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首頁(yè) 全所PI名錄
  • 徐國(guó)良
  • 研究員，中科院院士，博士生導(dǎo)師
  • E-mail: glxu@@sibcb.ac.cn
  • 實(shí)驗(yàn)室主頁(yè): https://xgl-lab.sibcb.ac.cn/
    個(gè)人簡(jiǎn)介：

  • 　　1981.9-1985.7：浙江大學(xué)(原杭州大學(xué))生物系，學(xué)士;1985.9-1989.8：中國(guó)科學(xué)院遺傳所，碩士;1989.9-1993.3：德國(guó)馬普分子遺傳學(xué)研究所，博士;1993.3-1994.7：德國(guó)馬普分子遺傳學(xué)研究所，博士后;1994.8-1995.9：新加坡國(guó)立大學(xué)生命科學(xué)中心，實(shí)驗(yàn)室主任;1995.1-2001.7：美國(guó)哥倫比亞大學(xué)遺傳發(fā)育系/醫(yī)學(xué)系，博士后;2001年8月起任上海生化與細(xì)胞所研究員，2001.8-2006.7：任中國(guó)科學(xué)院與德國(guó)馬普學(xué)會(huì)合作項(xiàng)目青年科學(xué)家小組組長(zhǎng)，2017年3月起兼任復(fù)旦大學(xué)生物醫(yī)學(xué)研究院執(zhí)行院長(zhǎng)。目前擔(dān)任 Development 期刊編輯顧問(wèn)，J.Biol.Chem. 和 National Science Review 期刊編委,生物化學(xué)與分子生物學(xué)會(huì)常務(wù)理事;上?？萍即髮W(xué)兼職教授。

    社會(huì)任職：
    研究方向：
  • 表觀遺傳調(diào)控及其與癌癥等重大疾病的關(guān)系
    研究工作：

  • 多細(xì)胞生物的個(gè)體發(fā)育是一個(gè)復(fù)雜而奇妙的過(guò)程，從最原始的一個(gè)受精卵細(xì)胞發(fā)育成由不同細(xì)胞類(lèi)型組成的個(gè)體，體現(xiàn)出細(xì)胞在時(shí)間與空間上的多樣性。而這些不同細(xì)胞類(lèi)型的大部分基因序列并沒(méi)有改變，那么各種基因是如何實(shí)現(xiàn)時(shí)間空間上的表達(dá)調(diào)控等問(wèn)題成為了后基因組學(xué)時(shí)代重大的科學(xué)研究問(wèn)題。

    以染色質(zhì)共價(jià)修飾為主要標(biāo)志的表觀遺傳學(xué)（epigenetics），基于其不改變基因序列而引起可遺傳的基因轉(zhuǎn)錄調(diào)控理論，為解決這一科學(xué)問(wèn)題提供了一個(gè)新的研究方向。染色質(zhì)共價(jià)修飾有二個(gè)方面：一是針對(duì)DNA本身的修飾，研究比較成熟的是胞嘧啶堿基第5位碳原子上的甲基化以及羥甲基化；二是對(duì)組蛋白的修飾。這兩種修飾都會(huì)引起染色質(zhì)結(jié)構(gòu)和基因轉(zhuǎn)錄活性的變化。因而形成了一套相對(duì)于基本遺傳學(xué)基因水平的表觀遺傳系統(tǒng)。

    在這個(gè)系統(tǒng)中，不僅涉及到基因如何響應(yīng)內(nèi)外環(huán)境的變化從而實(shí)現(xiàn)在時(shí)間和空間上的表達(dá)調(diào)控，而且眾多癌癥與重大疾病都與之息息相關(guān)。表觀遺傳網(wǎng)絡(luò)也作為整合細(xì)胞內(nèi)外環(huán)境因素與基因組遺傳信息的媒介，直接調(diào)控了基因表達(dá)，決定了細(xì)胞增殖、分化與功能特化，在正常的生命活動(dòng)中起到不可或缺的作用。特別是一些與個(gè)體發(fā)育和癌癥密切相關(guān)的基因，經(jīng)常發(fā)生啟動(dòng)子區(qū)域非正常甲基化以及組蛋白修飾的紊亂而引起疾病的發(fā)生。

    表觀遺傳學(xué)研究因其作用廣泛、影響深遠(yuǎn)，已經(jīng)引起了越來(lái)越多的重視并成為目前生命科學(xué)研究中發(fā)展迅速而嶄新的研究領(lǐng)域。

    本實(shí)驗(yàn)室采用生物化學(xué)、細(xì)胞生物學(xué)和遺傳學(xué)（包括基因組學(xué)）相互依托的實(shí)驗(yàn)手段致力于探索：DNA甲基化譜式是如何在胚胎發(fā)育早期建立起來(lái)的？異常的表觀因子會(huì)對(duì)生殖細(xì)胞的發(fā)生和早期胚胎的發(fā)育產(chǎn)生何種影響？是否存在不依賴(lài)于TET和TDG的主動(dòng)去甲基化？是否存在新的堿基修飾形式？胚胎干細(xì)胞與成體干細(xì)胞自我更新與分化是如何達(dá)到平衡的，以及哪些因素導(dǎo)致了這一平衡的改變而導(dǎo)致腫瘤和疾病發(fā)生？對(duì)表觀遺傳信息調(diào)控的研究將有助于了解生長(zhǎng)發(fā)育與疾病發(fā)生發(fā)展的分子機(jī)理，為維護(hù)人類(lèi)健康尤其是再生醫(yī)學(xué)的技術(shù)開(kāi)發(fā)提供理論依據(jù)。除了對(duì)DNA甲基化和氧化的機(jī)制感興趣外，我們還在拓展研究范圍，包括建立永生化的精子細(xì)胞系，通過(guò)囊胚補(bǔ)償實(shí)現(xiàn)器官再生，以及真核生物對(duì)磁場(chǎng)的響應(yīng)機(jī)制等方向。

    承擔(dān)科研項(xiàng)目情況：
    代表論著：

  • 所有論著：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.
    獲獎(jiǎng)及榮譽(yù)：
    研究組成員：

  • 合影