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科學研究

王曉東博士

王曉東博士

北京生命科學研究所所長、資深研究員

美國國家科學院院士

中國科學院外籍院士

Xiaodong Wang, Ph.D.

Director and Investigator, NIBS, Beijing, China

Member of the National Academy of Sciences, USA

Foreign Member of the Chinese Academy of Sciences

Phone：010-80726688 Fax： 010-80726673

E-mail：wangxiaodong@nibs.ac.cn

工作經歷

Professional Experience

2003-	北京生命科學研究所所長、資深研究員
	Director and Investigator, National Institute of Biological Sciences, Beijing, China
2002-2010	霍華德-休斯醫學研究所研究員
	Investigator, Howard Hughes Medical Institute.
2001-2010	美國德克薩斯大學西南醫學中心生物醫學科學杰出首席教授
	George L. MacGregor Distinguished Chair Professor in Biomedical Science, UT-Southwestern.
1999-2001	美國德克薩斯大學西南醫學中心生物化學系副教授
	Associate Professor, Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas.
1997-2002	霍華德-休斯醫學研究所助理研究員
	Assistant Investigator, Howard Hughes Medical Institute.
1996-1999	美國德克薩斯大學西南醫學中心生物化學系助理教授
	Assistant Professor, Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas.
1995-1996	Emory大學醫學院生物化學系助理教授，從事哺乳動物細胞凋亡的生物化學途徑的研究
	Assistant Professor, Department of Biochemistry, Emory University School of Medicine, studies on the biochemical pathway of apoptosis in mammalian cells.
1991-1995	美國德克薩斯大學西南醫學中心Joseph L. Goldstein and Michael S. Brown實驗室進行博士后訓練，從事基因表達的膽固醇調節的研究
	Postdoctoral research with Drs. Joseph L. Goldstein and Michael S. Brown, UT-Southwestern, studies on sterol regulation of gene expression.
1986-1991	美國德克薩斯大學西南醫學中心師從Richard A. Padgett攻讀博士學位，從事研究哺乳動物前信使mRNA剪切的研究
	Ph.D.dissertation research with Dr. Richard A. Padgett, UT-Southwestern. Studies on mammalian pre-messenger RNA splicing.
1984-1985	北京師范大學師從薛紹白教授撰寫學士論文，研究哺乳動物細胞周期調控
	Undergraduate thesis with Professor Shaobai Xue, Beijing Normal University. Studies on mammalian cell cycle control.

AWARDS AND FELLOWSHIPS

2022 Honorary Ph.D. Hong Kong University of Science and Technology

2020 King Faisal Prize in Science, King Faisal Foundation, Saudi Arabia

2013 Outstanding Scientist Award, Qiu Shi Science and Technology Foundation, Hong Kong

2012 ASBMB-Merck Award, American Society of Biochemistry and Molecular Biology

2010 Honorary Ph.D. University of Macao

2007 Richard Lounsbery Award, the National Academy of Sciences, USA

2006 The Shaw Prize in Life Science and Medicine, The Shaw Prize Foundation, Hong Kong

2004 NAS Award in Molecular Biology, The National Academy of Sciences, USA

2004 Outstanding Achievement Award, American Association of Cancer Research

2003 Norman Hackerman Award, The Welch Foundation

2001 Paul Marks Prize, Memorial Sloan-Kettering Cancer Center

2000 Eli Lilly Award, American Chemical Society

2000 Schering-Plough Award, American Society of Biochemistry and Molecular Biology

1999 Young Investigator Award, Society of Chinese Biomedical Scientist in America

1998 Wilson S. Stone Memorial Award, MD-Anderson Cancer Center

1991 Damon Runyon-Walter Winchell Cancer Research Fund Postdoctoral Fellowship

1984 CUSBEA (Chinese-United States Biochemistry and Molecular Biology Examination and Application) Student

Profession Membership

National Academy of Sciences, USA
Chinese Academy of Sciences (Foreign Associate)
European Molecular Biology Organization (Foreign Associate)
Academy of AACR, American Association of Cancer Research
American Society of Biochemistry and Molecular Biology
American Society of Cell Biology
SCBA, Society of Bioscientists in America

研究概述

我們在北京生命科學研究所（NIBS）的研究目標是闡明細胞死亡的分子機理。我們相信這些知識將幫助我們理解現代社會中包括癌癥、自身免疫疾病、心血管疾病以及神經退行性疾病等主要疾病的發病機理，并進而有助我們設計出相應的治療策略。我們目前的研究是過去15年來對細胞凋亡，一種由細胞內的Caspases執行的細胞死亡形式的系統研究的延伸。這些研究經歷使我們認識到細胞凋亡僅僅只是細胞自我滅亡的形式之一，另外還有一些細胞死亡的其它方式，它們通過與細胞凋亡相似而又不同的細胞內成份和調節機制來完成。這其中包括我們目前注意到的由腫瘤壞死因子受體誘發的細胞壞死。我們發現了一種在腫瘤壞死因子受體下游的激酶Rip3在這種細胞死亡形式中起著關鍵作用。我們正在研究Rip3是如何殺死細胞，以及這個過程與細胞凋亡以及其它形式的細胞死亡間有何聯系。

我們實驗室歡迎有興趣的科學家加入到我們的隊伍，來共同解決細胞死亡這個迷。除了我們擅長的生物化學技術，我們實驗室也裝備有分子生物學、細胞生物學、以及化學生物學等領域的最先進的工具和手段。

The goal of our research laboratory at the National Institute of Biological Sciences (NIBS), Beijing is to understand cell death at molecular level. The research scope is an expansion of our previous 15 years of research focus on apoptosis, a form of cell death executed by intracellular caspases. These research experiences brought us to realization that apoptosis is only one form of self-disruptive cell death; and many forms of cell death share cellular components and regulators with apoptotic machinery. One form of cell death that recently brought to our attention is the tumor necrosis factor receptor induced cell death when caspases are inhibited. We discovered that a receptor interactive kinase, Rip3, is a critical downstream mediator for this form of cell death. We are in the process of studying how Rip3 kills a cell.

Publications

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. Xuesong Liu, Caryn Naekyung Kim, Jan Pohl and Xiaodong Wang (1996). Purification and characterization of an interleukin-1b-converting enzyme family protease that activates cysteine protease P32 (CPP32). J. Biol. Chem. 271, 13371-13376.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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’-deoxyadenosine5’-triphosphate (2CdATP) and cytochrome c. Proc. Natl. Acad. Sci. USA. 95, 9567-9571.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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 AC S 121, 7435-7436.

24. 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.

25. 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.

26. 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.

27. 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.

28. 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.

29. 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.

30. 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.

31. 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.

32. 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.

33. 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.

34. 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.

35. 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.

36. 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.

37. Lily Y. Li, Xu Luo, and Xiaodong Wang (2001) Endonuclease G (EndoG) is an apoptotic DNase when released from Mitochondria. Nature 412, 95-99.

38. 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.

39. 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.

40. 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.

41. 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.

42. 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.

43. 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.

44. 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.

45. 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.

46. 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-a in a death Regulatory Pathway. Science 299, 223-226.

47. 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.

48. Qinghua Liu, Tim A. Rand, Savitha Kalidas, Fenghe Du, Hyun-Eui Kim, Dean P. Smith and CONTACT _Con-46073E1D1 \c \s \l XiaodongWang (2003). R2D2, a bridge between the initiation and effector steps of the Drosophila RNAi pathway. Science 301, 1921-1925.

49. 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.

50. Lin Li, Ranny Mathew Thomas, Hidetaka Suzuki, Jef K. DeBrabander, CONTACT _Con-46073E1D1 \c \s \l Xiaodong Wang, and Patrick G. Harran (2004). A small molecule Smac mimic potentiates Trail- and TNFa-mediated cell death. Science 305, 1471-1474.

51. Tim A. Rand, Krzysztof Ginalski, Nick V. Grishin, and Xiaodong Wang (2004)

Biochemical identification of Argonaute 2 as the sole protein required for RNA-induced silencing complex activity. Proc. Natl. Acad. Sci. USA 101: 14385-14389.

52. Zhenyue Hao, Gordon Duncan, Chia-Che Chang, Andre Elia, Min Fang, Andrew Wakeham, Hitoshi okada, Thomas Calzascia, Yingju Jang, Annick You-Ten, Wen-Chen Yeh, Pamela Ohashi, Xiaodong Wang, and Tak Mak (2005). Specific ablation of the apoptotic function of cytochrome c in mice leads to neuronal hyperplasia and impaired lymphocyte homeostasis. Cell 121, 579-591.

53. Qing Zhong, Wenhua Gao, Fenghe Du, and CONTACT _Con-46073E1D1 \c \s \l 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.

54. Tim Rand, Sean Petersen, Fenghe Du, and Xiaodong Wang (2005). Argonaute 2 cleaves the anti-guide strand of siRNA during RISC activation. Cell 123, 621-629.

55. Hyun-Eui Kim, Fenghe Du, Min Fang, and Xiaodong Wang (2005). Formation of apoptosome is initiated by cytochrome c induced deoxyATP hydrolysis and subsequent nucleotide exchange on Apaf-1. Proc. Natl. Acad. Sci. USA. 102, 17545-17550.

56. Xinchao Yu, Devrim Acehan, Jean-Fran?ois Ménétret, Christopher R. Booth, Steven J. Ludtke, Stefan J. Riedl, Yigong Shi, Xiaodong Wang, and Christopher W. Akey (2005) A Structure of the human apoptosome at 12.8 ? resolution provides insights into this cell death platform. Structure (Camb) 13, 1725-1735.

57. Xinchao Yu, Lai Wang , Devrim Acehan, Xiaodong Wang, and Christopher W. Akey (2006). Three-dimensional structure of a double apoptosome formed by the drosophila Apaf-1 related killer. J. Mol. Biol. 355, 577-589.

58. Noelle S. Williams, Anthony W. G. Burgett, Ashley S. Atkins, Xiaodong Wang, Patrick G. Harran, and Steven L. McKnight (2007) Therapeutic Anti-Cancer Efficacy of a Synthetic Diazonamide Analog in the Absence of Overt Toxicity. Proc. Natl. Acad. Sci. USA 104, 2074-2079.

59. Gelin Wang, Libin Shang, Anthony W.G. Burgett, Patrick G. Harran and Xiaodong Wang (2007). Diazonamide Toxins Reveal an Unexpected Function for Ornithine ?-Amino Transferase in Mitotic Cell Division. Proc. Natl. Acad. Sci. USA 104, 2068-2073.

60. Sean L. Petersen,Lai Wang, Asligul Yalcin-Chin, Lin Li, Michael Peyton, John Minna, Patrick G. Harran and Xiaodong Wang (2007). Autocrine TNF alpha signaling renders human cancer cells susceptible to Smac mimetic induced apoptosis. Cancer Cell 12, 445-456.

61. Hyun-Eui Kim, Xuejun Jiang, Fenghe Du, and Xiaodong Wang (2008). PHAPI, CAS, and Hsp70 Promote Apoptosome Formation by Preventing Cytochrome c-induced Apaf-1 Aggregation and Enhancing Nucleotide Exchange on Apaf-1. Mol. Cell 30, 239-247.

62. Lai Wang, Fenghe Du, and Xiaodong Wang (2008). TNF-? induces two distinct caspase-8 activation pathways. Cell 133, 693-703.

63. Sudan He, Lai Wang, Lin Miao, Tao Wang, Fenghe Du, Liping Zhao, and Xiaodong Wang(2009) Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 137, 1100-1111.

64. Petersen SL, Michael Peyton, John D.Minna, Xiaodong Wang (2010). Overcoming cancer cell resistance to Smac mimetic induced apoptosis by modulating cIAP-2 expression. Proc. Natl. Acad. Sci. USA 107, 11936-11941.

65. Min Fang, Zhirong Shen, Song Huang, Liping Zhao, She Chen, Tak W. Mak and Xiaodong Wang (2010) The ER UDPase ENTPD5 promotes protein N-Glycosylation, the Warburg effect, and proliferation in the PTEN pathway. Cell 143, 711-724.

66. 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.

67. 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.

68. 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.

69. 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, and Xiaodong Wang (2013). Small-molecule activation of the TRAIL receptor DR5 inhuman cancer cells. Nature Chem. Biol. 9, 84–89

70. Wang H, Sun L, Su L, Rizo J, Liu L, Wang LF, Wang FS, and Wang X, Mixed Lineage Kinase Domain-like Protein MLKL Causes Necrotic Membrane Disruption upon Phosphorylation by RIP3

Molecular Cell, DOI: 10.1016/j.molcel.2014.03.003, Apr. 10, 2014

71. 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.

72. 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.

73. Xian Jiang, Li Li, Zhengxin Ying, Chenjie Pan, Shaoqiang Huang, Lin Li, Miaomiao Dai, Bo Yan, Ming Li, Hui Jiang, She Chen, Zhiyuan Zhang, Xiaodong Wang.A Small Molecule That Protects the Integrity of the Electron Transfer Chain Blocks the Mitochondrial Apoptotic Pathway .Molecular Cell, DOI: http://dx.doi.org/10.1016/j.molcel.2016.06.016, July 21, 2016

74. Li Li,Xian Jiang,Shaoqiang Huang,Zhengxin Ying, Zhaolan Zhang, Chenjie Pan,Sisi Li, Xiaodong Wang, Zhiyuan Zhang.Discovery of Highly Potent 2? Sulfonyl-Pyrimidinyl Derivatives for Apoptosis Inhibition and Ischemia Treatment.ACS Medicinal Chemistry Letter,DOI:10.1021/acsmedchemlett.6b00489, March 1,2017

75. Bo Yan, Lei Liu, Shaoqiang Huang, Yan Ren, Huayi Wang, Zhenglin Yao, Lin Li, She Chen, Xiaodong Wang and Zhiyuan Zhang.Discovery of a new class of highly potent necroptosis inhibitors targeting the mixed lineage kinase domain-like protein.Chem. Commun., DOI: 10.1039/c7cc00667e, April 4, 2017

76. Dianrong Li, LingjunMeng, Tao Xu, YaningSu, Xiao Liu, Zhiyuan Zhang,Xiaodong Wang.RIPK1-RIPK3-MLKL-dependent necrosis promotes the aging of mouse male reproductive system.eLife, DOI: 10.7554/eLife.27692, August 15,2017

77. Ying Z, Pan C, Shao T, Liu L, Li L, Guo D, Zhang S, Yuan T, Cao R, Jiang Z, Chen S, Wang F, Wang X.Mixed Lineage Kinase Domain-like Protein MLKL Breaks Down Myelin following Nerve Injury.Molecular cell, DOI：10.1016/j.molcel.2018.09.011, Oct. 18, 2018

78. Sitao Zhang S, Yaning Su, Zhengxin Ying, Dejia Guo, Chenjie Pan, Jia Guo, Ziye Zou, Lei Wang, Ze Zhang, Zhaodi Jiang, Zhiyuan Zhang, and Xiaodong Wang (2019).RIP1 kinase inhibitor halts the progression of an immune-induced demyelination disease at the stage of monocyte elevation.Proc. Natl. Acad. Sci. USA 116:5675-5680. doi: 10.1073.

79. Ran Cao, Li Li, Zhengxin Ying, Zichen Cao, Yongfen ma, Xiaoxu Mao, Jiaojiao Li, Xiangbing Qi, Zhiyuan Zhang, and Xiaodong Wang (2019).A small molecule protects mitochondrial integrity by inhibiting mTOR activity.Proc. Natl. Acad. Sci. USA 116:23332-23338. doi: 10.1073/pnas.1911246116.

80. Dianrong Li, Jie Chen, Youwei Ai, Xiaoqiong Gu, Li Li, Di Che, Zhaodi Jiang, Lin Li, She Chen, Huangwei Huang, Jiawen Wang, Tao Cai, Yang Cao, Xingbin Qi, and Xiaodong Wang (2019).Estrogen-related hormones induce apoptosis by stabilizing Schlafen-12 protein turnover.Mol. Cell 75, 1103-1116.

81. Dianrong Li, Youwei Ai, Jia Guo, Baijun Dong, Lin Li, Gaihong Cai, She Chen, Dan Xu, Fengchao Wang, and Xiaodong Wang (2020).Casein kinase 1G2 suppresses necroptosis- promoted testis aging by inhibiting receptor-interacting kinase 3.eLife 9: e61564 doi: 10.7554/eLife.61564

82. Bo Yan, Youwei Ai, Ze Zhang, Qi Sun, Yan Ma, Zhiyuan Zhang and Xiaodong Wang (2020).Membrane damage during ferroptosis is caused by oxidation of phospholipids catalyzed by the oxidoreductases POR and CYB5R1.Mol. Cell Dec 8; S1097-2765(20)30802-9. doi: 10.1016/j.molcel.2020.11.024.

Invited review article

1. 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.

2. Deepak Nijhawan, Narimon Honarpour, and Xiaodong Wang (2000). Apoptosis in neural development and disease. Annual Review of Neuroscience. 23, 73-87.

3. Xuesong Liu and Xiaodong Wang (2000). In vitro assays for caspase-3 activation and DNA fragmentation. Methods in Enzymology, 322, 177-182.

4. Xiaodong Wang (2001). The expanding role of mitochondria in apoptosis. Genes & Dev. 15, 2922-2933.

5. Xuejun Jiang and CONTACT _Con-46073E1D1 \c \s \l Xiaodong Wang (2004). Cytochrome c-mediated apoptosis. Annual Review of Biochemistry. 73, 87-106.

6. Peng Li, Deepak Nijhawan, and Xiaodong Wang (2004). Mitochondrial activation of apoptosis. Cell 116, S57-59.

Other Activities

Consultant, Idun Pharmaceuticals (7/15/98-7/15/2002)

Consultant, Sirna Therapeutics (3/06-1/07)

Co-founder and consultant, Joyant Pharmaceuticals (1/05-)

The founding Co-Director, National Institute of Biological Sciences, Beijing (1/03-)

Co-founder and Chair of Scientific Advisory Board (1/11-)

Member of Editorial Boards: Neoplasia (April, 1999- ); JBC (July 2002…); MBC (May 18, 2002…).

Patents

1. M.R. Briggs, M.S. Brown, J.L. Goldstein & X. Wang

SRE BINDING PROTEIN AND ASSAYS. U.S. Patent Number: 5,498,696 (Issued3/12/96).

2. J.L. Goldstein, M.S. Brown, M.R. Briggs & X. Wang

METHODS AND COMPOSITIONS RELATING TO STEROL REGULATORY ELEMENT BINDING PROTEINS. U.S. Patent Number: 5,527,690 (Issued6/18/96).

3. J.L. Goldstein, M.S. Brown, M.R. Briggs & X. Wang Methods relating to sterol regulatory element binding proteins. U.S. Patent 5,891,631 (Issued4/6/99).

4. Chunying Du & X. Wang

Activators of Caspases. U.S. Patent Number: 6,110,691 (Issued8/29/00)

5. Xuesong Liu and Xiaodong Wang

DNA Fragmentation Factor Involved in Chromatin Condensation and Fragmentation During Apoptosis. U.S. Patent Number: 6,165,737 (Issued12/26/00).

6. Xuesong Liu and X. Wang

DNA fragmentation factor. U.S. Patent Number: 6,515,118 (issued2/4/03)

7. Xiaodong Wang

APAF-1, an activator of caspase-3. U.S. Patent Number: 6,346,607 (Issued2/12/02).

8. Xiaodong Wang and Chunying Du

Apoptotic Compounds. U.S. Patent Number: 6,608,026 (Issued8/19/03).

9. CONTACT _Con-46073E1D1 \c \s \l Xiaodong Wang and Xuesong Liu

Regulation of apoptosis and in vitro model for studies thereof. U.S. Patent Number: 6,558,900 (Issued5/6/03).

10. Patrick G. Harran, Xiaodong Wang, K. De Brabander, Lin Li, Ranny Mathew Thomas, and Hidetaka Suzuki

Dimeric small molecule potentiators of apoptosis. U.S. Patent Number: 7,309,792 B2 (Issued12/18/2007).

11. CONTACT _Con-46073E1D1 \c \s \l Xiaodong Wang, Qing Zhong, Wenhua Gao, and Fenghe Du.

Mule: Mcl-1 ubiquitination ligase E3. U.S. Patent Number 7,303,887 B2 (Issued12/4/07).