柴繼傑

1987.09－1991.09擔任丹東鴨綠江造紙廠助理工程師。

1997.09－1999.08中科院生物物理研究所博士后。

1999.09－2004.07普林斯頓大學博士后。

2004.07－2009.03擔任北京生命科學研究所研究員。

2009.03－至今擔任清華大學生命科學學院教授。

主要研究在生物學及藥學應用中的重要大分子的結構與功能。

一個正進行的研究方向將關注專職吞噬細胞（professional phagocytes）對調亡細胞的識別途徑。近十年大量的工作已對調亡調控的機製做了詳盡的研究。相對的，在細胞調亡后如何去除調亡的細胞殘體的問題並沒得到關注。（此問題並不是不重要）如果在此環節出現問題將造成炎症反應的異常持續和自身免疫的出現。在吞噬細胞消除調亡的細胞體的過程中，第一步反應是調亡的細胞體和處於調亡過程中的細胞表面出現如磷脂醯絲氨酸（PS）等可被各種吞噬細胞上的受體識別的發出“eat-me”信號的信號分子。研究發現這一識別過程並不僅僅是此類信號分子與吞噬細胞受體的簡單結合。實際上，一類可被其他吞噬細胞的受體識別的橋聯分子（bridging molecule）如Annexin I（Anx I）也參與了識別過程。除此，我們還將對“don’t-eat-me”信號的識別機制及溶血磷脂醯膽鹼（LPC）等。

"find-me"信號的產生和調控機制進行研究。前者存於正常細胞，保證這些非調亡的細胞不被錯誤吞噬；後者為調亡細胞所產生，是本實驗室的另一個研究目標是吞噬細胞識別和吞噬調亡細胞的信號調控的分子機制。前人在線蟲（C. elegans）的遺傳學篩選工作中發現七個基因產物分別隸屬於兩條功能上冗餘的信號轉導系統參與了清除調亡細胞體過程。其中一條信號系統為CED-2/ced-5/CED-12/CED10，這條信號系統保守的存於哺乳類中，其同源信號系統為CrkII/Dock180/ELMO/RAC，我門將從蛋白三維結構的尺度研究這條信號系統的活化和調控機制。

論文

Zhiwei Huang, Sarah E. Sutton, Adam J. Wallenfang, Robert C. Orchard, Xiaojing Wu, Yingcai Feng, Jijie Chai*, and Neal M. Alto*. Structural insights into GEF mimicry and host GTPase isoform selection by two bacterial type III effector families (*Co-corresponding authors). Nat. Struct. Mol & Biol., 2009 (in press). Jing Dong, Fangming Xiao, Fenxia Fan, Lichuan Gu, Huaixing Cang, Gregory B. Martin* and Jijie Chai*. Crystal structure of the complex between Pseudomonas effector AvrPtoB and the Pto tomato kinase reveals it has both a shared and a unique interface compared with AvrPto-Pto (*Co-corresponding authors), Plant Cell, 2009 (in press).

Structural basis for activation and inhibition of the secreted chlamydia protease CPAF. Cell Host & Microbe. 2008，4(6), 529-546. Zhiwei Huang, Yingcai Feng, Ding Chen, Xiaojing Wu, Siyang Huang, Xiaojun Wang, Xingguo Xiao, Wenhui Li, Niu Huang, Lichuan Gu, Guangming Zhong and Jijie Chai.

Maikke B. Ohlson, Zhiwei Huang, Neal M. Alto, Marie-Pierre Blanc, Jack E. Dixon, Chai J.*, and Samuel I. Miller*. Structure and function of SifA indicate that interactions with SKIP, SseJ, and RhoA family GTPases induce endosomal tabulation (*Co-corresponding authors). Cell Host & Microbe. 2008, 4(5):434-46.

Zhou JM, Chai J. Plant pathogenic bacterial type III effectors subdue host responses. Curr Opin Microbiol. 2008 Apr; 11(2):179-85.

Xiang T, Zong N, Zou Y, Wu Y, Zhang J, Xing W, Li Y, Tang X, Zhu L, Chai J, Zhou JM. Pseudomonas syringae Effector AvrPto Blocks Innate Immunity by Targeting Receptor Kinases. Curr Biol. 2008 Jan 8; 18(1):74-80.

Chen L, Wang H, Zhang J, Gu L, Huang N, Zhou JM, Chai J. Structural basis for the catalytic mechanism of phosphothreonine lyase. Nat Struct Mol Biol. Nat Struct Mol Biol. 2008 Jan; 15(1):101-2.

Han Z, Xing X, Hu M, Zhang Y, Liu P, Chai J.Structural basis of EZH2 recognition by EED. Structure. 2007 Oct; 15(10):1306-15.

Xing W, Zou Y, Liu Q, Liu J, Luo X, Huang Q, Chen S, Zhu L, Bi R, Hao Q, Wu JW, Zhou JM, Chai J. The structural basis for activation of plant immunity by bacterial effector protein AvrPto. Nature. 2007 Sep 13; 449(7159):243-7.

Zhang J, Shao F, Li Y, Cui H, Chen L, Li H, Zou Y, Long C, Lan L, Chai J, Chen S, Tang X, Zhou JM. Cell Host & Microbe. 2007 May 17, 1(3):175-85.

Wang H, Yan Y, Liu L, Huang H, Shen Y, Chen L, Chen Y, Yang Q, Hao Q, Wang K, Chai J, Structural Basis for Modulation of Kv4 K+ Channels by Auxiliary KChIP Subunits. Nature Neuroscience, 2007 Jan; 10(1):32-9.

Zhang T, Sun Y, Tian E, Deng H, Zhang Y, Luo X, Cai Q, Wang H, Chai J, Zhang H. RNA-binding proteins SOP-2 and SOR-1 form a novel PcG-like complex in C. elegans. Development. 2006 Mar; 133(6):1023-33.

Han Z, Guo L, Wang H, Shen Y, Deng XW, Chai J. Structural basis for the specific recognition of methylated histone H3 lysine 4 by the WD-40 protein WDR5. Mol. Cell 2006, 22(1):137-44.

Yan N, Wu JW, Chai J, Li W, Shi Y. Molecular mechanisms of DrICE inhibition by DIAP1 and removal of inhibition by Reaper, Hid and Grim. “Nat Struct Mol Biol. 2004 May;11(5):420-8. Epub 2004 Apr 25.”

Yan N, Chai J, Lee ES, Gu L, Liu Q, He J, Wu J-W, Kokel D, Li H, Hao Q, Xue .D, and Shi Y. Structure of the CED-4/CED-9 complex reveals insights into programmed cell death in Caenorhabditis elegans. Nature, 2005 Oct 6; 437(7060):831-7.

Chai J*, Yan N*, Huh JR, Wu JW, Li W, Hay BA, Shi Y. “Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination.” Nat Struct Biol. 2003 Nov; 10(11):892-8. (* These authors contributed equally to the work ).

Yan N, Gu L, Kokel D, Chai J, Li W, Han A, Chen L, Xue D, Shi Y. Structural, biochemical, and functional analyses of CED-9 recognition by the proapoptotic proteins EGL-1 and CED-4. Mol Cell. 2004 15(6):999-1006.

Yan N, Wu JW, Chai J, Li W, Shi Y. Molecular mechanisms of DrICE inhibition by DIAP1 and removal of inhibition by Reaper, Hid and Grim. Nat Struct Mol Biol. 2004, 11(5):420-8.

Chai J, Wu JW, Yan N, Massagué J, Pavletich NP, Shi Y. Features of a Smad3 MH1-DNA complex. Roles of water and zinc in DNA binding. J Biol Chem. 2003, 278(22):20327-3.

Shiozaki EN, Chai J, Rigotti DJ, Riedl SJ, Li P, Srinivasula SM, Alnemri ES, Fairman R, Shi Y. Mechanism of XIAP-mediated inhibition of caspase-9. Mol Cell. 2003, 11(2):519.

Wang X, Yang C, Chai J, Shi Y, Xue D. Mechanisms of AIF-mediated apoptotic DNA degradation in Caenorhabditis elegans. Science. 2002 Nov 22; 298(5598):1587-92.

Wu JW, Krawitz AR, Chai J, Li W, Zhang F, Luo K, Shi Y. Structural mechanism of Smad4 recognition by the nuclear oncoprotein Ski: insights on Ski-mediated repression of TGF-beta signaling. Cell. 2002, 111(3):357-67.

Li W, Srinivasula SM, Chai J, Li P, Wu JW, Zhang Z, Alnemri ES, Shi Y. Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi. Nat Struct Biol. 2002, 9(6):436.

Shiozaki EN, Chai J, Shi Y. Oligomerization and activation of caspase-9, induced by Apaf-1 CARD. Proc Natl Acad Sci U S A. 2002, 99(7):4197-202.

Wu JW, Hu M, Chai J, Seoane J, Huse M, Li C, Rigotti DJ, Kyin S, Muir TW, Fairman R, Massagué J, Shi Y. Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling. Mol Cell. 2001, 8(6):1277

Chai J, Wu Q, Shiozaki E, Srinivasula SM, Alnemri ES, Shi Y. “Crystal structure of a procaspase-7 zymogen: mechanisms of activation and substrate binding,” Cell 2001 Nov 2;107(3):399-407.

Wu JW, Cocina AE, Chai J, Hay BA, Shi Y. Structural analysis of a functional DIAP1 fragment bound to grim and hid peptides. Mol Cell. 2001, 8(1):95

Srinivasula SM, Hegde R, Saleh A, Datta P, Shiozaki E, Chai J, Lee RA, Robbins PD, Fernandes-Alnemri T, Shi Y, Alnemri ES. A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature. 2001 Mar 1; 410(6824):112-6.

Chai J, Shiozaki E, Srinivasula SM, Wu Q, Datta P, Alnemri ES, Shi Y. Structural basis of caspase-7 inhibition by XIAP. Cell. 2001 Mar 9; 104(5):769-80.

Wu G*, Chai J*, Suber TL, Wu JW, Du C, Wang X, Shi Y. “Structural basis of IAP recognition by Smac/DIABLO,” Nature 2000 Dec 21-28; 408 (*These authors contributed equally to the work ).

Chai J , Du C, Wu JW, Kyin S, Wang X, Shi Y. Structural and biochemical basis of apoptotic activation by Smac/DIABLO. Nature. 2000 Aug 24; 406(6798):855-62.

擔任中國生物物理學會、分子生物物理專業委員會理事及副主任，中國晶體學會理事，中國生物化學與分子生物學學會、蛋白質專業委員會委員，中國生物化學與分子生物學學會、蛋白質專業委員會委員。