone levels in female monkeys: Comparison of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) monkeys. Gen Comp Endocrinl.269:171-176

Hui Long#, Yanhong Nie#, Li Wang#, Yong Lu, Yan Wang, Yijun Cai, Zhen Liu, Miaomiao Jia, Qifeng Lyu*, Yanping Kuang* and Qiang Sun*. (2018) Serum anti-Mullerian hormone predicts ovarian response in (Macaca fascicularis) monkeys. Endocrine Connections 7: 983–989.

Tao Zhang#, Xin Jiang#, Min Xu, Haifang Wang, Xiao Sang, Meiling Qin, Puhua Bao, Ruiqi Wang, Chenchen Zhang, Huiping Lu, Yuzhuo Li, Jin Ren, Hung-Chun Chang, Jun Yan, Qiang Sun*, Jin Xu*. (2018) Sleep and circadian abnormalities precede cognitive deficits in R521C FUS knockin rats. Neurobiol. Aging 72:159-170.

Zhen Liu#, Zongyang Lu#, Guang Yang#, Shisheng Huang, Guanglei Li2, Songjie Feng, Yajing Liu, Jianan Li,Wenxia Yu, Yu Zhang, Jia Chen, Qiang Sun* & Xingxu Huang*. (2018) Efficient generation of mouse models of human diseases via ABE- and BE-mediated base editing. Nature communication, 9:2338.

Zhen Liu, Yijun Cai, Yan Wang, Yanhong Nie, Chenchen Zhang, Yuting Xu, Xiaotong Zhang, Yong Lu, Zhanyang Wang, Muming Poo, and Qiang Sun* (2018) Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer. Cell 172: 881–887.

Xuan Yao#, Zhen Liu#, Xing Wang#, Yan Wang, Yan-Hong Nie, Liang Lai, Ruilin Sun, Linyu Shi, Qiang Sun* & Hui Yang* (2018) Generation of knock-in cynomolgus monkey via CRISPR/Cas9 editing. Cell Res. 28(3):379-382.

Tian, Y. #, Yang, C. #, Shang, S. #, Cai, Y. #, Deng, X. #, Zhang, J., Shao, F., Zhu, D., Liu, Y., Chen, G., Liang, J.*, Sun, Q.*, Qiu, Z.*, and Zhang, C.* (2017) Loss of FMRP impaired hippocampal long-term plasticity and spatial learning in rats. Front. Mol. Neurosci. 10: 269.

Yao X#, Wang X#, Hu X#, Liu Z#, Liu J, Zhou H, Shen X, Wei Y, Huang Z, Ying W, Wang Y, Nie YH, Zhang CC, Li S, Cheng L, Wang Q, Wu Y, Huang P, Sun Q*, Shi L*, Yang H*. (2017) Homology-mediated end joining-based targeted integration using CRISPR/Cas9. Cell Research 27(6):801-814.

Zuo, E. #, Cai, Y. #, Li, K. #, Wei, Y. #, Wang, B. #, Sun, Y., Liu, Z., Liu, J., Hu, X., Wei, W., Huo, X., Shi, L., Tang, C., Liang, D., Wang, Y., Nie, Y., Zhang, C., Yao, X., Wang, X., Zhou, C., Ying, W., Wang, Q., Chen, R., Shen, Q., Xu, G., Li, J., Sun, Q.*, Xiong, Z.* and Yang,H.* (2017)  One-step generation of complete gene knockout mice and monkeys by CRISPR/Cas9-mediated gene editing with multiple sgRNAs. Cell Research 27:933–945.

Zhen Liu#, Xiao Li#, Jun-Tao Zhang, Yi-Jun Cai, Tian-Lin Cheng, Yan Wang, Chen-Chen Zhang, Yan-Hong Nie, Wen-Jie Bian, Ling Zhang, Jian-Qiu Xiao, Bin Lu, Yue-Fang Zhang, Xiao-Di Zhang, Xiao Sang, Jia-Jia Wu, Xiu Xu, Zhi-Qi Xiong, Feng Zhang, Xiang Yu, Neng Gong, Wen-Hao Zhou, Qiang Sun*, Zilong Qiu*. (2016) Autism-like behaviors and germline transmission of transgenic monkeys expressing human MeCP2. Nature 530:98-102.

Zhen Liu, Yan-Hong Nie, Chen-Chen Zhang, Yi-Jun Cai, Yan Wang, Hui-Ping Lu, Yu-Zhuo Li, Cheng Cheng, Zi-Long Qiu, Qiang Sun*. (2016) Generation of macaques with sperm derived from juvenile monkey testicular xenografts. Cell Research 26:139-142.

Zhen Liu#, Xue Zhou#, Ying Zhu#, Zhi-Fang Chen, Bin Yu, Yan Wang, Chen-Chen Zhang, Yan-Hong Nie, Xiao Sang, Yi-Jun Cai, Yue-Fang Zhang, Tian-Lin Cheng, Chen Zhang, Wen-Hao Zhou, Qiang Sun,* Zilong Qiu,*. (2014) Generation of a monkey with MECP2 mutations by TALEN-based gene targeting. Neurosci Bull. 30(3): 381–386.

Hui Yang#, Zhen Liu#, Yu Ma#, Cuiqing Zhong, Qi Yin, Chikai Zhou, Yijun Cai, Hanzhi Zhao, Hui Wang, Fan Tang, Yan Wang, Chenchen Zhang, Dongmei Lai, Mu-ming Poo, Dangsheng Li, Ying Jin*, Qiang Sun*, and Jinsong Li*. (2013) Generation of haploid embryonic stem cells from Macaca fascicularis monkey parthenotes. Cell Research 23:1187–1200.

Qiang Sun*, Juan Dong, Wenting Yang, Yujuan Jin, Mingying Yang, Yan Wang, Philip L. Wang, and Yinghe Hu*, and Joe Z. Tsien*. (2008) Efficient reproduction of cynomolgus monkey using pronuclear embryo transfer technique. PNAS. 105(35): p. 12956-12960.

实验室网址:http://www.cebsit.cas.cn/ggpt/yjpt/lzlyjptsz/tgjs/
E-mail: qsun@@ion.ac.cn
电话:021-54921757