朱永群

朱永群 博士

详细介绍：

研究方向：

我们研究组以结构生物学为主要研究手段，并结合生物化学、细胞生物学等实验方法，研究致病菌与宿主细胞相互作用以及基因组稳定性维持的 分子机制。我们以革兰氏阴性致病菌如痢疾杆菌、致病性大肠杆菌和军团菌等为主要研究对象，革兰氏阴性致病菌通过特殊的分泌系统将毒性蛋白（又称效应蛋白） 分泌到人宿主细胞中，分泌的效应蛋白作用于宿主细胞内特异的关键分子，从而调节宿主细胞的信号通路，从而达到有利于致病菌的侵染与繁殖的目的。因此，效应 蛋白在致病菌致病过程中扮演着关键的角色。对效应蛋白及其作用机制进行深入的研究，将会促进人们对病原菌致病机理的了解，并且有可能为治疗相关传染疾病提 供线索。另一个方面，我们也对细胞如何维持基因组稳定性、以及由基因组不稳定性诱发的人类癌症发生的分子机制感兴趣。当基因组DNA遭受由环境和化学因素 引发的损伤时，细胞将启动DNA损伤反应机制，激活DNA damage checkpoint信号通路，停止细胞分裂，以及解开核小体的结构和募集下游DNA修复蛋白，对损伤的DNA进行识别与修复。DNA损伤反应机制的任何 功能缺陷将会引起基因组的不稳定性，从而导致癌症的发生。我们将研究DNA损伤与修复过程中核小体的变化过程以及DNA修复蛋白识别和修复损伤的DNA的 分子机制，这将帮助我们找到相关癌症发生的原因。我们期望通过我们的研究能够促进人们对威胁人类健康的两大威胁-传染性疾病与癌症的认识，并为相关的临床 治疗提供宝贵的知识积累。

Research interests:
Our research interest is to take combinatory approaches of structural biology, biochemistry and cell biology to study the molecular mechanisms underlying the bacterial pathogen-host interactions and human genome stability maintenance. Gram-negative bacterial pathogens such as Shigella flexneri, Enteropathogenic E.coli, and Legionella pneumophila deliver virulent proteins (also named effectors) into host cells through specialized secretion systems. The injected effectors target host key molecules to modulate host cellular processes for bacterial pathogen’s infection and multiplication, which plays a central role in disease pathogenesis. We are interested in functional and structural characterization of bacterial effectors and effector-target complexes that are critical for the deep and mechanistic understanding of bacterial virulence. In the second direction, we are interested in studying how cells maintain the genome stability and how genome instability induces human tumorigenesis. Genomic DNA is under constant attacks by the environmental and chemical factors. Cells employ the precise DNA damage response pathways to activate DNA damage checkpoint to stop the cell cycle, and regulate nucleosome disassembly for recruiting the downstream DNA repair complexes that recognize and repair the damaged DNAs. Defects in DNA damage response can cause genome instability, which induces many human cancers. We will study how nucleosomes are regulated in DNA damage response and how the repair complexes recognize and repair damaged DNAs, which can provide direct insights into molecular basis of the related human cancers. We hope our studies in these two research directions could extend our understanding and provide clues for clinic therapies of bacterial infectious diseases and cancer – two global threats to our human health.

Publication:

1. 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.

2. 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. 

3. 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.

4. 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.

5. 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.

6. 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)

7. De-Yu Zhu, Yong-Qun Zhu*, Ye Xiang and Da-Cheng Wang. Optimizing Protein Crystal Growth through Dynamic Seeding. Acta Cryst. (2005). D61, 772-775. (*equal contribution)

8. 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.