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北京生命科学研究所   
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王晓东 博士 北京生命科学研究所所长、资深研究员 美国国家科学院院士 教育经历 1991 美国德克萨斯大学西南医学中心生物化学博士 Ph.D. Biochemistry, March 1991, University of Texas Southwestern Medical Center, Dallas, Texas, USA 1984 北京师范大学生物系学士 B.S. Biology, July 1984, Beijing Normal University, Beijing, China 工作经历 Professional Experience 2004 获美国科学院分子生物学奖，并当选美国国家科学院院士 NAS Award in Molecular Biology, elected to National Academy of Sciences, USA 2003- 北京生命科学研究所资深研究员 Investigator, National Institute of Biological Sciences,Beijing, China 2002- 霍华德-休斯医学研究所研究员 present Investigator, Howard Hughes Medical Institute. 2001- 美国德克萨斯大学西南医学中心生物医学科学杰出首席教授 present George L. MacGregor Distinguished Chair Professor in Biomedical Science, UT-Southwestern. 1999-2001 美国德克萨斯大学西南医学中心生物化学系副教授 Associate Professor, Department of Biochemistry, Universityof Texas Southwestern Medical Center at Dallas. 1997-2002 霍华德-休斯医学研究所助理研究员 Assistant Investigator, Howard Hughes Medical Institute. 1996-1999 美国德克萨斯大学西南医学中心生物化学系助理教授 Assistant Professor, Department of Biochemistry, Universityof Texas Southwestern Medical Center at Dallas. 1995-1996 Emory大学医学院生物化学系助理教授，从事哺乳动物细胞凋亡的生物化学途径的研究 Assistant Professor, Department of Biochemistry, Emory University School of Medicine, studies on the biochemical pathway of apoptosis in mammalian cells. 1991-1995 美国德克萨斯大学西南医学中心Joseph L. Goldstein and Michael S. Brown实验室进行博士后训练，从事基因表达的胆固醇调节的研究 Postdoctoral research with Drs. Joseph L. Goldstein and Michael S. Brown, UT-Southwestern, studies on sterol regulation of gene expression. 1986-1991 美国德克萨斯大学西南医学中心师从Richard A. Padgett攻读博士学位，从事研究哺乳动物前信使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 北京师范大学师从薛绍白教授撰写学士论文，研究哺乳动物细胞周期调控 Undergraduate thesis with Professor Shaobai Xue, BeijingNormal University. Studies on mammalian cell cycle control. AWARDS AND FELLOWSHIPS 2006 The Shaw Prize in Life Science and Medicine 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 ACTIVE RESEARCH SUPPORT Howard Hughes Medical Institute NIH RO1GM57158-07, National Institute of Health The Welch Foundation, I-1412 NCI Program Project Grant (Co-PI, P01 CA95471-02) Profession Membership AACR, American Association of Cancer Research American Society of Biochemistry and Molecular Biology American Society of Cell Biology Ray Wu Society SCBA, Society of Chinese Biomedical Scientist in America 研究概述 我们在北京生命科学研究所（NIBS）的研究目标是阐明细胞死亡的分子机理。我们相信这些知识将帮助我们理解现代社会中包括癌症、自身免疫疾病、心血管疾病以及神经退行性疾病等主要疾病的发病机理，并进而有助我们设计出相应的治疗策略。我们目前的研究是过去15年来对细胞凋亡，一种由细胞内的Caspases执行的细胞死亡形式的系统研究的延伸。这些研究经历使我们认识到细胞凋亡仅仅只是细胞自我灭亡的形式之一，另外还有一些细胞死亡的其它方式，它们通过与细胞凋亡相似而又不同的细胞内成份和调节机制来完成。这其中包括我们目前注意到的由肿瘤坏死因子受体诱发的细胞坏死。我们发现了一种在肿瘤坏死因子受体下游的激酶Rip3在这种细胞死亡形式中起着关键作用。我们正在研究Rip3是如何杀死细胞，以及这个过程与细胞凋亡以及其它形式的细胞死亡间有何联系。 我们实验室欢迎有兴趣的科学家加入到我们的队伍，来共同解决细胞死亡这个迷。除了我们擅长的生物化学技术，我们实验室也装备有分子生物学、细胞生物学、以及化学生物学等领域的最先进的工具和手段。 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).

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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-François 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 Å 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…).

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