人物經(jīng)歷
2012年-至今浙江大學(xué)生命科學(xué)研究院教授，研究員，博士生導(dǎo)師
2010年-2012年 美國斯隆-凱特琳癌癥研究中心/霍華德-休斯醫(yī)學(xué)研究所 博士后
2007年-2010年北京生命科學(xué)研究所博士后
2002年-2007年 中國科學(xué)院生物物理研究所 生物化學(xué)與分子生物學(xué) 博士
1998年-2002年 南開大學(xué) 生物物理學(xué) 學(xué)士
國家自然科學(xué)基金委重點(diǎn)項(xiàng)目負(fù)責(zé)人，英國皇家學(xué)會(huì)牛頓高級(jí)學(xué)者，國家基金委優(yōu)秀青年科學(xué)基金獲得者，浙江省杰出青年科學(xué)基金獲得者。
研究方向
我們研究組以結(jié)構(gòu)生物學(xué)、生物化學(xué)為主要研究手段，并結(jié)合細(xì)胞生物學(xué)的實(shí)驗(yàn)方法，研究致病菌侵染宿主細(xì)胞和人類癌癥發(fā)生的分子機(jī)制。我們以革蘭氏陰性致病菌如痢疾桿菌、致病性大腸桿菌和軍團(tuán)菌等為主要研究對(duì)象，革蘭氏陰性致病菌通過特殊的分泌系統(tǒng)將毒性蛋白（又稱效應(yīng)蛋白）分泌到人宿主細(xì)胞中，分泌的效應(yīng)蛋白作用于宿主細(xì)胞內(nèi)特異的關(guān)鍵分子，從而調(diào)節(jié)宿主細(xì)胞的信號(hào)通路，從而達(dá)到有利于致病菌的侵染與繁殖的目的。因此，效應(yīng)蛋白在致病菌致病過程中扮演著關(guān)鍵的角色。對(duì)效應(yīng)蛋白及其作用機(jī)制進(jìn)行深入的研究，將會(huì)促進(jìn)人們對(duì)病原菌致病機(jī)理的了解，并且有可能為治療相關(guān)傳染疾病提供線索。另一個(gè)方面，我們也對(duì)由基因組不穩(wěn)定性誘發(fā)的人類癌癥發(fā)生的分子機(jī)制感興趣。當(dāng)基因組DNA遭受由環(huán)境和化學(xué)因素引發(fā)的損傷時(shí)，細(xì)胞將啟動(dòng)DNA損傷反應(yīng)機(jī)制，包括激活DNA damage checkpoint信號(hào)通路、停止細(xì)胞分裂、解開核小體的結(jié)構(gòu)和募集下游DNA修復(fù)蛋白，從而對(duì)損傷的DNA進(jìn)行識(shí)別與修復(fù)。DNA損傷反應(yīng)機(jī)制的任何功能缺陷將會(huì)引起基因組的不穩(wěn)定性，從而導(dǎo)致癌癥的發(fā)生。我們將研究DNA損傷與修復(fù)過程中核小體的去組裝與再組裝過程以及DNA修復(fù)蛋白如何識(shí)別和修復(fù)損傷的DNA的分子機(jī)制，這將幫助我們找到相關(guān)癌癥發(fā)生的原因。我們期望通過我們的研究能夠促進(jìn)人們對(duì)威脅人類健康的兩大威脅-傳染性疾病與癌癥的認(rèn)識(shí)，并為相關(guān)的臨床治療提供寶貴的知識(shí)積累。
主要貢獻(xiàn)
期刊論文
1. Zhaofeng Yan, Meng Yin,Dandan Xu,Yongqun Zhu#, Xueming Li#. Structural insights into the secretin translocation channel in the type II secretion system.Nature Structural &Molecular Biology. 2017 Jan 9.
2. Deli Huang, Xinru Zheng, Zi-An Wang, Xin Chen, Wan-Ting He, Yingying Zhang, Jin-Gen Xu, Hang Zhao, Wenke Shi, Xin Wang,Yongqun Zhu, Jiahuai Han. MLKL channel in necroptosis is octamer formed by tetramers in a dyadic process.Mol Cell Biol. 2016 Dec 5.
3. Xiaofei Wang, Deqiang Yao, Jin-Gen Xu, A-Rong Li, Jianpo Xu, Panhan Fu, Yan Zhou,Yongqun Zhu. Structural basis of Cas3 inhibition by the bacteriophage protein AcrF3.Nature Structural &Molecular Biology. 2016 Sep;23(9):868-70.
4. Yan Zhou,Yongqun Zhu. Diversity of bacterial manipulation of the host ubiquitin pathways.Cellular Microbiology. 2015 Jan;17(1):26-34.
5. Jin-Gen Xu*, Chunfeng Huang*, Yang Z, Jin M, Fu P, Zhang N, Luo J, Li D, Liu M, Zhou Y,Yongqun Zhu.Crystal Structure of LGR4-Rspo1 Complex: Insights into the divergent mechanisms of ligand recognition by Leucine-rich G-protein-coupled receptors (LGRs).Journal of BiologicalChemistry. 2015 Jan 23;290(4):2455-65.
6. Kai Xu K, Chan YP, Bradel-Tretheway B, Akyol-Ataman Z,Yongqun Zhu, Dutta S, Yan L, Feng Y, Wang LF, Skiniotis G, Lee B, Zhou ZH, Broder CC, Aguilar HC, Nikolov DB. Crystal Structure of the Pre-fusion Nipah Virus Fusion Glycoprotein Reveals a Novel Hexamer-of-Trimers Assembly.PLoS Pathogens. 2015 Dec 8;11(12):e1005322.
7. Panhan Fu*, Xiaoqing Zhang*, Mengmeng Jin*, Li Xu, Chong Wang, Zongping Xia,Yongqun Zhu. Complex Structure of OspI and Ubc13: The Molecular Basis of Ubc13 Deamidation and Convergence of Bacterial and Host E2 Recognition.PLoS Pathogens. 2013 Apr;9(4):e1003322.
8. Qing Yu, Liyan Hu, Qing Yao,Yongqun Zhu, Na Dong, Da-Cheng Wang, Feng Shao. Structural analyses of Legionella LepB reveal a new GAP fold that catalytically mimics eukaryotic RasGAP.Cell Research. 2013 Jun;23(6):775-87
9. Na Dong,Yongqun Zhu#, Qiuhe Lu, Liyan Hu, Yuqing Zheng, Feng Shao#.Structurally Distinct Bacterial TBC-like GAPs Link Arf GTPase to Rab1 Inactivation to Counteract Host Defenses.Cell.2012 Aug 31;150(5):1029-41. (# co-corresponding author)
10.Yongqun Zhu, Liyan Hu, Yan Zhou, Qing Yao, and Feng Shao. Structural mechanism of host Rab1 activation by the bifunctional Legionella type IV effector SidM/DrrA.Proc Natl Acad Sci USA.2010 Mar 9; 107(10):4699-704.
11. Qing Yao, Jixin Cui,Yongqun Zhu, Guolun Wang, Liyan Hu, Chengzu Long, Ran Cao, Xinqi Liu, Niu Huang, She Chen, Liping Liu, and Feng Shao. A bacterial type III effector family uses the papain-like hydrolytic activity to arrest the host cell cycle.Proc Natl Acad Sci USA. 2009 Mar 10; 106(10):3716-21.
12.Yongqun Zhu, Hongtao Li, Jiayi Wang, Liyan Hu, Yan Zhou, Liping Liu, Feng Shao. Structure of a Shigella effector reveals a new class of ubiquitin ligases.Nature Structural & Molecular Biology.15(12):1302-8, Dec 2008.
13.Yongqun Zhu, Hongtao Li,Chengzu Long, Liyan Hu, Hao Xu, Liping Liu, She Chen, Da-Cheng Wang, and Feng Shao. Structural Insights into the Enzymatic Mechanism of the Pathogenic MAPK Phosphothreonine Lyase.Molecular Cell.28, 899u2013913, Dec 14, 2007.
14.Yong-Qun Zhu, De-Yu Zhu, Lei Yin, Ying Zhang, Clemens Vonrhein, and Da-Cheng Wang. Crystal Structure of Human Spermidine/Spermine N1-Acetyltransferase (hSSAT): The First Structure of a New Sequence Family of Transferase Homologous Superfamily.PROTEINS. 63:1127u20131131, 2006.
15. De-Yu Zhu,Yong-Qun Zhu*,Ren-Huai Huang, Ye Xiang, Na Yang, Hong-Xia Lu, Gen-Pei Li, Qi Jin, and Da-Cheng Wang. Crystal Structure of the Copper Homeostasis Protein (CutCm) from Shigella flexneri at 1.7? Resolution: The First Structure of a New Sequence Family of TIM Barrels.PROTEINS.58:764u2013768, 2005. (* equal contribution)
16.De-Yu Zhu,Yong-Qun Zhu*,Ye Xiang and Da-Cheng Wang. Optimizing Protein Crystal Growth through Dynamic Seeding.Acta Cryst. D(2005).61, 772-775. (*equal contribution)
17.Yong-Qun Zhu, De-Yu Zhu, Hong-Xia Lu, Na Yang, Gen-Pei Li, Da-Cheng Wang. Purification and Preliminary Crystallographic Studies of CutC, a Novel Copper Homeostasis Protein from Shigella flexneri.Protein & Peptide Letters. 12, 823-826, 2005.
學(xué)術(shù)成果
2013年 冷泉港-亞洲國際學(xué)術(shù)會(huì)議(Bacterial Infection and Host Defense)，蘇州
Talk title: Structural Insights into Shigella Interaction with the Host.
2013年 全球華人生物學(xué)家大會(huì)，西安
Talk title: Molecular Mechanism of Ubc13 Deamidation by OspI and the Convergence ofBacterialand Host E2 Recognition.
2012年 冷泉港-亞洲國際學(xué)術(shù)會(huì)議(Small GTPases), 蘇州
Talk title: Distinct Bacterial TBC-like GAPs Link Arf GTPase to Rab1 Inactivation to CounteractHost Defenses.
2012年 中國晶體學(xué)大會(huì)，西安
Talk title: Molecular Mechanism of Bacterial Pathogen-Host Interaction.
2008年 中國結(jié)構(gòu)生物學(xué)大會(huì)，黃山
Talk title: Structure of a Shigella effector reveals a new class of ubiquitin ligases.
