Committee

Xiaodong Wang

E-mail :

Job title :
Member of the National Academy of Sciences, USA

Office Address : 7 Science Park Road ZGC Life Science Park, Beijing

EDUCATION EXPERIENCE

1991-1995 Postdoctoral research with Drs. Joseph L. Goldstein and Michael S. Brown, UT-Southwestern, studies on sterol regulation of gene expression.
1986-1991 Ph.D.dissertation research with Dr. Richard A. Padgett, UT-Southwestern. Studies on mammalian pre-messenger RNA splicing.
1984-1985 Undergraduate thesis with Professor Shaobai Xue, BeijingNormal University. Studies on mammalian cell cycle control.

WORK EXPERIENCE

2004 NAS Award in Molecular Biology, elected to National Academy of Sciences, USA
2003- Investigator, National Institute of Biological Sciences,Beijing, China
2002- present Investigator, Howard Hughes Medical Institute.
2001- present George L. MacGregor Distinguished Chair Professor in Biomedical Science, UT-Southwestern.
1999-2001 Associate Professor, Department of 1997-Biochemistry, Universityof Texas Southwestern Medical Center at Dallas.
1997-2002 Assistant Investigator, Howard Hughes Medical Institute.
1996-1999 Assistant Professor, Department of Biochemistry, Universityof Texas Southwestern Medical Center at Dallas.
1995-1996 Assistant Professor, Department of Biochemistry, Emory University School of Medicine, studies on the biochemical pathway of apoptosis in mammalian cells.

RESEARCH DESCRIPTION

2004 NAS Award in Molecular Biology, elected to National Academy of Sciences, USA
2003- Investigator, National Institute of Biological Sciences,Beijing, China
2002- present Investigator, Howard Hughes Medical Institute.
2001- present George L. MacGregor Distinguished Chair Professor in Biomedical Science, UT-Southwestern.
1999-2001 Associate Professor, Department of 1997-Biochemistry, Universityof Texas Southwestern Medical Center at Dallas.
1997-2002 Assistant Investigator, Howard Hughes Medical Institute.
1996-1999 Assistant Professor, Department of Biochemistry, Universityof Texas Southwestern Medical Center at Dallas.
1995-1996 Assistant Professor, Department of Biochemistry, Emory University School of Medicine, studies on the biochemical pathway of apoptosis in mammalian cells.

SELECTED PUBLICATIONS

1. Li D, Xu T, Cao Y, Wang H, Li L, Chen S, Wang X, Shen Z.(2015). A cytosolic heat shock protein 90 and cochaperone CDC37 complex is required for RIP3 activation during necroptosis. Proc Natl Acad Sci U S A 2015 Apr 7;112(16):5017-22.
2. Xian Jiang, Hui Jiang, Zhirong Shen, Xiaodong Wang.(2014). Activation of mitochondrial protease OMA1 by Bax and Bak promotes cytochrome c release during apoptosis. Proc Natl Acad Sci U S A 2014 Oct 1;111(41):14782-7.
3. Wang H, Sun L, Su L, Rizo J, Liu L, Wang LF, Wang FS, Wang X. (2014).  Mixed Lineage Kinase Domain-like Protein MLKL Causes Necrotic Membrane Disruption upon Phosphorylation by RIP3. Mol Cell.  Apr 10; 54(1):133-46.
4. Gelin Wang, Xiaoming Wang, Hong Yu, Shuguang Wei, Noelle Williams, Daniel L Holmes,Randal Halfmann, Jacinth Naidoo, Lai Wang, Lin Li, She Chen, Patrick Harran, Xiaoguang Lei & Xiaodong Wang.(2013). Small-molecule activation of the TRAIL receptorDR5 in human cancer cells  Nature Chemical Biology9,84–89.
5. Wang Z, Jiang H, Chen S, Du F, Wang X. (2012). The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell 148(1-2):228-43.
6. Sun L, Wang H, Wang Z, He S, Chen S, Liao D, Wang L, Yan J, Liu W, Lei X, Wang X. (2012). Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell 148(1-2):213-27.
7. Shang L, Chen S, Du F, Li S, Zhao L, Wang X. (2011). Nutrient starvation elicits an acute autophagic response mediated by Ulk1 dephosphorylation and its subsequent dissociation from AMPK. Proc. Natl. Acad. Sci. USA.
8. Fang M, Shen Z, Huang S, Zhao L, Chen S, Mak TW, Wang X. (2010). The ER UDPase ENTPD5 promotes protein N-glycosylation, the Warburg effect, and proliferation in the PTEN pathway. Cell 143, 711-724.
9. Petersen SL, Peyton M, Minna JD, Wang X. (2010). Overcoming cancer cell resistance to Smac mimetic induced apoptosis by modulating cIAP-2 expression. Proc. Natl. Acad. Sci. USA.  107, 11936-11941.
10. He, S., Wang, L., Miao, L., Wang, T., Du, F., Zhao, L., and Wang, X. (2009). Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 137, 1100-1111.
11. Wang, L., Du, F., and Wang, X. (2008). TNF-alpha induces two distinct caspase-8 activation pathways. Cell 133, 693-703.
12. Kim, H.E., Jiang, X., Du, F., and Wang, X. (2008). PHAPI, CAS, and Hsp70 promote apoptosome formation by preventing Apaf-1 aggregation and enhancing nucleotide exchange on Apaf-1. Mol. Cell 30, 239-247.
13. Petersen, S.L., Wang, L., Yalcin-Chin, A., Li, L., Peyton, M., Minna, J., Harran, P., and Wang, X. (2007). Autocrine TNFalpha signaling renders human cancer cells susceptible to Smac-mimetic-induced apoptosis. Cancer Cell 12, 445-456.
14. Wang, G., Shang, L., Burgett, A.W., Harran, P.G., and Wang, X. (2007). Diazonamide toxins reveal an unexpected function for ornithine delta-amino transferase in mitotic cell division. Proc. Natl. Acad. Sci. USA. 104, 2068-2073.
15. Kim, H.E., Du, F., Fang, M., and Wang, X. (2005). Formation of apoptosome is initiated by cytochrome c-induced dATP hydrolysis and subsequent nucleotide exchange on Apaf-1. Proc. Natl. Acad. Sci. USA. 102, 17545-17550.
16. Qing Zhong, Wenhua Gao, Fenghe Du, and Xiaodong Wang (2005). Mule/ARF-BP1, a BH3-Only E3 Ubiquitin Ligase, Catalyzes the Polyubiquitination of Mcl-1 and Regulates Apoptosis. Cell, 121, 1085–1095.
17. Zhenyue Hao, Gordon S. Duncan, Chia-Che Chang, Andrew Elia, Min Fang, Andrew Wakeham, itoshi Okada, Thomas Calzascia, YingJu Jang, Annick You-Ten, Wen-Chen Yeh, Pamela Ohashi, Xiaodong Wang, and Tak W. Mak (2005). Specific Ablation of the Apoptotic Functions of Cytochrome c Reveals a Differential Requirement for Cytochrome c and Apaf-1 in Apoptosis. Cell, 121, 579–591.
18. Peng Li, Deepak Nijhawan, and Xiaodong Wang (2004). Mitochondrial activation of apoptosis. Cell 116, S57-59.
19. Jiang X, Wang X. (2004). Cytochrome C-mediated apoptosis. Annu Rev Biochem. 73:87-106.
20. Lin Li, Ranny Mathew Thomas, Hidetaka Suzuki, Jef K. De Brabander, Xiaodong Wang, Patrick G. Harran, "A Small Molecule Smac Mimic Potentiates TRAIL- and TNF-Mediated Cell Death" Science, 305(5689):1471-1474, September 2004.
21. Jianhua Zhang, Mei Dong, Lily Li, Yunxia Fan, Purnima Pathre, Jin Dong, Danwen Lou, James M. Wells, Danyvid Olivares-Villagómez, Luc Van Kaer, Xiaodong Wang, and Ming Xu (2003). Endonuclease G is required for early embryogenesis and normal apoptosis in mice. Proc. Natl. Acad. Sci. USA. 100, 15782-15787.
22. Qinghua Liu, Tim A. Rand, Savitha Kalidas, Fenghe Du, Hyun-Eui Kim, Dean P. Smith and (2003). R2D2, a bridge between the initiation and effector steps of the Drosophila RNAi pathway. Science 301, 1921-1925.
23. Deepak Nijhawan, Min Fang, Elie Traer, Qing Zhong, Wenhua Gao, Fenghe Du and Xiaodong Wang (2003). Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation. Genes & Dev. 17, 1475-1486.
24. Xuejun Jiang, Hyun-Eui Kim, Hongjun Shu, Yingmin Zhao, Haichao Zhang, James Kofron, Jennifer Donnelly, Dave Burns, Shi-chung Ng, Saul Rosenberg, and Xiaodong Wang (2003). Distinctive roles of PHAP proteins and prothymosin-αin a death Regulatory Pathway. Science 299, 223-226.
25. Mohanish Deshmukh, Chunying Du, Xiaodong Wang, and Eugene M. Johnson, Jr. (2002). Exogenous Smac induces competence and permits caspase activation in sympathetic neurons. J. Neurosci. 22, 8018-8027.
26. Hitoshi Okada, Woong-Kyung Suh, Jianping Jin, Minna Woo, Chunying Du, Andrew Elia, Gordon S. Duncan, Andrew Wakeham, Annick Itie, Scott W. Lowe, Xiaodong Wang, and Tak W. Mak (2002). Generation and characterization of Smac/DIABLO-deficient mice. Mol. Cell. Biol. 22, 3509-3517.
27. Devrim Acehan, Xuejun Jiang, David Gene Morgan, John E. Heuser, Xiaodong Wang and Christopher W. Akey (2002). Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation. Mol. Cell 9. 423-432.
28. Jonathan P. Carson, Marcelina Behnam, Jennifer N. Sutton, Chunying Du, Xiaodong Wang, Donald F. Hunt, Michael J. Weber, and George Kulik. (2002). Smac Is Required for Cytochrome c-induced Apoptosis in Prostate Cancer LNCaP Cells. Cancer Res. 62. 18-23.
29. Xiaodong Wang (2001). The expanding role of mitochondria in apoptosis. Genes & Dev. 15, 2922-2933.
30. Michael Lutter, Guy Perkins, Xiaodong Wang (2001). The pro-apoptotic Bcl-2 family member tBid localizes to mitochondrial contact site. BMC Cell Biology 2, 22.
31. Piotr Widlak, Lily Y. Li, Xiaodong Wang, and William T. Garrard (2001) Action of recombinant human apoptotic endonuclease G on naked DNA and chromatin substrates: Cooperation with exonuclease and DNase I. J. Biol. Chem. 276, 48404-48409.
32. Narimon Honarpour, Sandra Gilbert, Bruce Lahn, Xiaodong Wang, and Joachim Herz (2001) Apaf-1 deficiency and neural tube closure defects are found in fog mice. Proc. Natl. Acad. Sci. USA. 98, 9683-9687.
33. Jay Parrish, Lily Li, Kristina Klotz, Duncan Ledwich, Xiaodong Wang and Ding Xue (2001) The C. elegans mitochondrial nuclease Endonuclease G is important for DNA fragmentation and progression of apoptosis. Nature 412, 90-94.
34. Lily Y. Li, Xu Luo, and Xiaodong Wang (2001) Endonuclease G (EndoG) is an apoptotic DNase when released from Mitochondria. Nature 412, 95-99.
35. Marisan Mejillano, Masaya Yamamoto, Andrew L Rozelle, Hui-Qiao Sun, Xiaodong Wang, and Helen L Yin (2001). Regulation of apoptosis by phosphatidylinositol 4, 5 Bisphosphate inhibition of caspases, and caspase inactivation of phosphatidylinositol phosphate 5 kinases. J. Biol. Chem. 276, 1865-1872.
36. Tianning Yu, Xiaodong Wang, Cherie Purring-Koch, Yen Wei, and George L. McLendon (2001). A Mutational epitope for proapoptotic cytochrome c binding to the apoptotic protease activation factor-1(Apaf-1). J. Biol. Chem. 276, 13034-13038.
37. Geng Wu, Jijie Chai, Tomeka Suber, Jia-Wei Wu, Chunying Du, Xiaodong Wang, and Yigong Shi (2000). Structural basis of IAP recognition by Smac/DIABLO. Nature 408, 1008-1012.
38. Xuejun Jiang and Xiaodong Wang (2000). Cytochrome c promotes caspase-9 activation by inducing nucleotide binding to Apaf-1. J. Biol. Chem. 275, 31199-31203.
39. Jijie Chai, Chunying Du, Jia-Wei Wu, Saw Kyin, Xiaodong Wang, and Yigong Shi (2000). Structural and biochemical basis of apoptotic activation by Smac/DIABLO. Nature 406, 855-862.
40. Michael Lutter, Min Fang, Xu Luo, Masahiro Nishijima, Xiao-song Xie, and Xiaodong Wang (2000). Cardiolipin provides specificity for Bid targeting to mitochondria. Nature Cell Biol. 2, 754-756.
41. Chunying Du, Min Fang, Yucheng Li, Lily Li, and Xiaodong Wang (2000). Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102, 33-42.
42. Dori, A. Thomas, Chunying du, Ming Xu, Xiaodong Wang, and Timothy J. Ley (2000). DFF45/ICAD can be directly processed by Granzyme B duirng the induction of apoptosis. Immunity 12, 621-632.
43. Davide Genini, Imawati Budihardjo, William Plunkett, Xiaodong Wang, Carlos J. Carrera, Howard B. Cottam, Dennis A. Carson, and Lorenzo M. Leoni. (2000). Nucleotide Requirements for the in Vitro Activation of the Apoptosis Protein-activating Factor-1-mediated Caspase Pathway. J. Biol. Chem. 275, 29-34.
44. Kang Li, Yucheng Li, John M. Shelton, James A. Richardson, Erika Spencer, Zhijian J. Chen, Xiaodong Wang, and R. Sanders Williams (2000). Cytochrome c deficiency causes embryonic lethality and attenuates stress-induced apoptosis. Cell 101, 389–399.
45. Piotr Widlak, Peng Li, Xiaodong Wang, and William T. Garrard (2000). Cleavage preferences of the apoptotic endonuclease DFF40 (caspase-activated DNase or nuclease) on naked DNA and chromatin substrates. J. Biol. Chem. 275, 8226-8232.
46. Narimon Honarpour, Chunying Du,, James A. Richardson, Robert E. Hammer, Xiaodong Wang, and Joachim Herz (2000). Adult Apaf-1 deficient mice exhibit male infertility. Dev. Biol. 218, 248-258.
47. Xuesong Liu and Xiaodong Wang (2000). In vitro assays for caspase-3 activation and DNA fragmentation. Methods in Enzymology, 322, 177-182
48. Deepak Nijhawan, Narimon Honarpour, and Xiaodong Wang (2000). Apoptosis in neural development and disease. Annual Review of Neuroscience. 23, 73-87
49. Imawati Budihardjo, Holt Oliver, Michael Lutter, Xu Luo, and Xiaodong Wang (1999). Biochemical pathways of caspases activation during apoptosis. Annual Review of Cell and Developmental Biology. 15, 269-290.
50. Antony Rodrigues, Holt Oliver, Hua Zou, Xiaodong Wang, and John M. Abrams (1999). Dark, a drosophila homolog of Apaf-1/Ced-4, functions in an evolutionarily conserved death pathway. Nature Cell Biol. 1, 272 - 279.
51. Cherie Purring, Hua Zou, Xiaodong Wang, and George McLendon (1999). Stoichiometry, free energy, and kinetic aspects of cytochrome c:Apaf-1 binding in apoptosis. J. Am. Chem. Soc.121, 7435-7436.
52. Xuesong Liu, Hua Zou, Piotr Widlak, William Garrard, and Xiaodong Wang (1999). Activation of the apoptotic endonuclease DFF40 (CAD/CPAN): oligomerization and direct interaction with histone H1. J. Biol. Chem. 274, 13836-13840.
53. Hua Zou, Yuchen Li, Xuesong Liu, and Xiaodong Wang (1999). An Apaf-1/cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J. Biol. Chem. 274, 11549-11556.
54. Jianhua Zhang, Xuesong Liu, David C. Scherer, Gregory P. Boivin, Luc Van Kaer, Xiaodong Wang, and Ming Xu (1998). Resistance to DNA fragmentation and normal development in mice lacking the DNA fragmentation factor 45. Proc. Natl. Acad. Sci. USA. 95, 12480-12485.
55. Xu Luo, Imawati Budihardjo, Hua Zou, Clive Slaughter, and Xiaodong Wang (1998). Bid, a Bcl-2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94, 481-490.
56. Lorenzo M. Leoni, Qi Chao, Howard B. Cottam, Davide Genini, Michael Rosenbach, Carlos J. Carrera, Imawati Budihardjo, Xiaodong Wang, and Dennis A. Carson (1998). Induction of an apoptotic program in cell free extracts by 2-chloro-2’-deoxyadenosine 5’-triphosphate (2CdATP) and cytochrome c. Proc. Natl. Acad. Sci. USA. 95, 9567-9571.
57. Xuesong Liu, Peng Li, Piotr Widlak, Hua Zou, Xu Luo, William T. Garrard, and Xiaodong Wang (1998). The 40-kDa subunit of DNA fragmentation factor induces DNA fragmentation and chromatin condensation during apoptosis. Proc. Natl. Acad. Sci. USA. 95, 8461-846.
58. Toh, S.Y., Wang, X.D., and Li, P. (1998). Identification of the nuclear factor HMG2 as an activator for DFF nuclease activity. BBRC. 250, 598-601.
59. Peng Li, Deepak Nijhawan, Imawati Budihardjo, Srinivasa M. Srinivasula, Manzoor Ahmad, Emad S. Alnemri, and Xiaodong Wang (1997). Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91, 479-489.
60. Kim, C. N., Wang, X., Huang, Y., Ibrado, A. M., Liu, L., Fang, G., and Bhalla, K. (1997). Overexpression of Bcl-X(L) inhibits Ara-C-induced mitochondrial loss of cytochrome c and other perturbations that activate the molecular cascade of apoptosis. Cancer Res. 57, 3115-3120.
61. Hua Zou, William J. Henzel, Xuesong Liu, Alexis Lutschg, and Xiaodong Wang. (1997) Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90, 405-413.
62. Xuesong Liu, Hua Zou, Clive Slaughter, and Xiaodong Wang. (1997). DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. Cell 89, 175-184.
63. Jie Yang, Xuesong Liu, Kapil Bhalla, Caryn Naekyung Kim, Ana Maria Ibrado, Jiyang Cai, Tsung-I Peng, Dean P. Jones and Xiaodong Wang. (1997). Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 275, 1129-1132.
64. Xuesong Liu, Caryn Naekyung Kim, Jie Yang, Ronald Jemmerson, and Xiaodong Wang (1996). Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86, 147-157.
65. Xuesong Liu, Caryn Naekyung Kim, Jan Pohl and Xiaodong Wang (1996). Purification and characterization of an interleukin-1?-converting enzyme family protease that activates cysteine protease P32 (CPP32). J. Biol. Chem. 271, 13371-13376.
66. Xiaodong Wang, Nikolai G. Zelenski, Jianxin Yang, Juro Sakai, Michael S. Brown, and Joseph L. Goldstein (1996). Cleavage of sterol regulatory element binding proteins (SREBPs) by CPP32 during apoptosis. EMBO J. 15, 1012-1020.
67. Xiaodong Wang, Jih-tung Pai, Elizabeth A. Wiedenfeld, Clive A. Slaughter, Julio Medina, Joseph L. Goldstein, and Michael S. Brown (1995). Purification of an ICE-related cysteine protease that cleaves sterol-regulatory element binding proteins between the leucine zipper and transmembrane domains. J. Biol. Chem. 270, 18044-18050.
68. Ryuichiro Sato, Jianxin Yang, Xiaodong Wang, Mark J. Evans, Y.K. Ho, Joseph L. Goldstein, and Michael S. Brown (1994). Assignment of the membrane attachment, DNA binding, and transcriptional activation domains of sterol regulatory element binding protein-1 (SREBP-1). J. Biol. Chem. 269, 17267-17273.
69. Xiaodong Wang, Ryuichiro Sato, Michael S. Brown, Xianxin Hua, and Joseph L. Goldstein (1994). SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell 77, 53-62.
70. Xianxin Hua, Chieko Yokoyama, Jian Wu, Michael R. Briggs, Michael S. Brown, Joseph L. Goldstein, and Xiaodong Wang (1993). SREBP-2, a second basic helix-loop-helix leucine zipper protein that stimulates transcription by binding to a sterol regulatory element. Proc. Natl. Acad. Sci. USA. 90, 11603-11607.
71. Chieko Yokoyama, Xiaodong Wang, Michael R. Briggs, Arie Admon, Jian Wu, Xianxin Hua, Joseph L. Goldstein, and Michael S. Brown (1993). SREBP-1, a basic helix-loop-helix leucine zipper protein that controls transcription of the LDL receptor gene. Cell 75, 187-197.
72. Xiaodong Wang, Michael R. Briggs, Xianxin Hua, Chieko Yokoyama, Joseph L. Goldstein, and Michael S. Brown (1993). Nuclear protein that binds sterol regulatory element of low-density lipoprotein receptor promotor II. Purification and characterization. J. Biol. Chem. 268, 14497-14504.
73. Michael R. Briggs, Chieko Yokoyama, Xiaodong Wang, Michael S. Brown, and Joseph L. Goldstein (1993). Nuclear protein that binds sterol regulatory element of low-density lipoprotein receptor promotor I. Identification of the protein and delineation of its target nucleotide sequence. J. Biol. Chem. 268, 14490-14496.
74. Xiaodong Wang and Richard A. Padgett (1989). Hydroxyl radical "footprinting" of RNA: application to pre-mRNA splicing complexes. Proc. Natl. Acad. Sci. USA. 86, 7795-7799.