柴继杰 博士，研究员 Jijie Chai, Ph.D., Assistant Investigator, National Institute of Biological Sciences, Beijing.
电话（Tel）：010-80726688
传真（Fax）：010-80726689
E-mail：chaijijie@nibs.ac.cn
教育经历Education
1987年 大连轻工业学院化学工程系学士
B.S. Chemical Engineering, 1983-1987,
Dalian Institute of Light Industry, China
1997年 中国协和医科大学药物分析学博士
Ph.D. Medicinal Analysis, 1994-1997,
Peking Union Medical College, China
工作经历Professional Experience
2004-present National Institute of Biological Sciences, Beijing, China（中国北京生命科学研究所工作）
1999-present postdoctoral fellow, Department of Molecular Biology, Princeton University, USA（美国普林斯顿大学分子生物学系做博士后）
1997-1999 postdoctoral fellow, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China（中国科学院生物物理研究所做博士后）
研究概述：
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的结构与功能。主要通过蛋白晶体衍射的方法及一些生物、生化方面的手段阐述这些生物大分子在结构和功能上的联系。我们并不局限于已建立的研究框架，拟与北京生命科学研究所的其他研究小组合作，在今后的工作中开展一些联合研究项目。
一个正进行的研究方向将关注专职吞噬细胞（professional phagocytes）对调亡细胞的识别途径。近十年来大量的工作已对调亡调控的机制做了详尽的研究。相对的，在细胞调亡后如何去除调亡的细胞残体的问题并没得到关注。（此问题并不是不重要）如果在此环节出现问题将造成炎症反应的异常持续和自身免疫的出现。在吞噬细胞消除调亡的细胞体的过程中，第一步反应是调亡的细胞体和处于调亡过程中的细胞表面出现如磷脂酰丝氨酸（PS）等可被各种吞噬细胞上的受体识别的发出“eat-me”信号的信号分子。近年来的研究发现这一识别过程并不仅仅是此类信号分子与吞噬细胞受体的简单结合。实际上，一类可被其他吞噬细胞的受体识别的桥联分子（bridging molecule）如Annexin I（Anx I）也参与了识别过程。除此，我们还将对“don’t-eat-me”信号的识别机制及溶血磷脂酰胆碱（LPC）等“find-me”信号的产生和调控机制进行研究。前者存于正常细胞，保证这些非调亡的细胞不被错误吞噬；后者为调亡细胞所产生。
是本实验室的另一个研究目标是吞噬细胞识别和吞噬调亡细胞的信号调控的分子机制。前人在线虫（C. elegans）的遗传学筛选工作中发现七个基因产物分别隶属于两条功能上冗余的信号转导系统参与了清除调亡细胞体过程。其中一条信号系统为CED-2/ced-5/CED-12/CED10，这条信号系统保守的存于哺乳类中，其同源信号系统为CrkII/Dock180/ELMO/RAC，我门将从蛋白三维结构的尺度研究这条信号系统的活化和调控机制。
Research Description：
The main interest of the laboratory is focused on structural and functional studies of biologically and medically important macromolecules, mainly through protein crystallography, in couple with biochemical, biological and other approaches, to gain insights into structure-function relationship of these macromolecules. Our research program will embrace, but not be limited to, collaborations with the groups within National Institute of Biological Sciences, where joint projects will be initiated in the near future.
Specifically, one line of the research will be focused on the elucidation the molecular mechanisms underling the recognition of apoptotic cells by professional phagocytes. Extensive efforts have been made toward understanding the mechanisms that govern apoptosis, or programmed cell death during the last decade. In contrast, little attention has been paid to the subsequent removal of the apoptotic cells, defects of which have been implicated in the onset of persistent inflammatory disorders and autoimmunity. As the first step for apoptotic cells to be removed by phagocytes, the “eat-me” signal, like phosphatidylserine (PS) will be presented to the surface of apoptotic cells during apoptosis for recognition by different phagocyte receptors. To make things more complicated, the recognition of “eat-me” signal by receptors may not be through direct binding as shown by more recent studies. Instead, a bridging molecule, such as Annexin I (AnxI), may be required for this recognition process, which seems to be applicable to some other phagocyte receptors. We are also going to do mechanistic studies of don’t-eat-me signal that keep the nonapoptotic cells from being eaten alive and of production and regulation of the find-me signal (lysophosphatidylcholine, LPC) generated by the apoptotic cells.
Down this line, the other research program will be oriented toward understanding of the signaling pathways engaged the engulfment of apoptotic cells by phagocytes. Genetic screen of worm C. elegans has led to the identification of seven genes that constitute two partially redundant signaling cassettes are involved in the efficient elimination of apoptotic cells. One of the two signaling cassettes, CED-2/ced-5/CED-12/CED10, is highly conserved in the mammalian system, with their respective mammalian homologues being CrkII/Dock180/ELMO/RAC. We are going to work toward the structural understanding of how this conserved pathway is activated and regulated.
发表文章 Publications:
1. 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.
2. 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
3. Chai J, Shiozaki E, Srinivasula SM, Wu Q, Datta P, Alnemri ES, Shi Y, Dataa P. “Structural basis of caspase-7 inhibition by XIAP,” Cell 2001 Mar 9;104(5):769-80
4. 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 )
5. 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
