Education

1988 - 1992 B.S., Microbiology, Department of Microbiology, Shandong University, China

1994 - 1999 Ph.D., National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, China

1998 - 1999 Visiting student, Laboratory of Genetics, Gent University/VIB, Belgium

1999 - 2005 Postdoctoral research associate, Department of MCD Biology, University of Colorado, Boulder, USA

Professional Experience

1998 - 1999 Visiting student, Laboratory of Genetics, Gent University/VIB, Belgium

1999 - 2006 Postdoctoral research associate, Department of MCD Biology, University of Colorado, Boulder, USA

2006 - 2011 Assistant Investigator, National Institute of Biological Sciences, Beijing, China

2011 - 2014 Associate Investigator, National Institute of Biological Sciences, Beijing, China

2015 - Principal Investigator Institute of Biophysics, Chinese Academy of Science

2012 HHMI International Early Career Scientist Award

2013 The 10^thChinese Young Women Scientist Award

2013 National Outstanding Young Scientist Award

Our laboratory investigates how apoptotic cells are properly removed during programmed cell death and how lysosome dynamics and functions are regulated usingC. elegansas a model system. Employing combinatory approaches of genetics, cell biology and biochemistry, we have been systemically identifying new genes and dissecting regulatory mechanisms controlling various aspects of apoptotic cell removal including recognition, internalization and degradation of cell corpses. We have identified secretory bridging molecules TTR-52 and NRF-5 that mediate recognition of cell corpses by phagocytes (Wang et al.,Nat Cell Biol2010; Zhang et al.,Curr Biol2012; Kang et al.,Genes & Dev2012). We found that myotubularin phosphatase MTM-1 coordinates with the PI3 kinases PIKI-1 and VPS-34 to control initiation and completion of cell corpse engulfment (Zou et al.,PLoS Genet2009; Cheng et al.,JCB2015). We identified regulators of phagosome maturation, which act at sequential steps to promote cell corpse degradation (Lu et al.,Development2008; Li et al.,Development2009; Guo et al.,PNAS2010). Moreover, we found that non-apoptotic targets like residual bodies generated during spermatogenesis are recognized and cleared by the same molecular machinery that removes apoptotic cells (Huang et al.,Development2012). In addition, we demonstrate that the autophagy pathway contributes to cell corpse clearance through the PI3 kinase VPS-34 (Cheng et al.,Autophagy2013). As evolutionarily conserved mechanisms are utilized to remove apoptotic cells, these findings have greatly advanced our understanding of apoptotic cell clearance in both worms and mammals. Our current research focuses on the investigation of selective exposure of the PtdSer “eat me” signal and the further dissection of the regulatory machinery controlling cell corpse degradation.

More recently, we discovered that lysosomes undergo a variety of dynamic changes inC. elegans, which appears to associate with specific developmental stages and stress conditions. By developing and employingC. elegansas a multicellular genetic model for a systemic investigation of lysosome dynamics and function, we aim to identify signals/cellular processes that trigger/involve such lysosomal changes, dissect underlying regulatory mechanisms and reveal the physiological significance. Up to date, two key regulators of lysosomes have been identified, (1) We demonstrate that LAAT-1 (and its human counterpart, PQLC2) exports lysine and arginine from lysosomal lumen and thus maintains amino acid homeostasis for normal embryogenesis (Liu et al.,Science2012); (2) We identified SCAV-3, theC. eleganshomologue of human LIMP2, as a key regulator of lysosome integrity and dynamics, and found that maintenance/modulation of lysosome integrity by SCAV-3 and the insulin/IGF-1 signaling pathway affects longevity (Li et al.,JCB2016). We have now developed research tools to monitor and analyze lysosome dynamics and functions in liveC. elegans. We are taking combinatory approaches of genetics and cell biology to identify genes and characterize their functions in this process.

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 maintainC. elegansdevelopment,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 inC.elegans.eLife. 9:e55745

7. Miao R, Li M, Zhang Q, Yang C,Wang X*(2020). An ECM-to-Nucleus Signaling Pathway Activates Lysosomes forC. elegansLarval.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 inC. 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 inC. elegansspermatid 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 duringC. elegansdevelopment.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 inC. elegans.J Cell Biol. 216(6):1775-1794.

16. Cheng S, Liu K, Yang C*,Wang X*(2017). Dissecting phagocytic removal of apoptotic cells inCaenorhabditis 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 inCaenorhabditis 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 inCaenorhabditis 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 inCaenorhabditis 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 inCaenorhabditis 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 inC. elegans.Autophagy.9(12):2022-2032.

27. Zhang H, Wu F, Wang X, Du H,Wang X, Zhang H* (2013). The twoC. elegansAtg16 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 ofC. elegansaminopeptidase 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 inC. elegansrequires 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. eleganssecreted 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 inC. 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 ofCaenorhabditis elegansRab 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 eleganstransthyretin-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. elegansscreen 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 elegansmyotubularin 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. elegansRab 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. elegansRab 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 ofC. elegansTAT-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. elegansmitochondrial 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 inCaenorhabditis 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 byC. elegansphosphatidylserine 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 inCaenorhabditis 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.

(From Xiaochen Wang, August 3, 2023)