Phagocytosis of apoptotic cells is an integral part of the cell death program and an important event in tissue remodeling, suppression of inflammation as well as regulation of immune response. Defects in this process contribute to inflammatory diseases and autoimmune disorders.

Using Caenorhabditis elegans as a model system, we take combinatory approaches of genetics, cell biology and biochemistry to identify new genes that control various events of cell corpse clearance including apoptotic cell recognition, internalization and degradation and the mechanisms controlling lysosome dynamics and morphology change.. These characterizations and mechanistic studies of these novel players will help us to understand how phagocytosis of apoptotic cell is regulated in worm and in higher organisms like human being

1998-1999 Visiting student, Laboratory of Genetics, Gent University/VIB, Belgium 
1994-1999 Ph.D., National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, China 
 1988-1992 B.S., Microbiology, Department of Microbiology, Shandong University, China

2014- Investigator, Institute of Biophysics, Chinese Academy of Sciences
2011 -2014 Associate Investigator, National Institute of Biological Sciences, Beijing, China
2006-2011 Assistant Investigator, National Institute of Biological Sciences, Beijing,China
1999-2006 Postdoctoral research associate, Department of MCD Biology, University of Colorado, Boulder, USA

The 10th  Chinese Young Women Scientist Award 2013
National Outstanding Young Scientist Award, 2013
HHMI International Early Career Scientist Award, 2012 

   

1.Cheng S, Wang K, Zou W, Miao R2, 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---- 2015.08.03

2. Wu, Y.W., Cheng, S.Y., Zhao, H.Y., Zou, W., Yoshina, S., Mitani, S., Zhang, H., *Wang, X.C. (2014) PI3P phosphatase activity is required for autophagosome maturation and autolysosome formation. EMBO Rep. 15(9):973-81----2014.8.14

3.Wang H, Lu Q, Cheng S, *Wang X, *Zhang H(2013). Autophagy activity contributes to programmed cell death in Caenorhabditis elegans. Autophagy. 9(12):1975-82----2013.12.1

4.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):2022-32---- 2013.12.01

5.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):1163-75.---- 2013.04.15

6.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), pp 4613-4622----2012.12.03

7.*Zou W, Wang X, Vale RD, Ou G(2012).Autophagy genes promote apoptotic cell corpse clearance，Autophagy, 8(8),pp 1267-1268----2012.08

8.Zhang Y, Wang H, Kage-N, 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), pp 1276-1284----2012.07.24

9.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), pp 351-354----2012.07.20

10.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), pp1339-1350----2012.06.15

11.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), pp27-35----2012.03.26


12.Wu YC, Wang X, Xue D，Methods for Studying Programmed Cell Death in C. elegans，Methods in Cell Biology,Xue D, ELSEVIER ACADEMIC PRESS INC, 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA, pp 297-320,USA, 2012 ----2012.01.08

13.Guo P, *Wang X(2010).Rab GTPases act in sequential steps to regulate phagolysosome formation，Small GTPases,1(3), pp 170-173----2010.12.17


14.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 Genetics. 6(12), p e1001235----2010.12.09

15.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 . Proceedings of the National Academy of Sciences of the United States of America. 107(42), pp 18016-18021----2010.10.19


16.*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. Nature Cell Biology. 12(7), pp 655-664----2010.07

17.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), pp 1042-1055----2010.06.11

18.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 Genetics. 5(10), p e1000679 ----2009.10.09

19. Li W, Zou W, Zhao D, Yan J, Zhu Z, Lu J, and 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----2009.07

20.Darland-Ransom M, Wang X, Sun CL, Mapes J, Gengyo-Ando K, Mitani S, and Xue D (2008) Role of C. elegans TAT-1 protein in maintaining plasma membrane phosphatidylserine asymmetry. Science. 320(5875), 528-31----2008.04.25

21. Lu Q, Zhang Y, Hu T, Guo P, Li W, and Wang X* (2008). C. elegans Rab GTPase 2 is required for the degradation of apoptotic cells. Development. 135, 1069-1080----2008.03

22. Wang X, Wang J, Gengyo-Ando K, Gu L, Sun CL, Yang C, Shi Y, Kobayashi T, Shi Y,Mitani S, Xie XS, and Xue D (2007). C. elegans mitochondrial factor WAH-1 promotes phosphatidylserine externalization in apoptotic cells through phospholipid cramblase SCRM-1. Nat Cell Biol. 9, 541-549 ----2007.04.01

23.Yang C, Yan N, Parish J, Wang X, Shi Y, and 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----2006.02.08

24.Wang X, Wu Y, Fadok V, Lee MC, Gengyo-Ando K, Cheng L, Ledwich D, Hsu P,Chen J, Chou B, Henson P, Mitani S, and Xue D (2003). Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12.Science 302, 1563-1566----2003.11.28

25.Wang X, Yang C, Cai J, Shi Y, and Xue D (2002). Mechanisms of AIF-apoptotic DNA degradation in Caenorhabditis elegans. Science 298, 1587-1592. (Research article)----2002.11.22

26.Wang X, Bauw G, Van Damme E, Peumans W, Chen Z, Van Montagu M, Angenon G,and Dillen W (2001). Gastrodianin-like mannose-binding proteins: a novel class of plant proteins with antifungal properties，The Plant Journal, 25(6), pp 651-661----2001.03

The main research interest of my lab focuses on the understanding of how phagocytosis is regulated during programmed cell death. Phagocytosis of apoptotic cells is an integral part of the cell death program and an important event in tissue remodeling, suppression of inflammation as well as regulation of immune response. Defects in dying cell clearance contribute to inflammatory diseases and autoimmune disorders.

Despite that tremendous efforts have been made in the past decades, relatively little is known about the molecular mechanisms controlling the clearance of apoptotic cells, largely owing to the redundancy and complexity of this process as well as the lack of a real in vivo system for the higher organisms. Several fundamental questions remain elusive, for example, what are "eat-me" signals for apoptotic cell clearance? How are these signals presented on the surface of dying cells and how are they transduced to phagocytes for engulfment?

It is well known that the genetic pathway controlling programmed cell death is highly conserved from nematode to humans. The nematode Caenorhabditis elegans provides a unique system to study how programmed cell death is regulated and executed. Forward genetic studies have identified seven cell death genes (cell death abnormal, ced) that are important for phagocytosis of apoptotic cells in C. elegans. These seven genes act in two partially redundant pathways to regulate cell corpse engulfment, with ced-1, ced-7, ced-6 functioning in one pathway and ced-2, ced-5, ced-12 and ced-10 in the other. Nevertheless, the detailed mechanisms for these genes to promote dying cell clearance are still not very clear. To better understand how apoptotic cells are properly removed during apoptosis, we will take advantage of combinatory approaches to identify new components in the cell corpse engulfment-signaling pathway and uncover the mechanisms underlying this process.

Our current research includes:

1. Employing sensitized forward genetic screens to identify new engulfment genes that may be missed in the traditional forward genetic screen due to the genetic redundancy. During my postdoctoral training with Dr. Ding Xue in the University of Colorado, we characterized psr-1, the worm homolog of phosphatidylserine receptor. Our work demonstrated that PSR-1 is likely an upstream receptor for ced-2, 5, 10,12 pathway that transduces the dying cell signals, possibly through a direct interaction with CED-5 and CED-12. However, PSR-1 appears unlikely to be the only receptor in this pathway because psr-1 deletion mutant has weaker engulfment defects than the ced-2, ced-5, ced-10 and ced-12 mutants. In order to identify genes that function redundantly with psr-1, we will perform genetic screens to look for PSR-1 enhancers.

2. Using reverse genetics to search for new components involved in dying cell clearance. The availability of genome-wide RNAi library and relatively easy access to the deletion mutants generated by several knockout consortiums in the C. elegans research community will allow us to perform genome-wide RNAi screen for new players of cell corpse engulfment or determine the functions of worm homologs of mammalian phagocytosis factors by analyzing the corresponding deletion mutants in C. elegans.

3. Mechanistic studies of the identified engulfment genes in regulating cell corpse engulfment. We will take biochemical approach to dissect the functioning mechanisms of these genes, e.g., identifying their interaction partners involved in dying cell clearance. 

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Major Invited International Conference Talks
 1. Gordon Conference on “Molecular Membrane Biology”, Proctor Academy, Andover, NH, USA July 15, 2015
2. The 7th International Sympoisum on Autophagy, Huangshan, China Mar.20, 2015
3. The 4th International Symposium on Membrane Biology, Dali, China Oct. 11, 2014
4. C. elegans Development, Cell Biology and Gene Expression Meeting in association with The 6th Asia-Pacific C. elegans Meeting, Japan July 18, 2014
5. The 86th Annual Meeting of Japanese Biochemical Society, Japan Sept 11, 2013
6. Gordon Conference “Apoptotic Cell Recognition & Clearance” University of New England, USA June 24, 2013
7. Cold Spring Harbor Asia Conference on Small GTPases at different scales: Proteins, Membranes, Cells, Suzhou, China Sept 5, 2012
8. The 1st International Symposium on Membrane Biology, Guilin, China Jul. 2009
9. The 17th International C.elegans Meeting, UCLA Jun. 2009
10. The 16th International C.elegans Meeting, UCLA Jun. 2007
11. Gordon Conference “Clearance of Dying Cells: Mechanisms and Consequences” Connecticut, USA Aug.2003

Major Invited Talks 
1.Invited talk, Ewha Woman’s University, Seoul, Korea, Nov. 11, 2014
2.Invited talk, National Symposium of Developmental Biology, Lanzhou, China,
Oct. 17, 2014
3.Invited talk, 5th IGAKUKEN International Symposium on Autophagy, Tokyo, Japan Sept. 2013
4.Invited talk, National Symposium of Cell Biology, Wuhan, China April 2013
5.Invited talk, Symposium of Cell Biology, Beijing, Dec. 2012
6.Invited lecture, Tsqing hua University, China, May 2012
7.Invited lecture, National Institute of Health, Bethesda, USA, Mar. 2012
8.Invited lecture, Rockefeller University, New York, USA, Dec. 2011
9.Invited lecture, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Jan. 2011
10.Invited talk, National Symposium of Developmental Biology, Beijing, Sept. 2010
11.Invited talk, 1st Chinese C. elegans Meeting, Beijing, Oct. 2007

Other Academic Activities 
1. C. elegans Development, Cell biology, and Gene expression topic Meeting, Wisconsin, USA Scientific organizing committee Jul. 2012
2. 4th East Asia C. elegans meeting, Tokyo, Japan Chair of Development session Jul. 2010
3. C. elegans Development & Evolution Meeting, Madison, Wisconsin Chair of Cell death session Jun. 2008
4. 1st Chinese C. elegans Meeting, Beijing Co-organizer Oct. 2007
5. 16th International C.elegans Meeting, UCLA Chair of Cell death and Neurodegeneration session Jun. 2007

已指导学生

杜红伟  博士研究生  071009-细胞生物学  

现指导学生

郝田超  博士研究生  071009-细胞生物学  

刘希璐  硕士研究生  071010-生物化学与分子生物学  

胡俊岩  博士研究生  071009-细胞生物学  

陈力榕  硕士研究生  071009-细胞生物学  

廖咨冰  硕士研究生  071010-生物化学与分子生物学  

张倩倩  博士研究生  071009-细胞生物学  

王莉  硕士研究生  071009-细胞生物学  

胡斯琪  博士研究生  071009-细胞生物学  

陆治江  博士研究生  071009-细胞生物学  

http://www.ibp.cas.cn/wangxcLab/