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Xiaochen Wang

北京生命科学研究所高级研究员
Xiaochen Wang, Ph.D.
Associate Investigator, NIBS, Beijing, China
Phone: 010-80726688
Fax: 010-80726689
E-mail: wangxiaochen@nibs.ac.cn
Group Website:http://wangxchenlab.nibs.ac.cn:8080

Education

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

Research Description:

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?

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.

Publications

  1. Chen B., Jiang Y., Zeng S., Yan J., Li X., Zhang Y., Zou W., Wang X. (2010) Endocytic sorting and recycling requires membrane phosphatidylserie asymmetry maintained by TAT-1/CHAT-1. PLos Genetics 6(12):e1001235

  2. Guo P. and Wang X. (2010) Rab GTPases act in sequential steps to regulate phagolysosome formation. Small GTPases 1: 3, 1-4 (Invited Extra view)

  3. 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. PNAS 107(42):18016-21

  4. 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):655-64 (*Co-corresponding author)

  5. 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): e1000679. doi: 10.1371/journal.pgen.1000679

  6. 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(14):2445-55

  7. Lu Q., Zhang Z., Hu T., Guo P., Li W., Wang X. (2008) C. elegans Rab GTPase 2 is required for the degradation of apoptotic cells. Development 35(6):1069-1080

Address:7 Science Park Rd., ZGC life science park, Beijing 102206 Tel:+86-10-80726688 Fax:+86-10-80726689 E-mail:info@nibs.ac.cn
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