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百千万人才工程入选者

王晓晨  博士 研究员 博士生导师  

国家“杰出青年基金”、“国家百千万人才工程”获得者
中科院生物物理所,生物大分子国家重点实验室,研究组长

研究方向:(1)凋亡细胞清除的分子机制;(2)溶酶体功能调控、动态变化及稳态维持的调控机制

电子邮件:wangxiaochen@ibp.ac.cn

电       话:010-64888878

通讯地址:北京市朝阳区大屯路15号(100101)

英文版个人网页:http://english.ibp.cas.cn/en_sourcedb_ibp/rck/EN_xsszmW/202005/t20200519_341376.html

课题组网站:/wangxcLab/

简       历:

  1988 - 1992   山东大学微生物学系微生物学士

  1994 - 1999   北京大学生命科学学院植物基因工程和蛋白质工程国家重点实验室博士

  1998 - 1999   比利时根特大学/佛兰德斯生物科技研究所访问学生

  1999 - 2006   美国科罗拉多大学分子与细胞发育生物学系博士后

  2006 - 2011   北京生命科学研究所研究员

  2011 - 2015   北京生命科学研究所高级研究员

  2015 - 至今   中国科学院最新beat365下载

获奖及荣誉:

  1. 入选“2018年国务院政府特殊津贴”人员,2018

  2. 入选中国国家高层次人才特殊支持计划,2016

  3. 入选为“创新人才推进计划中青年科技创新领军人才”(中华人民共和国科学技术部),2015

  4. 入选国家百千万人才工程,授予“有突出贡献中青年专家”荣誉称号(中华人民共和国人力资源和社会保障部),2014

  5. 第十届中国青年女科学家,2013

  6. 国家杰出青年科学基金获得者,2013

  7. 霍华德·休斯医学研究所(HHMI)国际青年科学家奖,2012

  8. 药明康德生命化学研究奖学者奖,2012

社会任职:

研究方向:

  1. 凋亡细胞的吞噬及降解过程是整个细胞凋亡程序中不可缺少的一环,它在组织重塑、炎症抑制和免疫应答调控中起着重要的作用。凋亡细胞清除障碍引起诸如哮喘、类风湿性关节炎和狼疮等炎症疾病和自身免疫紊乱。

  利用秀丽隐杆线虫作为模式动物,我们综合运用遗传学、细胞生物学和生物化学等方法系统研究凋亡细胞清除的分子机制,包括凋亡信号的识别、凋亡细胞的吞噬和降解等过程。我们发现分泌型桥联分子TTR-52和NRF-5介导凋亡细胞的识别(Wang et al., Nat Cell Biol 2010; Zhang et al., Curr Biol 2012; Kang et al., Genes & Dev 2012);肌管素磷酸酶MTM-1与磷脂酰肌醇-3激酶PIKI-1和VPS-34协同调控凋亡细胞吞噬的起始和完成(Zou et al., PLoS Genet 2009; Cheng et al., JCB 2015);我们发现了多个调控凋亡细胞降解的新基因,它们在吞噬体成熟的不同阶段发挥作用(Lu et al., Development 2008; Li et al., Development 2009; Guo et al., PNAS 2010;Yin et al., JCB 2017);发现泛素化修饰对维持磷脂酰肌醇激酶VPS-34的正常功能和吞噬小体成熟的重要作用(Liu et al., JCB 2017);证明了细胞自噬通路通过VPS-34参与凋亡细胞的清除(Cheng et al., Autophagy 2013)。另外,我们还发现相同的清除机制被机体应用于非凋亡细胞的清除,如精子发生过程中产生的残余体的清除(Huang et al., Development 2012)。由于细胞凋亡及凋亡细胞清除的调控机制在进化上高度保守,我们的上述发现不仅深化了对于线虫凋亡细胞清除机制的认知,也为解析哺乳动物中相似过程的调控机制提供了重要线索。目前我们的研究专注于两个方面:1)凋亡信号磷脂酰丝氨酸选择性呈递的机制;2)进一步解析凋亡细胞降解的调控机理。

  2. 溶酶体是细胞内负责物质降解和循环的细胞器,在机体发育、代谢平衡及细胞稳态维持中发挥关键作用。溶酶体功能缺陷可引发溶酶体贮积症及神经退行性疾病。

  我们在线虫中建立了溶酶体体内观察和分析体系,发现在特定的发育阶段及胁迫条件下,溶酶体发生不同的形态及动态变化,并可能发挥的特异的生理功能。利用线虫强大的遗传筛选及分析系统,结合细胞生物学及生物化学等手段,我们将首先获得调控溶酶体动态变化的基因,解析它们的作用机制,进而揭示溶酶体功能、动态变化及稳态维持的调控机制及生理功能。目前我们已发现了两个溶酶体的关键调控因子:LAAT-1(哺乳动物同源蛋白PQLC2)作为溶酶体膜上的赖氨酸和精氨酸的转运蛋白,参与调控细胞内氨基酸的动态平衡进而影响胚胎的正常生长发育(Liu et al., Science 2012);SCAV-3(哺乳动物溶酶体膜蛋白LIMP2的同源蛋白)在维持溶酶体的完整性和动态变化中起着关键作用,其功能缺陷导致溶酶体底物降解缺陷和成虫寿命显著变短,表明溶酶体的完整性对于维持线虫的正常生理功能乃至寿命都具有重要的功能(Li et al., JCB 2016)。由于溶酶体组成及调控在进化中高度保守,我们将进一步研究线虫溶酶体调控基因在哺乳动物中同源基因的作用机制,为溶酶体相关疾病的致病机制解析、诊断和治疗提供理论依据。

承担项目情况:

代表论著:

1. Zhang Q, Li Y, Jian Y, Li M, Wang X*(2023). Lysosomal chloride transporter CLH-6 protects lysosome membrane integrity via cathepsin activation. J Cell Biol. 222(6):e202210063.

2. Leiling Shi, Youli Jian, Meijiao Li, Tianchao Hao, Chonglin Yang, Xiaochen Wang*(2022). Filamin FLN-2 promotes MVB biogenesis by mediating vesicle docking on the actin cytoskeleton. J Cell Biol, 221(7): e202201020

3. Yuan Li#, Xin Wang#, Meijiao Li, Chongli Yang, Xiaochen Wang*(2021). M05B5.4 (Lysosomal phospholipase A2) promotes disintegration of autophagic vesicles to maintain C. elegans development, Autophagy, 18(3):595-607

4. Yang, C*, and. Wang X* (2021). Lysosome biogenesis: Regulation and functions. J Cell Biol. 220(6):e202102001

5. Li X#, Sun Y#, Wang X* (2021). Probing lysosomal activity in vivo. Biophs Rep. 7(1):1-7

6. Sun Y, Li M, Zhao D, Li X, Yang C, Wang X* (2020). Lysosome activity is modulated by multiple longevity pathways and is important for lifespan extension in C.elegans. eLife. 9:e55745

7. Miao R, Li M, Zhang Q, Yang C, Wang X* (2020). An ECM-to-Nucleus Signaling Pathway Activates Lysosomes for C. elegans Larval. Dev Cell. 52:21-37

8. Gan Q, Wang X, Zhang Q, Yin Q, Jian Y, Liu Y, Xuan N, Li J, Zhou J, Liu K, Jing Y, Wang X, Yang C* (2019). The amino acid transporter SLC-36.1 cooperates with PtdIns3P 5-kinase to control phagocytic lysosome reformation.  J Cell Biol. 218 (8): 2619-2637

9. Wang Z, Zhao H, Yuan C, Zhao D, Sun Y, Wang X, Zhang H* (2019). The RBG-1-RBG-2 complex modulates autophagy activity by regulating lysosomal biogenesis and function in C. elegans. J Cell Sci, 132: jcs234195

10. Hu J,Cheng S, Wang H, Li X, Liu S, Wu M, Liu Y, Wang X* (2019). Distinct roles of two myosins in C. elegans spermatid differentiation.  PLOS Biol. 17(4): e3000211.

11. Zhang J, Liu J, Norris A, Grant BD, Wang X* (2018). A novel requirement for ubiquitin-conjugating enzyme UBC-13 in retrograde recycling of MIG-14/Wntless and Wnt signaling. Mol Biol Cell. 29(17):2098-2112

12. Liu Y, Zou W, Yang P, Wang L, Ma Y, Zhang H, Wang X* (2018). Autophagy-dependent ribosomal RNA degradation is essential for maintaining nucleotidehomeostasis during C. elegans development. eLlife. 7: e36588.

13. Liu J, Li M, Li L, Chen S, Wang X* (2018). Ubiquitination of the PI3-kinaseVPS-34 promotes VPS-34 stability and phagosome maturation. J Cell Biol. 217(1):347-360.

14. Yang C*, Wang X* (2017). Cell biology in China: Focusing on the lysosome. Traffic. 18(6):348-357.

15. Yin J#, Huang Y#, Guo P, Hu S, Yoshina S, Xuan N, Gan Q, Mitani S, Yang C, Wang X* (2017). GOP-1 promotes apoptotic cell degradation by activating the small GTPase Rab2 in C. elegans. J Cell Biol. 216(6):1775-1794.

16. Cheng S, Liu K, Yang C*, Wang X* (2017). Dissecting phagocytic removal of apoptotic cells in Caenorhabditis elegans. Methods Mol Biol. 1519:265-284.

17. Li Y, Chen B, Zou W, Wang X, Wu Y, Zhao D, Sun Y, Liu Y, Chen L, Miao L, Yang C, Wang X* (2016). The lysosomal membrane protein SCAV-3 maintains lysosome integrity and adult longevity. J Cell Biol. 215 (2):167-185.

18. Su Y, Li L, Wang H, Wang X, Zhang Z* (2016). All-in-One azides: empowered click reaction for in vivo labeling and imaging of biomolecules. Chem Commun. 52:2185-2188.

19. Wang X*, Yang C* (2016). Programmed cell death and clearance of cell corpses in Caenorhabditis elegans. Cell Mol. Life Sci. 73:2221-2236 (review article).

20. Cheng S, Wang K, Zou W, Miao R, Huang Y, Wang H, Wang X* (2015). PtdIns(4,5)P2 and PtdIns3P coordinate to regulate phagosomal sealing for apoptotic cell clearance. J Cell Biol. 210(3):485-502.

21. Zhang H, Chang JT, Guo B, Hansen M, Jia K, Kovács AL, Kumsta C, Lapierre LR, Legouis R, Lin L, Lu Q, Meléndez A, O'Rourke EJ, Sato K, Sato M,, Wang X, and Wu F* (2015). Guidelines for monitoring autophagy in Caenorhabditis elegans. Autophagy. 11(1):9-27.

22. Wu Y., Cheng S, Zhao H, Zou W, Yoshina S., Mitani S., Zhang H, Wang X* (2014). PI3P phosphatase activity is required for autophagosome maturation and autolysosome formation. EMBO Rep. 15(9):973-981.

23. Guo B, Huang J, Wu W, Feng D, Wang X, Chen Y, Zhang H* (2014). The nascent polypeptide-associated complex is essential for autophagic flux. Autophagy. 10(10):1738-1748.

24. Xu M, Liu Y, Zhao L, Gan Q, Wang X, Yang C* (2014). The lysosomal cathepsin protease CPL-1 plays a leading role in phagosomal degradation of apoptotic cells in Caenorhabditis elegans. Mol Biol Cell. 25(13):2071-2083.

25. Wang H, Lu Q, Cheng S, Wang X*, Zhang H* (2013). Autophagy activity contributes to programmed cell death in Caenorhabditis elegans. Autophagy. 9(12):1975-1982.

26. Cheng S , Wu Y , Lu Q , Yan J, Zhang H, Wang X* (2013). Autophagy genes coordinate with the class II PI3 kinase PIKI-1 to regulate apoptotic cell clearance in C. elegans. Autophagy. 9(12):2022-2032.

27. Zhang H, Wu F, Wang X, Du H, Wang X, Zhang H* (2013). The two C. elegans Atg16 homologs have partially redundant functions in the basal autophagy pathway. Autophagy. 9(12): 1965-1974.

28. Li X, Chen B, Yoshina S, Cai T, Yang F, Mitani S, Wang X* (2013). Inactivation of C. elegans aminopeptidase DNPP-1 restores endocytic sorting and recycling in tat-1 mutants. Mol Biol Cell. 24(8):1163-1175.

29. Huang J#, Wang H#, Chen Y, Wang X*, Zhang H* (2012). Residual body removal during spermatogenesis in C. elegans requires genes that mediate cell corpse clearance. Development. 139(24):4613-4622.

30. Zou W, Wang X, Vale RD, Ou G* (2012). Autophagy genes promote apoptotic cell corpse clearance. Autophagy. 8(8):1267-1268.

31. Zhang Y, Wang H, Kage-Nakadai E, Mitani S, Wang X* (2012). C. elegans secreted lipid-binding protein NRF-5 mediates PS appearance on phagocytes for cell corpse engulfment. Current Biol. 22(14):1276-1284.

32. Liu B#, Du H#, Rutkowski R, Gartner A, Wang X* (2012). LAAT-1 is the lysosomal lysine/arginine transporter that maintains amino acid homeostasis. Science. 337(6092):351-354.

33. Kang Y#, Zhao D#, Liang H#, Liu B, Zhang Y, Liu Q, Wang X*, Liu Y* (2012). Structural study of TTR-52 reveals the mechanism by which a bridging molecule mediates apoptotic cell engulfment. Genes & Dev. 26(12):1339-1350.

34. Li W, Zou W, Yang Y, Chai Y, Chen B, Cheng S, Tian D, Wang X*, Vale RD*, Ou G* (2012). Autophagy genes function sequentially to promote apoptotic cell corpse degradation in the engulfing cell. J Cell Biol. 197(1):27-35.

35. Wu YC, Wang X, Xue D (2012). Methods for Studying Programmed Cell Death in C. elegans. Methods i Cell Biol. Elsevier Academic Press, pp 297-320.

36. Chen B, Jiang Y, Zeng S, Yan J, Li X, Zhang Y, Zou W, Wang X* (2010). Endocytic sorting and recycling require membrane phosphatidylserine asymmetry maintained by TAT-1/CHAT-1. PLoS Genet. 6(12):e1001235.

37. Guo P, Wang X* (2010). Rab GTPases act in sequential steps to regulate phagolysosome formation. Small GTPases. 1(3):170-173.

38. Guo P, Hu T, Zhang J, Jiang S, Wang X* (2010). Sequential action of Caenorhabditis elegans Rab GTPases regulates phagolysosome formation during apoptotic cell degradation. Proc Natl Acad Sci U S A. 107(42):18016-18021.

39. Wang X*, Li W, Zhao D, Liu B, Shi Y, Chen, B, Yang H, Guo P, Geng X, Shang Z, Peden E, Kage-Nakadai E, Mitani S, Xue D * (2010). Caenorhabditis elegans transthyretin-like protein TTR-52 mediates recognition of apoptotic cells by the CED-1 phagocyte receptor. Nat Cell Biol. 12(7):655-664.

40. Tian Y, Li Z, Hu W, Ren H, Tian E, Zhao Y, Lu Q, Huang X, Yang P, Li X, Wang X, Kovacs AL, Yu L*, Zhang H* (2010). C. elegans screen identifies autophagy genes specific to multicellular organisms. Cell. 141(6):1042-1055.

41. Zou W, Lu Q, Zhao D, Li W, Mapes J, Xie Y, Wang X* (2009). Caenorhabditis elegans myotubularin MTM-1 negatively regulates the engulfment of apoptotic cells. PLoS Genet. 5(10):e1000679.

42. Li W, Zou W, Zhao D, Yan J, Zhu Z, Lu J, Wang X* (2009). C. elegans Rab GTPase activating protein TBC-2 promotes cell corpse degradation by regulating the small GTPase RAB-5. Development. 136:2445-2455.

43. Lu Q#, Zhang Y#, Hu T, Guo P, Li W, Wang X* (2008). C. elegans Rab GTPase 2 is required for the degradation of apoptotic cells. Development. 135:1069-1080.

44. Darland-Ransom M, Wang X, Sun CL, Mapes J, Gengyo-Ando K, Mitani S, Xue D* (2008). Role of C. elegans TAT-1 protein in maintaining plasma membrane phosphatidylserine asymmetry. Science. 320(5875):528-531.

45. Wang X, Wang J, Gengyo-Ando K, Gu L, Sun CL, Yang C, Shi Y, Kobayashi T, Shi Y,Mitani S, Xie XS, Xue D* (2007). C. elegans mitochondrial factor WAH-1 promotes phosphatidylserine externalization in apoptotic cells through phospholipid scramblase SCRM-1. Nat Cell Biol. 9:541-549.

46. Yang C, Yan N, Parish J, Wang X, Shi Y, Xue D* (2006). RNA aptamers targeting the cell death inhibitor CED-9 induce cell killing in Caenorhabditis elegans. J Biol Chem. 281(14): 9137-9144.

47. Wang X#, Wu Y#, Fadok VA, Lee MC, Gengyo-Ando K, Cheng LC, Ledwich D, Hsu PK, Chen JK, Chou BK, Henson P, Mitani S, Xue D* (2003). Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12. Science. 302:1563-1566.

48. Wang X#, Yang C#, Cai J, Shi Y, Xue D* (2002). Mechanisms of AIF-apoptotic DNA degradation in Caenorhabditis elegans. Science. 298:1587-1592 (Research article).

49. Wang X, Bauw G, Van Damme EJ, Peumans WJ, Chen ZL, Van Montagu M, Angenon G, Dillen W* (2001). Gastrodianin-like mannose-binding proteins: a novel class of plant proteins with antifungal properties,Plant J. 25(6):651-661.

(资料来源:王晓晨研究员,2023-08-03)