个人简历:
1983.09－1987.07 大连轻工业学院 学士
1987.09－1991.09 丹东鸭绿江造纸厂 助理工程师
1991.09－1994.07 石油化工科学研究院 硕士
1994.09－1997.07 协和医科大学、药物研究所 博士
1997.09－1999.08 中科院生物物理研究所 博士后
1999.09－2004.07 普林斯顿大学 博士后
2004.07－2009.03 北京生命科学研究所 研究员
2009.03－至今 清华大学生命科学学院 教授
主要科研领域及方向:
本实验室关注并研究在生物学及药学应用中的重要大分子结构与功能。主要通过蛋白晶体衍射的方法及一些细胞生物学、生物化学等手段阐述这些生物大分子在结构和功能上的联系。我们实验室并不局限于已建立的研究框架，还在与北京生命科学研究所的其他研究小组合作，开展联合研究项目。
一个正进行的研究方向将关注于组蛋白的共价修饰调控基因转录的分子机制，主要集中于组蛋白甲基化及去甲基化酶催化机理的研究。另外，一些调控蛋白如何特异性识别不同的组蛋白的共价修饰也属于我们的研究范围。我们另外的一个研究的领域是有关病原菌与宿主间的相互关系。在植物与动物体中，都编码一类高度保守的蛋白质——NBS-LRR蛋白。这类蛋白对动植物种的免疫反应都具有很重要的作用。但是目前我么对病原体激活这类蛋白从而引起免疫反应的分子机制了解的还很少。我们正试图通过结构生物学的方法结合生物化学手段重点研究这一问题。
代表论文:
1. Bunyamwera virus possesses a distinct nucleocapsid protein to facilitate genome encapsidation. Li B., Wang Q., Pan X., Fernández de Castro, I., Sun Y., Guo Y., Tao X., Risco C., Sui S.F. and Lou Z.* Proc Natl Acad Sci USA
2. Crimean-Congo hemorrhagic fever virus nucleoprotein reveals an endonuclease activity in the Bunyaviruses. Guo Y., Wang W., Ji W., Deng M., Sun Y., Zhou H., Yang C., Deng F., Wang H., Hu Z.*, Lou Z.* and Rao Z*. Proc Natl Acad Sci USA 2012 Mar 27;109(13):5046-51.
3. Structural basis of a histone H3 lysine 4 demethylase required for stem elongation in rice. Chen Q, Chen X, Wang Q, Zhang F, Lou Z*, Zhang Q*, Zhou DX*. PLoS Genet. 2013 Jan;9(1):e1003239.
4. Enterovirus 71 VPg uridylation uses a two-molecular mechanism of 3D polymerase. Sun Y., Wang Y., Shan C., Chen C., Xu P., Song M., Zhou H., Yang C., Xu W., Shi P.Y., Zhang B., Lou Z.*. J Virol. 2012 Dec;86(24):13662-71.
5. Crystal structure of EV71 RNA-dependent RNA polymerase complexed with its protein primer VPg: Implication for a trans mechanism of VPg uridylylation. Chen C., Wang Y., Shan C., Sun Y., Xu P., Zhou H., Yang C., Shi P.Y., Rao Z., Zhang B.* and Lou Z.*. J Virol.
6. Crystal Structure of 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase (IspE) from Mycobacterium tuberculosis. Shan S., Chen X., Liu T., Zhao H., Rao Z. and Lou Z.*. FASEB J. 2011 Jan 31.
7. Crystal structure of an avian influenza polymerase PA(N) reveals an endonuclease active site. Yuan P.$, Bartlam M.$, Lou Z.$, Chen S., Zhou J., He X., Lv Z., Ge R., Li X., Deng T., Fodor E., Rao Z. and Liu Y. Nature. 2009 Apr 16; 458(7240):909-13.
8. The crystal structure of porcine reproductive and respiratory syndrome virus nonstructural protein Nsp1beta reveals a novel metal-dependent nuclease. Xue F., Sun Y., Yan L., Zhao C., Chen J., Bartlam M., Li X., Lou Z.*, Rao Z. J Virol. 2010 Jul;84(13):6461-71.
9. Crystal Structure of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Leader Protease Nsp1α. Sun Y., Xue F., Guo Y., Ma M., Hao N., Zhang X.C., Lou Z.*, Li X., Rao Z. J Virol. 2009 Nov;83(21):10931-40.
1. Tang J, Han Z, Sun Y, Zhang H, Gong X, Chai J.Structural basis for recognition of an endogenous peptide by the plant receptor kinase PEPR1.Cell Res. 2015 Jan;25(1):110-20.
2. Song W, Han Z, Sun Y, Chai J.Crystal structure of a plant leucine rich repeat protein with two island domains.Sci China Life Sci. 2014 Jan;57(1):137-44.
3. Li Y, Zhang L, Liu T, Chai C, Fang Q, Wu H, Agudelo Garcia PA, Han Z, Zong S, Yu Y, Zhang X, Parthun MR, Chai J, Xu RM, Yang M.Hat2p recognizes the histone H3 tail to specify the acetylation of the newly synthesized H3/H4 heterodimer by the Hat1p/Hat2p complex.Genes Dev. 2014 Jun 1;28(11):1217-27.
4. Han Z, Sun Y, Chai J.Structural insight into the activation of plant receptor kinases.2014 Curr Opin Plant Biol. 2014 Aug;20:55-63.
5. Xu, C., Li, M., Wu, J., Guo, H., Li, Q., Zhang, Y., Chai, J., Li, T., and Xue, Y. (2013). Identification of a canonical SCF(SLF) complex involved in S-RNase-based self-incompatibility of Pyrus (Rosaceae). Plant Mol Biol 81, 245-257.
6. Sun Y, Han Z, Tang J, Hu Z, Chai C, Zhou B, Chai J.Structure reveals that BAK1 as a co-receptor recognizes the BRI1-bound brassinolide.Cell Res. 2013 Nov;23(11):1326-9.
7. Sun Y, Li L, Macho AP, Han Z, Hu Z, Zipfel C, Zhou JM, Chai J.Structural basis for flg22-induced activation of the Arabidopsis FLS2-BAK1 immune complex.Science. 2013 Nov 1;342(6158):624-8.
8. She J, Han Z, Zhou B, Chai J.Structural basis for differential recognition of brassinolide by its receptors.Protein Cell. 2013 Jun;4(6):475-82.
9. Hu Z, Yan C, Liu P, Huang Z, Ma R, Zhang C, Wang R, Zhang Y, Martinon F, Miao D, Deng H, Wang J, Chang J, Chai J.Crystal structure of NLRC4 reveals its autoinhibition mechanism.Science. 2013 Jul 12;341(6142):172-5.
10. Chai C, Yu Y, Zhuo W, Zhao H, Li X, Wang N, Chai J, Yang M.Structural basis for a homodimeric ATPase subunit of an ECF transporter.Protein Cell. 2013 Oct;4(10):793-801.
11. Hao W, Collier SM, Moffett P, Chai J.Structural basis for the interaction between the potato virus X resistance protein (Rx) and its cofactor Ran GTPase-activating protein 2 (RanGAP2).J Biol Chem. 2013 Dec 13;288(50):35868-76.
12. Liu, P., Hu, Z., Zhou, B., Liu, S., and Chai, J. (2013). Crystal structure of an LRR protein with two solenoids. Cell Res.
13. Yang, H., Han, Z., Cao, Y., Fan, D., Li, H., Mo, H., Feng, Y., Liu, L., Wang, Z., Yue, Y., Chai, J.,et al. (2012). A companion cell-dominant and developmentally regulated H3K4 demethylase controls flowering time in Arabidopsis via the repression of FLC expression. PLoS Genet 8, e1002664.
14. Yuan, W., Wu, T., Fu, H., Dai, C., Wu, H., Liu, N., Li, X., Xu, M., Zhang, Z., Niu, T., et al. Chai, J. (2012). Dense chromatin activates Polycomb repressive complex 2 to regulate H3 lysine 27 methylation. Science 337, 971-975.
15. Liu, T., Liu, Z., Song, C., Hu, Y., Han, Z., She, J., Fan, F., Wang, J., Jin, C., Chang, J., et al. Chai, J. (2012). Chitin-induced dimerization activates a plant immune receptor. Science 336, 1160-1164.
16. Gao, H., Wu, X., Chai, J., and Han, Z. (2012). Crystal structure of a TALE protein reveals an extended N-terminal DNA binding region. Cell Res 22, 1716-1720.
17. Cheng, W., Yin, K., Lu, D., Li, B., Zhu, D., Chen, Y., Zhang, H., Xu, S., Chai, J., and Gu, L. (2012). Structural insights into a unique Legionella pneumophila effector LidA recognizing both GDP and GTP bound Rab1 in their active state. PLoS Pathog 8, e1002528.
18. Bai, S., Liu, J., Chang, C., Zhang, L., Maekawa, T., Wang, Q., Xiao, W., Liu, Y., Chai, J., Takken, F. L., et al. (2012). Structure-function analysis of barley NLR immune receptor MLA10 reveals its cell compartment specific activity in cell death and disease resistance. PLoS Pathog 8, e1002752.
19. She, J., Han, Z., Kim, T. W., Wang, J., Cheng, W., Chang, J., Shi, S., Wang, J., Yang, M., Wang, Z. Y., and Chai, J. (2011). Structural insight into brassinosteroid perception by BRI1. Nature 474, 472-476.
20. Pei, Q., Christofferson, A., Zhang, H., Chai, J., and Huang, N. (2011). Computational investigation of the enzymatic mechanisms of phosphothreonine lyase. Biophys Chem 157, 16-23.
21. Maekawa, T., Cheng, W., Spiridon, L. N., Toller, A., Lukasik, E., Saijo, Y., Liu, P., Shen, Q. H., Micluta, M. A., Somssich, I. E., et al. Chai, J. (2011). Coiled-coil domain-dependent homodimerization of intracellular barley immune receptors defines a minimal functional module for triggering cell death. Cell Host Microbe 9, 187-199.
22. Cheng, W., Munkvold, K. R., Gao, H., Mathieu, J., Schwizer, S., Wang, S., Yan, Y. B., Wang, J., Martin, G. B., and Chai, J. (2011). Structural analysis of Pseudomonas syringae AvrPtoB bound to host BAK1 reveals two similar kinase-interacting domains in a type III Effector. Cell Host Microbe 10, 616-626.
23. Huang, Z., and Chai, J. (2010). Mapping the selection mechanisms by bacterial GEFs. Virulence 1, 93-96.
24. Han, Z., Niu, T., Chang, J., Lei, X., Zhao, M., Wang, Q., Cheng, W., Wang, J., Feng, Y., and Chai, J. (2010b). Crystal structure of the FTO protein reveals basis for its substrate specificity. Nature 464, 1205-1209.
25. Han, Z., Huang, N., Niu, T., and Chai, J. (2010a). A loop matters for FTO substrate selection. Protein Cell 1, 616-620.
26. Chen, D., Lei, L., Flores, R., Huang, Z., Wu, Z., Chai, J., and Zhong, G. (2010). Autoprocessing and self-activation of the secreted protease CPAF in Chlamydia-infected cells. Microb Pathog 49, 164-173.
27. Liang, P., Wang, H., Chen, H., Cui, Y., Gu, L., Chai, J., and Wang, K. (2009). Structural Insights into KChIP4a Modulation of Kv4.3 Inactivation. J Biol Chem 284, 4960-4967.
28. Huang, Z., Sutton, S. E., Wallenfang, A. J., Orchard, R. C., Wu, X., Feng, Y., Chai, J., and Alto, N. M. (2009). Structural insights into host GTPase isoform selection by a family of bacterial GEF mimics. Nat Struct Mol Biol 16, 853-860.
29. Dong, J., Xiao, F., Fan, F., Gu, L., Cang, H., Martin, G. B., and Chai, J. (2009). Crystal structure of the complex between Pseudomonas effector AvrPtoB and the tomato Pto kinase reveals both a shared and a unique interface compared with AvrPto-Pto. Plant Cell 21, 1846-1859.
30. Chen, D., Chai, J., Hart, P. J., and Zhong, G. (2009). Identifying catalytic residues in CPAF, a Chlamydia-secreted protease. Arch Biochem Biophys 485, 16-23.
31. Zong, N., Xiang, T., Zou, Y., Chai, J., and Zhou, J. M. (2008). Blocking and triggering of plant immunity by Pseudomonas syringae effector AvrPto. Plant Signal Behav 3, 583-585.
32. Zhou, J. M., and Chai, J. (2008). Plant pathogenic bacterial type III effectors subdue host responses. Curr Opin Microbiol 11, 179-185.
33. Xiang, T., Zong, N., Zou, Y., Wu, Y., Zhang, J., Xing, W., Li, Y., Tang, X., Zhu, L., Chai, J., and Zhou, J. M. (2008). Pseudomonas syringae effector AvrPto blocks innate immunity by targeting receptor kinases. Curr Biol 18, 74-80.
34. Ohlson, M. B., Huang, Z., Alto, N. M., Blanc, M. P., Dixon, J. E., Chai, J., and Miller, S. I. (2008). Structure and function of Salmonella SifA indicate that its interactions with SKIP, SseJ, and RhoA family GTPases induce endosomal tubulation. Cell Host Microbe 4, 434-446.
35. Huang, Z., Feng, Y., Chen, D., Wu, X., Huang, S., Wang, X., Xiao, X., Li, W., Huang, N., Gu, L., et al. Chai, J. (2008). Structural basis for activation and inhibition of the secreted chlamydia protease CPAF. Cell Host Microbe 4, 529-542.
36. Chen, L., Wang, H., Zhang, J., Gu, L., Huang, N., Zhou, J. M., and Chai, J. (2008). Structural basis for the catalytic mechanism of phosphothreonine lyase. Nat Struct Mol Biol 15, 101-102.
37. Zhifu Han, P. L., LichuanGu, Yin Zhang, Hong Li, She Chen, Jijie Chai (2007). Structural basis for histone demethylation by JHDM1 Frontier Science 1, 52-67.
38. Zhang, J., Shao, F., Li, Y., Cui, H., Chen, L., Li, H., Zou, Y., Long, C., Lan, L., Chai, J., et al. (2007). A Pseudomonas syringae effector inactivates MAPKs to suppress PAMP-induced immunity in plants. Cell Host Microbe 1, 175-185.
39. Xing, W., Zou, Y., Liu, Q., Liu, J., Luo, X., Huang, Q., Chen, S., Zhu, L., Bi, R., Hao, Q., et al. Chai, J.(2007). The structural basis for activation of plant immunity by bacterial effector protein AvrPto. Nature 449, 243-247.
40. Wang, H., Yan, Y., Liu, Q., Huang, Y., Shen, Y., Chen, L., Chen, Y., Yang, Q., Hao, Q., Wang, K., and Chai, J. (2007). Structural basis for modulation of Kv4 K+ channels by auxiliary KChIP subunits. Nat Neurosci 10, 32-39.
41. Han, Z., Xing, X., Hu, M., Zhang, Y., Liu, P., and Chai, J. (2007). Structural basis of EZH2 recognition by EED. Structure 15, 1306-1315.
42. Zhang, T., Sun, Y., Tian, E., Deng, H., Zhang, Y., Luo, X., Cai, Q., Wang, H., Chai, J., and Zhang, H. (2006). RNA-binding proteins SOP-2 and SOR-1 form a novel PcG-like complex in C. elegans. Development 133, 1023-1033.
43. Han, Z., Guo, L., Wang, H., Shen, Y., Deng, X. W., and Chai, J. (2006). Structural basis for the specific recognition of methylated histone H3 lysine 4 by the WD-40 protein WDR5. Mol Cell 22, 137-144.
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