朱永群

2007年-2010年，北京生命科學研究所博士后

2010年-2012年，美國斯隆-凱特琳癌症研究中心/霍華德-休斯醫學研究所博士后

2012年-至今，浙江大學生命科學研究院教授，研究員，博士生導師

研究方向

我們研究組以結構生物學、生物化學為主要研究手段，並結合細胞生物學的實驗方法，研究致病菌侵染宿主細胞和人類癌症發生的分子機制。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菌等為主要研究對象，革蘭氏陰性致病菌通過特殊的分泌系統將毒性蛋白（又稱效應蛋白）分泌到人宿主細胞中，分泌的效應蛋白作用於宿主細胞內特異的關鍵分子，從而調節宿主細胞的信號通路，從而達到有利於致病菌的侵染與繁殖的目的。因此，效應蛋白在致病菌致病過程中扮演著關鍵的角色。對效應蛋白及其作用機制進行深入的研究，將會促進人們對病原菌致病機理的了解，並且有可能為治療相關傳染疾病提供線索。另一個方面，我們也對由基因組不穩定性誘發的人類癌症發生的分子機制感興趣。當基因組DNA遭受由環境和化學因素引發的損傷時，細胞將啟動DNA損傷反應機制，包括激活DNA damage checkpoint信號通路、停止細胞分裂、解開核小體的結構和募集下游DNA修復蛋白，從而對損傷的DNA進行識別與修復。DNA損傷反應機制的任何功能缺陷將會引起基因組的不穩定性，從而導致癌症的發生。我們將研究DNA損傷與修復過程中核小體的去組裝與再組裝過程以及DNA修復蛋白如何識別和修復損傷的DNA的分子機制，這將幫助我們找到相關癌症發生的原因。我們期望通過我們的研究能夠促進人們對威脅人類健康的兩大威脅-傳染性疾病與癌症的認識，並為相關的臨床治療提供寶貴的知識積累。

2021年8月16日，入選2021年第十四屆“談家楨生命科學獎”候選名單。

期刊論文

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.

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.

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.

Yan Zhou,Yongqun Zhu. Diversity of bacterial manipulation of the host ubiquitin pathways.Cellular Microbiology. 2015 Jan;17(1):26-34.

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.

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.

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.

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

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)

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.

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.

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.

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, 899–913, Dec 14, 2007.

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. 63:1127–1131, 2006.

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 1.7Å Resolution: The First Structure of a New Sequence Family of TIM Barrels.PROTEINS.58:764–768, 2005. (* equal contribution)

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)

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. 

學術成果

2013年 冷泉港-亞洲國際學術會議(Bacterial Infection and Host Defense)，蘇州

Talk title: Structural Insights into Shigella Interaction with the Host.

2013年 全球華人生物學家大會，西安

Talk title: Molecular Mechanism of Ubc13 Deamidation by OspI and the Convergence ofBacterialand Host E2 Recognition.

2012年 冷泉港-亞洲國際學術會議(Small GTPases), 蘇州

Talk title: Distinct Bacterial TBC-like GAPs Link Arf GTPase to Rab1 Inactivation to CounteractHost Defenses.

2012年 中國晶體學大會，西安

Talk title: Molecular Mechanism of Bacterial Pathogen-Host Interaction.

2008年 中國結構生物學大會，黃山

Talk title: Structure of a Shigella effector reveals a new class of ubiquitin ligases.

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