首页 全所PI名录
    个人简介:
  •   1981.9-1985.7:浙江大学(原杭州大学)生物系,学士;1985.9-1989.8:中国科学院遗传所,硕士;1989.9-1993.3:德国马普分子遗传学研究所,博士;1993.3-1994.7:德国马普分子遗传学研究所,博士后;1994.8-1995.9:新加坡国立大学生命科学中心,实验室主任;1995.1-2001.7:美国哥伦比亚大学遗传发育系/医学系,博士后;2001年8月起任上海生化与细胞所研究员,2001.8-2006.7:任中国科学院与德国马普学会合作项目青年科学家小组组长,2017年3月起兼任复旦大学生物医学研究院执行院长。目前担任 Development 期刊编辑顾问,J.Biol.Chem. 和 National Science Review 期刊编委,生物化学与分子生物学会常务理事;上海科技大学兼职教授。

    社会任职:
    研究方向:
  • 表观遗传调控及其与癌症等重大疾病的关系
    研究工作:
  • 多细胞生物的个体发育是一个复杂而奇妙的过程,从最原始的一个受精卵细胞发育成由不同细胞类型组成的个体,体现出细胞在时间与空间上的多样性。而这些不同细胞类型的大部分基因序列并没有改变,那么各种基因是如何实现时间空间上的表达调控等问题成为了后基因组学时代重大的科学研究问题。

    以染色质共价修饰为主要标志的表观遗传学(epigenetics),基于其不改变基因序列而引起可遗传的基因转录调控理论,为解决这一科学问题提供了一个新的研究方向。染色质共价修饰有二个方面:一是针对DNA本身的修饰,研究比较成熟的是胞嘧啶碱基第5位碳原子上的甲基化以及羟甲基化;二是对组蛋白的修饰。这两种修饰都会引起染色质结构和基因转录活性的变化。因而形成了一套相对于基本遗传学基因水平的表观遗传系统。

    在这个系统中,不仅涉及到基因如何响应内外环境的变化从而实现在时间和空间上的表达调控,而且众多癌症与重大疾病都与之息息相关。表观遗传网络也作为整合细胞内外环境因素与基因组遗传信息的媒介,直接调控了基因表达,决定了细胞增殖、分化与功能特化,在正常的生命活动中起到不可或缺的作用。特别是一些与个体发育和癌症密切相关的基因,经常发生启动子区域非正常甲基化以及组蛋白修饰的紊乱而引起疾病的发生。

    表观遗传学研究因其作用广泛、影响深远,已经引起了越来越多的重视并成为目前生命科学研究中发展迅速而崭新的研究领域。

    本实验室采用生物化学、细胞生物学和遗传学(包括基因组学)相互依托的实验手段致力于探索:DNA甲基化谱式是如何在胚胎发育早期建立起来的?异常的表观因子会对生殖细胞的发生和早期胚胎的发育产生何种影响?是否存在不依赖于TET和TDG的主动去甲基化?是否存在新的碱基修饰形式?胚胎干细胞与成体干细胞自我更新与分化是如何达到平衡的,以及哪些因素导致了这一平衡的改变而导致肿瘤和疾病发生?对表观遗传信息调控的研究将有助于了解生长发育与疾病发生发展的分子机理,为维护人类健康尤其是再生医学的技术开发提供理论依据。除了对DNA甲基化和氧化的机制感兴趣外,我们还在拓展研究范围,包括建立永生化的精子细胞系,通过囊胚补偿实现器官再生,以及真核生物对磁场的响应机制等方向。

    承担科研项目情况:
    代表论著:
  • 所有论著:http://xgl-lab.sibcb.ac.cn/xgl-lab/publications.jsp?year=all

    1. Zhang, X. J., Han, B. B., Shao, Z. Y., Yan, R., Gao, J., Liu, T., Jin, Z. Y., Lai, W., Xu, Z. M., Wang, C. H., Zhang, F., Gu, C., Wang, Y., Wang, H., Walsh, C. P., Guo, F., Xu, G. L. & Du, Y. R. Auto-suppression of Tet dioxygenases protects the mouse oocyte genome from oxidative demethylation. Nat Struct Mol Biol 31, 42-53, doi:10.1038/s41594-023-01125-1 (2024).
    2. Chen, H., Yang, Q. L., Xu, J. X., Deng, X., Zhang, Y. J., Liu, T., Rots, M. G., Xu, G. L. & Huang, K. Y. Efficient methods for multiple types of precise gene-editing in Chlamydomonas. Plant J 115, 846-865, doi:10.1111/tpj.16265 (2023).
    3. Bin Chen, Ya-Rui Du, Hong Zhu, Mei-Ling Sun, Chao Wang, Yi Cheng, Haiyan Pang, Guolian Ding, Juan Gao, Yajing Tan, Xiaomei Tong, Pingping Lv, Feng Zhou, Qitao Zhan, Zhi-Mei Xu, Li Wang, Donghao Luo, Yinghui Ye, Li Jin, Songying Zhang, Yimin Zhu, Xiaona Lin, Yanting Wu, Luyang Jin, Yin Zhou, Caochong Yan, Jianzhong Sheng, Peter R. Flatt, Guo-Liang Xu* & Hefeng Huang*. ”Maternal inheritance of glucose intolerance via oocyte TET3 insufficiency”. Nature. 2022.605, 761-766.
    4. Qin Xu, Chao Wang, Jia-Xin Zhou, Zhi-Mei Xu, Juan Gao, Peng-Fei Sui, Colum P Walsh, Hong-Bin Ji* & Guo-Liang Xu*. "Loss of TET reprograms Wnt signaling through impaired demethylation to promote lung cancer development". PNAS.  2022-02-02;119(6)
    5. Xu GL, Bochtler M. "Reversal of nucleobase methylation by dioxygenases". Nat Chem Biol.  2020-11-16;16(11):1160-1169
    6. Jian-Huang Xue, Guo-Dong Chen, Fuhua Hao, Hui Chen, Zhaoyuan Fang, Fang-Fang Chen, Bo Pang, Qing-Lin Yang, Xinben Wei, Qiang-Qiang Fan, Changpeng Xin, Jiaohong Zhao, Xuan Deng, Bang-An Wang, Xiao-Jie Zhang, Yueying Chu, Hui Tang, Huiyong Yin, Weimin Ma, Luonan Chen, Jianping Ding, Elmar Weinhold, Rahul M Kohli, Wen Liu, Zheng-Jiang Zhu, Kaiyao Huang*, Huiru Tang* & Guo-Liang Xu*. (2019). A vitamin C-derived DNA modification catalyzed by an algal TET homolog. Nature 569, 581–585.
    7. Hai-Qiang Dai, Bang-An Wang, Lu Yang, Jia-Jia Chen, Guo-Chun Zhu, Mei-Ling Sun, Hao Ge, Rui Wang, Deborah L. Chapman, Fuchou Tang, Xin Sun*, Guo-Liang Xu*. (2016). TET-mediated DNA demethylation controls gastrulation by regulating Lefty-Nodal signalling. Nature 538, 528-532.
    8. Fan Guo, Xianlong Li, Dan Liang, Tong Li, Ping Zhu, Hongshan Guo, Xinglong Wu, Lu Wen, Tian-Peng Gu, Colum P.Walsh, Jinsong Li*, Fuchou Tang*, Guo-Liang Xu*.(2014). Active and Passive Demethylation of Male and Female Pronuclear DNA in the Mammalian Zygote. Cell Stem Cell 15, 477-458.
    9. Xiao Hu, Lei Zhang, Shi-Qing Mao, Zheng Li, Jiekai Chen, Run-Rui Zhang, Hai-Ping Wu, Juan Gao, Fan Guo, Wei Liu, Gui-Fang Xu, Hai-Qiang Dai, Yujiang Geno Shi, Xianlong Li, Boqiang Hu, Fuchou Tang, Duanqing Pei, Guo-Liang Xu. (2014). Tet and TDG Mediate DNA Demethylation Essential for Mesenchymal-to-Epithelial Transition in Somatic Cell Reprogramming. Cell Stem Cell 14,512-522.
    10. Run-Rui Zhang, Qing-Yan Cui, Kiyohito Murai, Yen Ching Lim, Zachary D. Smith, Shengnan Jin, Peng Ye, Luis Rosa, Yew Kok Lee, Hai-Ping Wu, Wei Liu, Zhi-Mei Xu, Lu Yang, Yu-Qiang Ding, Fuchou Tang, Alexander Meissner, Chunming Ding*, Yanhong Shi*, Guo-Liang Xu*. (2013) Tet1 Regulates Adult Hippocampal Neurogenesis and Cognition. Cell Stem Cell 13, 237-245.
    11. Jiekai Chen, Lin Guo, Lei Zhang, Haoyu Wu, Jiaqi Yang, He Liu, Xiaoshan Wang, Xiao Hu, Tianpeng Gu, Zhiwei Zhou, Jing Liu, Jiadong Liu, Hongling Wu, Shi-Qing Mao, Kunlun Mo, Yingying Li, Keyu Lai, Jing Qi, Hongjie Yao, Guangjin Pan, Guo-Liang Xu*, Duanqing Pei*. (2013). Vitamin C modulates Tet1 function during somatic cell reprogramming. Nature Genetics, 45,1504-1509.
    12. Hui Yang, Linyu Shi, Bang-An Wang, Dan Liang, Cuiqing Zhong, Wei Liu, Yongzhan Nie, Jie Liu, Jing Zhao, Xiang Gao, Dangsheng Li, Guo-Liang Xu*, Jinsong Li*. (2012) Generation of Genetically Modified Mice by Oocyte Injection of Androgenetic Haploid Embryonic Stem Cells. Cell. 149,605-617.
    13. Yu-Fei He, Bin-Zhong Li, Zheng Li, Peng Liu, Yang Wang, Qingyu Tang, Jianping Ding, Yingying Jia, Zhangcheng Chen, Lin Li, Yan Sun, Xiuxue Li, Qing Dai, Chun-Xiao Song, Kangling Zhang, Chuan He, Guo-Liang Xu. (2011) Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science, 333, 1303-07.
    14. Tian-Peng Gu, Fan Guo, Hui Yang, Hai-Ping Wu, Gui-Fang Xu, Wei Liu, Zhi-Guo Xie, Linyu Shi, Xinyi He, Seung-gi Jin, Khursheed Iqbal, Yujiang Geno Shi, Zixin Deng, Piroska E. Szabó, Gerd P. Pfeifer, Jinsong Li* and Guo-Liang Xu*. (2011) The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature, 477,606-610.
    15. Jia-Lei Hu, Bo Zhou, Kang-Ling Zhang, Jin-Qiu Zhou and Guo-Liang Xu. (2009) The N-terminus of histone H3 is required for de novo DNA methylation in chromatin. PNAS 106, 22187-22192.
    16. Yuki O., Feng Q., Lin Y., Jiang Q., Li Y., Coffield V.M., Su L., Guo-Liang Xu* and Zhang Y*. (2005) hDOT1L Links Histone Methylation to Leukemogenesis. Cell 121,167-178.
    17. Bourc′his D., Guo-Liang Xu, C.-S. Lin, B. Bollman and T. H. Bestor. (2001) Dnmt3L and the establishment of maternal genomic imprints. Science 294, 2536-2539.
    18. Guo-Liang Xu, T. H. Bestor, D. Bourc′his, C.L. Hsieh, N. Tommerup, M., Bugge, X., Qu, J. J. Russo and E. Viegas-Péquignot. (1999) Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature 402, 187-191.
    19. Guo-Liang Xu and T. H. Bestor. (1997) Cytosine methylation targeted to predetermined sequences. Nature Genetics 17, 376-378.
    20. Chuang, L.S.H., Ian H.-I., Hoh H.-H., Ng H.-H., Guo-Liang Xu and Li B.F.L. (1997) Human DNA-(Cytosine-5) methyltransferase –PCNA complex as a target for p21 WAF1. Science 277, 1996-2000.
    获奖及荣誉:
    研究组成员:
  • 合影