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Hong-gang Wang
Title Professor
Institution College of Medicine
Department Pharmacology
Address 500 University Drive Hershey PA 17033
Mailbox: CH74
Telephone 7175314574
Email
Background
PREFERRED TITLE/ROLE:

Lois High Berstler Professor of Pharmacology

SECONDARY APPOINTMENT(S)/ INSTITUTE(S)/ CENTER(S):

Penn State Hershey Cancer Institute, The Huck Institutes of the Life Sciences

GRADUATE PROGRAM AFFILIATIONS:

Cell and Molecular Biology, Pharmacology, Biomedical Sciences: Translation Therapeutics Option, Integrative Biosciences: Molecular Medicine

EDUCATION:

B.S., University of Tsukuba, 1987
Ph.D., University of Tsukuba, 1992
Postdoctoral Training, Burnham Institute, 1993-1998

NARRATIVE:

Research in my laboratory is concerned with understanding the fundamental mechanisms that control apoptosis and autophagy in the context of oncogenesis. Drug discovery through the development of small molecules that directly target the molecular components of apoptosis and autophagy is another major interest of our research. Apoptosis (self-killing) is the most well defined form of physiological cell death and has long been used as a synonym for programmed cell death. In contrast, autophagy (self-eating) is a lysosomal degradation pathway and is generally thought to be a cytoprotective mechanism. However, mounting evidence also suggests that autophagy may contribute to cell death under certain circumstances. Although extensive crosstalk clearly exists between apoptosis and autophagy, the regulators that govern this crosstalk remain far from clear. Our recent studies suggest that the formation of an intracellular death-inducing signaling complex (iDISC) on the autophagosomal membrane is able to switch autophagy from pro-survival to pro-apoptosis. Moreover, my laboratory has cloned and characterized a member of the endophilin family, Bif-1, also known as endophilin B1 or SH3GLB1, as a novel Bax activator and autophagy modulator. We have demonstrated that the loss of Bif-1 not only suppresses Bax-mediated mitochondrial apoptosis but also impairs autophagy. Bif-1 interacts with Beclin1 through UVRAG and regulates autophagosome formation and Atg9 trafficking possibly through the mediation of Golgi fragmentation. Importantly, the expression of Bif-1 is lost or decreased in various human cancers, and the deletion of Bif-1 promotes tumor development in mouse models. Currently, we are exploring the precise mechanisms underlying Bif-1-mediated apoptosis and autophagy to better understand how Bif-1 functions as a tumor suppressor. In addition, our group was among the first to link AMPK, a cellular energy sensor, to ULK1, a key initiator of autophagy, in the regulation of mammalian autophagy. Furthermore, my laboratory has been collaborating with medicinal chemists during the past decade for the development and characterization of Bcl-2 family inhibitors as novel anticancer agents. For example, we have recently identified a novel selective small-molecule Mcl-1 inhibitor (maritoclax) that antagonizes Mcl-1 and overcomes ABT-737 resistance by directly binding to and targeting Mcl-1 for proteasomal degradation. The ultimate goal of my laboratory is to translate basic science research discoveries to the development of new approaches for the prevention and treatment of cancer.
Publications
1. Yang Y, Fiskus W, Yong B, Atadja P, Takahashi Y, Pandita TK, Wang HG, Bhalla KN. Acetylated hsp70 and KAP1-mediated Vps34 SUMOylation is required for autophagosome creation in autophagy. Proc Natl Acad Sci U S A. 2013 Apr 23; 110(17):6841-6.
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2. Takahashi Y, Hori T, Cooper TK, Liao J, Desai N, Serfass JM, Young MM, Park S, Izu Y, Wang HG. Bif-1 haploinsufficiency promotes chromosomal instability and accelerates Myc-driven lymphomagenesis via suppression of mitophagy. Blood. 2013 Feb 28; 121(9):1622-32.
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3. Takahashi Y, Young MM, Wang HG. SNAPping off Golgi membranes for autophagosome formation. Cell Cycle. 2013 Jan 1; 12(1):15-6.
  View in: PubMed
 
4. Young MM, Kester M, Wang HG. Sphingolipids: regulators of crosstalk between apoptosis and autophagy. J Lipid Res. 2013 Jan; 54(1):5-19.
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5. Liu Q, Wang HG. Anti-cancer drug discovery and development: Bcl-2 family small molecule inhibitors. Commun Integr Biol. 2012 Nov 1; 5(6):557-65.
  View in: PubMed
 
6. Muppidi A, Doi K, Edwardraja S, Drake EJ, Gulick AM, Wang HG, Lin Q. Rational design of proteolytically stable, cell-permeable peptide-based selective Mcl-1 inhibitors. J Am Chem Soc. 2012 Sep 12; 134(36):14734-7.
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7. Ren T, Dong W, Takahashi Y, Xiang D, Yuan Y, Liu X, Loughran TP, Sun SC, Wang HG, Cheng H. HTLV-2 Tax immortalizes human CD4+ memory T lymphocytes by oncogenic activation and dysregulation of autophagy. J Biol Chem. 2012 Oct 5; 287(41):34683-93.
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8. Runkle KB, Meyerkord CL, Desai NV, Takahashi Y, Wang HG. Bif-1 suppresses breast cancer cell migration by promoting EGFR endocytic degradation. Cancer Biol Ther. 2012 Aug; 13(10):956-66.
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9. Kim YB, Balasis ME, Doi K, Berndt N, DuBoulay C, Hu CC, Guida W, Wang HG, Sebti SM, Del Valle JR. Synthesis and evaluation of substituted hexahydronaphthalenes as novel inhibitors of the Mcl-1/BimBH3 interaction. Bioorg Med Chem Lett. 2012 Sep 15; 22(18):5961-5.
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10. Young MM, Takahashi Y, Khan O, Park S, Hori T, Yun J, Sharma AK, Amin S, Hu CD, Zhang J, Kester M, Wang HG. Autophagosomal membrane serves as platform for intracellular death-inducing signaling complex (iDISC)-mediated caspase-8 activation and apoptosis. J Biol Chem. 2012 Apr 6; 287(15):12455-68.
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11. Doi K, Li R, Sung SS, Wu H, Liu Y, Manieri W, Krishnegowda G, Awwad A, Dewey A, Liu X, Amin S, Cheng C, Qin Y, Schonbrunn E, Daughdrill G, Loughran TP, Sebti S, Wang HG. Discovery of marinopyrrole A (maritoclax) as a selective Mcl-1 antagonist that overcomes ABT-737 resistance by binding to and targeting Mcl-1 for proteasomal degradation. J Biol Chem. 2012 Mar 23; 287(13):10224-35.
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12. Watters RJ, Wang HG, Sung SS, Loughran TP, Liu X. Targeting sphingosine-1-phosphate receptors in cancer. Anticancer Agents Med Chem. 2011 Nov; 11(9):810-7.
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13. Zhang Y, Cheng Y, Zhang L, Ren X, Huber-Keener KJ, Lee S, Yun J, Wang HG, Yang JM. Inhibition of eEF-2 kinase sensitizes human glioma cells to TRAIL and down-regulates Bcl-xL expression. Biochem Biophys Res Commun. 2011 Oct 14; 414(1):129-34.
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14. Liao A, Broeg K, Fox T, Tan SF, Watters R, Shah MV, Zhang LQ, Li Y, Ryland L, Yang J, Aliaga C, Dewey A, Rogers A, Loughran K, Hirsch L, Jarbadan NR, Baab KT, Liao J, Wang HG, Kester M, Desai D, Amin S, Loughran TP, Liu X. Therapeutic efficacy of FTY720 in a rat model of NK-cell leukemia. Blood. 2011 Sep 8; 118(10):2793-800.
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15. Kulkarni SS, Hu X, Doi K, Wang HG, Manetsch R. Screening of protein-protein interaction modulators via sulfo-click kinetic target-guided synthesis. ACS Chem Biol. 2011 Jul 15; 6(7):724-32.
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16. Coppola D, Helm J, Ghayouri M, Malafa MP, Wang HG. Down-regulation of Bax-interacting factor 1 in human pancreatic ductal adenocarcinoma. Pancreas. 2011 Apr; 40(3):433-7.
  View in: PubMed
 
17. Takahashi Y, Meyerkord CL, Hori T, Runkle K, Fox TE, Kester M, Loughran TP, Wang HG. Bif-1 regulates Atg9 trafficking by mediating the fission of Golgi membranes during autophagy. Autophagy. 2011 Jan; 7(1):61-73.
  View in: PubMed
 
18. Kazi A, Sun J, Doi K, Sung SS, Takahashi Y, Yin H, Rodriguez JM, Becerril J, Berndt N, Hamilton AD, Wang HG, Sebti SM. The BH3 alpha-helical mimic BH3-M6 disrupts Bcl-X(L), Bcl-2, and MCL-1 protein-protein interactions with Bax, Bak, Bad, or Bim and induces apoptosis in a Bax- and Bim-dependent manner. J Biol Chem. 2011 Mar 18; 286(11):9382-92.
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19. Lee JW, Park S, Takahashi Y, Wang HG. The association of AMPK with ULK1 regulates autophagy. PLoS One. 2010; 5(11):e15394.
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20. Yang J, Takahashi Y, Cheng E, Liu J, Terranova PF, Zhao B, Thrasher JB, Wang HG, Li B. GSK-3beta promotes cell survival by modulating Bif-1-dependent autophagy and cell death. J Cell Sci. 2010 Mar 15; 123(Pt 6):861-70.
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21. Nair RR, Emmons MF, Cress AE, Argilagos RF, Lam K, Kerr WT, Wang HG, Dalton WS, Hazlehurst LA. HYD1-induced increase in reactive oxygen species leads to autophagy and necrotic cell death in multiple myeloma cells. Mol Cancer Ther. 2009 Aug; 8(8):2441-51.
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22. Wei J, Kitada S, Rega MF, Emdadi A, Yuan H, Cellitti J, Stebbins JL, Zhai D, Sun J, Yang L, Dahl R, Zhang Z, Wu B, Wang S, Reed TA, Wang HG, Lawrence N, Sebti S, Reed JC, Pellecchia M. Apogossypol derivatives as antagonists of antiapoptotic Bcl-2 family proteins. Mol Cancer Ther. 2009 Apr; 8(4):904-13.
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23. Takahashi Y, Meyerkord CL, Wang HG. Bif-1/endophilin B1: a candidate for crescent driving force in autophagy. Cell Death Differ. 2009 Jul; 16(7):947-55.
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24. Yamaguchi H, Woods NT, Piluso LG, Lee HH, Chen J, Bhalla KN, Monteiro A, Liu X, Hung MC, Wang HG. p53 acetylation is crucial for its transcription-independent proapoptotic functions. J Biol Chem. 2009 Apr 24; 284(17):11171-83.
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25. Etxebarria A, Terrones O, Yamaguchi H, Landajuela A, Landeta O, Antonsson B, Wang HG, Basañez G. Endophilin B1/Bif-1 stimulates BAX activation independently from its capacity to produce large scale membrane morphological rearrangements. J Biol Chem. 2009 Feb 13; 284(7):4200-12.
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26. Coppola D, Khalil F, Eschrich SA, Boulware D, Yeatman T, Wang HG. Down-regulation of Bax-interacting factor-1 in colorectal adenocarcinoma. Cancer. 2008 Nov 15; 113(10):2665-70.
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27. Hu X, Sun J, Wang HG, Manetsch R. Bcl-XL-templated assembly of its own protein-protein interaction modulator from fragments decorated with thio acids and sulfonyl azides. J Am Chem Soc. 2008 Oct 22; 130(42):13820-1.
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28. Meyerkord CL, Takahashi Y, Araya R, Takada N, Weiss RS, Wang HG. Loss of Hus1 sensitizes cells to etoposide-induced apoptosis by regulating BH3-only proteins. Oncogene. 2008 Dec 11; 27(58):7248-59.
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29. Coppola D, Oliveri C, Sayegh Z, Boulware D, Takahashi Y, Pow-Sang J, Djeu JY, Wang HG. Bax-interacting factor-1 expression in prostate cancer. Clin Genitourin Cancer. 2008 Sep; 6(2):117-21.
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30. Li CG, Gruidl M, Eschrich S, McCarthy S, Wang HG, Alexandrow MG, Yeatman TJ. Insig2 is associated with colon tumorigenesis and inhibits Bax-mediated apoptosis. Int J Cancer. 2008 Jul 15; 123(2):273-82.
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31. Yamaguchi H, Woods NT, Dorsey JF, Takahashi Y, Gjertsen NR, Yeatman T, Wu J, Wang HG. SRC directly phosphorylates Bif-1 and prevents its interaction with Bax and the initiation of anoikis. J Biol Chem. 2008 Jul 4; 283(27):19112-8.
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32. Oliveira V, Romanow WJ, Geisen C, Otterness DM, Mercurio F, Wang HG, Dalton WS, Abraham RT. A protective role for the human SMG-1 kinase against tumor necrosis factor-alpha-induced apoptosis. J Biol Chem. 2008 May 9; 283(19):13174-84.
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33. Sun A, Tang J, Hong Y, Song J, Terranova PF, Thrasher JB, Svojanovsky S, Wang HG, Li B. Androgen receptor-dependent regulation of Bcl-xL expression: Implication in prostate cancer progression. Prostate. 2008 Mar 1; 68(4):453-61.
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34. Klionsky DJ, Abeliovich H, Agostinis P, Agrawal DK, Aliev G, Askew DS, Baba M, Baehrecke EH, Bahr BA, Ballabio A, Bamber BA, Bassham DC, Bergamini E, Bi X, Biard-Piechaczyk M, Blum JS, Bredesen DE, Brodsky JL, Brumell JH, Brunk UT, Bursch W, Camougrand N, Cebollero E, Cecconi F, Chen Y, Chin LS, Choi A, Chu CT, Chung J, Clarke PG, Clark RS, Clarke SG, Clavé C, Cleveland JL, Codogno P, Colombo MI, Coto-Montes A, Cregg JM, Cuervo AM, Debnath J, Demarchi F, Dennis PB, Dennis PA, Deretic V, Devenish RJ, Di Sano F, Dice JF, Difiglia M, Dinesh-Kumar S, Distelhorst CW, Djavaheri-Mergny M, Dorsey FC, Dröge W, Dron M, Dunn WA, Duszenko M, Eissa NT, Elazar Z, Esclatine A, Eskelinen EL, Fésüs L, Finley KD, Fuentes JM, Fueyo J, Fujisaki K, Galliot B, Gao FB, Gewirtz DA, Gibson SB, Gohla A, Goldberg AL, Gonzalez R, González-Estévez C, Gorski S, Gottlieb RA, Häussinger D, He YW, Heidenreich K, Hill JA, Høyer-Hansen M, Hu X, Huang WP, Iwasaki A, Jäättelä M, Jackson WT, Jiang X, Jin S, Johansen T, Jung JU, Kadowaki M, Kang C, Kelekar A, Kessel DH, Kiel JA, Kim HP, Kimchi A, Kinsella TJ, Kiselyov K, Kitamoto K, Knecht E, Komatsu M, Kominami E, Kondo S, Kovács AL, Kroemer G, Kuan CY, Kumar R, Kundu M, Landry J, Laporte M, Le W, Lei HY, Lenardo MJ, Levine B, Lieberman A, Lim KL, Lin FC, Liou W, Liu LF, Lopez-Berestein G, López-Otín C, Lu B, Macleod KF, Malorni W, Martinet W, Matsuoka K, Mautner J, Meijer AJ, Meléndez A, Michels P, Miotto G, Mistiaen WP, Mizushima N, Mograbi B, Monastyrska I, Moore MN, Moreira PI, Moriyasu Y, Motyl T, Münz C, Murphy LO, Naqvi NI, Neufeld TP, Nishino I, Nixon RA, Noda T, Nürnberg B, Ogawa M, Oleinick NL, Olsen LJ, Ozpolat B, Paglin S, Palmer GE, Papassideri I, Parkes M, Perlmutter DH, Perry G, Piacentini M, Pinkas-Kramarski R, Prescott M, Proikas-Cezanne T, Raben N, Rami A, Reggiori F, Rohrer B, Rubinsztein DC, Ryan KM, Sadoshima J, Sakagami H, Sakai Y, Sandri M, Sasakawa C, Sass M, Schneider C, Seglen PO, Seleverstov O, Settleman J, Shacka JJ, Shapiro IM, Sibirny A, Silva-Zacarin EC, Simon HU, Simone C, Simonsen A, Smith MA, Spanel-Borowski K, Srinivas V, Steeves M, Stenmark H, Stromhaug PE, Subauste CS, Sugimoto S, Sulzer D, Suzuki T, Swanson MS, Tabas I, Takeshita F, Talbot NJ, Tallóczy Z, Tanaka K, Tanaka K, Tanida I, Taylor GS, Taylor JP, Terman A, Tettamanti G, Thompson CB, Thumm M, Tolkovsky AM, Tooze SA, Truant R, Tumanovska LV, Uchiyama Y, Ueno T, Uzcátegui NL, van der Klei I, Vaquero EC, Vellai T, Vogel MW, Wang HG, Webster P, Wiley JW, Xi Z, Xiao G, Yahalom J, Yang JM, Yap G, Yin XM, Yoshimori T, Yu L, Yue Z, Yuzaki M, Zabirnyk O, Zheng X, Zhu X, Deter RL. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy. 2008 Feb; 4(2):151-75.
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35. Woods NT, Yamaguchi H, Lee FY, Bhalla KN, Wang HG. Anoikis, initiated by Mcl-1 degradation and Bim induction, is deregulated during oncogenesis. Cancer Res. 2007 Nov 15; 67(22):10744-52.
  View in: PubMed
 
36. Takahashi Y, Meyerkord CL, Wang HG. BARgaining membranes for autophagosome formation: Regulation of autophagy and tumorigenesis by Bif-1/Endophilin B1. Autophagy. 2008 Jan; 4(1):121-4.
  View in: PubMed
 
37. Vicente-Suarez I, Takahashi Y, Cheng F, Horna P, Wang HW, Wang HG, Sotomayor EM. Identification of a novel negative role of flagellin in regulating IL-10 production. Eur J Immunol. 2007 Nov; 37(11):3164-75.
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38. Ren Y, Chen Z, Chen L, Woods NT, Reuther GW, Cheng JQ, Wang HG, Wu J. Shp2E76K mutant confers cytokine-independent survival of TF-1 myeloid cells by up-regulating Bcl-XL. J Biol Chem. 2007 Dec 14; 282(50):36463-73.
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39. Takahashi Y, Coppola D, Matsushita N, Cualing HD, Sun M, Sato Y, Liang C, Jung JU, Cheng JQ, Mulé JJ, Pledger WJ, Wang HG. Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nat Cell Biol. 2007 Oct; 9(10):1142-51.
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40. Azumi K, Sabau SV, Fujie M, Usami T, Koyanagi R, Kawashima T, Fujiwara S, Ogasawara M, Satake M, Nonaka M, Wang HG, Satou Y, Satoh N. Gene expression profile during the life cycle of the urochordate Ciona intestinalis. Dev Biol. 2007 Aug 15; 308(2):572-82.
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41. Yamaguchi H, Wang HG. Tissue transglutaminase serves as an inhibitor of apoptosis by cross-linking caspase 3 in thapsigargin-treated cells. Mol Cell Biol. 2006 Jan; 26(2):569-79.
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42. Takada N, Yamaguchi H, Shida K, Terajima D, Satou Y, Kasuya A, Satoh N, Satake M, Wang HG. The cell death machinery controlled by Bax and Bcl-XL is evolutionarily conserved in Ciona intestinalis. Apoptosis. 2005 Dec; 10(6):1211-20.
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43. Takahashi Y, Karbowski M, Yamaguchi H, Kazi A, Wu J, Sebti SM, Youle RJ, Wang HG. Loss of Bif-1 suppresses Bax/Bak conformational change and mitochondrial apoptosis. Mol Cell Biol. 2005 Nov; 25(21):9369-82.
  View in: PubMed
 
44. Bali P, Pranpat M, Swaby R, Fiskus W, Yamaguchi H, Balasis M, Rocha K, Wang HG, Richon V, Bhalla K. Activity of suberoylanilide hydroxamic Acid against human breast cancer cells with amplification of her-2. Clin Cancer Res. 2005 Sep 1; 11(17):6382-9.
  View in: PubMed
 
45. Zhang X, Li P, Bao J, Nicosia SV, Wang H, Enkemann SA, Bai W. Suppression of death receptor-mediated apoptosis by 1,25-dihydroxyvitamin D3 revealed by microarray analysis. J Biol Chem. 2005 Oct 21; 280(42):35458-68.
  View in: PubMed
 
46. Yin H, Lee GI, Sedey KA, Kutzki O, Park HS, Orner BP, Ernst JT, Wang HG, Sebti SM, Hamilton AD. Terphenyl-Based Bak BH3 alpha-helical proteomimetics as low-molecular-weight antagonists of Bcl-xL. J Am Chem Soc. 2005 Jul 27; 127(29):10191-6.
  View in: PubMed
 
47. Zheng Y, Yamaguchi H, Tian C, Lee MW, Tang H, Wang HG, Chen Q. Arsenic trioxide (As(2)O(3)) induces apoptosis through activation of Bax in hematopoietic cells. Oncogene. 2005 May 5; 24(20):3339-47.
  View in: PubMed
 
48. Yin H, Lee GI, Sedey KA, Rodriguez JM, Wang HG, Sebti SM, Hamilton AD. Terephthalamide derivatives as mimetics of helical peptides: disruption of the Bcl-x(L)/Bak interaction. J Am Chem Soc. 2005 Apr 20; 127(15):5463-8.
  View in: PubMed
 
49. Araya R, Hirai I, Meyerkord CL, Wang HG. Loss of RPA1 induces Chk2 phosphorylation through a caffeine-sensitive pathway. FEBS Lett. 2005 Jan 3; 579(1):157-61.
  View in: PubMed
 
50. Yamaguchi H, Wang HG. CHOP is involved in endoplasmic reticulum stress-induced apoptosis by enhancing DR5 expression in human carcinoma cells. J Biol Chem. 2004 Oct 29; 279(44):45495-502.
  View in: PubMed
 
51. Yamaguchi H, Chen J, Bhalla K, Wang HG. Regulation of Bax activation and apoptotic response to microtubule-damaging agents by p53 transcription-dependent and -independent pathways. J Biol Chem. 2004 Sep 17; 279(38):39431-7.
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52. Hirai I, Sasaki T, Wang HG. Human hRad1 but not hRad9 protects hHus1 from ubiquitin-proteasomal degradation. Oncogene. 2004 Jul 1; 23(30):5124-30.
  View in: PubMed
 
53. Terrones O, Antonsson B, Yamaguchi H, Wang HG, Liu J, Lee RM, Herrmann A, Basañez G. Lipidic pore formation by the concerted action of proapoptotic BAX and tBID. J Biol Chem. 2004 Jul 16; 279(29):30081-91.
  View in: PubMed
 
54. Dan HC, Sun M, Kaneko S, Feldman RI, Nicosia SV, Wang HG, Tsang BK, Cheng JQ. Akt phosphorylation and stabilization of X-linked inhibitor of apoptosis protein (XIAP). J Biol Chem. 2004 Feb 13; 279(7):5405-12.
  View in: PubMed
 
55. Terajima D, Yamada S, Uchino R, Ikawa S, Ikeda M, Shida K, Arai Y, Wang HG, Satoh N, Satake M. Identification and sequence of seventy-nine new transcripts expressed in hemocytes of Ciona intestinalis, three of which may be involved in characteristic cell-cell communication. DNA Res. 2003 Oct 31; 10(5):203-12.
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56. Fuino L, Bali P, Wittmann S, Donapaty S, Guo F, Yamaguchi H, Wang HG, Atadja P, Bhalla K. Histone deacetylase inhibitor LAQ824 down-regulates Her-2 and sensitizes human breast cancer cells to trastuzumab, taxotere, gemcitabine, and epothilone B. Mol Cancer Ther. 2003 Oct; 2(10):971-84.
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57. Lee MW, Hirai I, Wang HG. Caspase-3-mediated cleavage of Rad9 during apoptosis. Oncogene. 2003 Sep 25; 22(41):6340-6.
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58. Chen T, Yang I, Irby R, Shain KH, Wang HG, Quackenbush J, Coppola D, Cheng JQ, Yeatman TJ. Regulation of caspase expression and apoptosis by adenomatous polyposis coli. Cancer Res. 2003 Aug 1; 63(15):4368-74.
  View in: PubMed
 
59. Terajima D, Shida K, Takada N, Kasuya A, Rokhsar D, Satoh N, Satake M, Wang HG. Identification of candidate genes encoding the core components of the cell death machinery in the Ciona intestinalis genome. Cell Death Differ. 2003 Jun; 10(6):749-53.
  View in: PubMed
 
60. Yamaguchi H, Bhalla K, Wang HG. Bax plays a pivotal role in thapsigargin-induced apoptosis of human colon cancer HCT116 cells by controlling Smac/Diablo and Omi/HtrA2 release from mitochondria. Cancer Res. 2003 Apr 1; 63(7):1483-9.
  View in: PubMed
 
61. Griffin D, Wittmann S, Guo F, Nimmanapalli R, Bali P, Wang HG, Bhalla K. Molecular determinants of epothilone B derivative (BMS 247550) and Apo-2L/TRAIL-induced apoptosis of human ovarian cancer cells. Gynecol Oncol. 2003 Apr; 89(1):37-47.
  View in: PubMed
 
62. Yoshida K, Wang HG, Miki Y, Kufe D. Protein kinase Cdelta is responsible for constitutive and DNA damage-induced phosphorylation of Rad9. EMBO J. 2003 Mar 17; 22(6):1431-41.
  View in: PubMed
 
63. Nimmanapalli R, O'Bryan E, Kuhn D, Yamaguchi H, Wang HG, Bhalla KN. Regulation of 17-AAG-induced apoptosis: role of Bcl-2, Bcl-XL, and Bax downstream of 17-AAG-mediated down-regulation of Akt, Raf-1, and Src kinases. Blood. 2003 Jul 1; 102(1):269-75.
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64. Wittmann S, Bali P, Donapaty S, Nimmanapalli R, Guo F, Yamaguchi H, Huang M, Jove R, Wang HG, Bhalla K. Flavopiridol down-regulates antiapoptotic proteins and sensitizes human breast cancer cells to epothilone B-induced apoptosis. Cancer Res. 2003 Jan 1; 63(1):93-9.
  View in: PubMed
 
65. Dehal P, Satou Y, Campbell RK, Chapman J, Degnan B, De Tomaso A, Davidson B, Di Gregorio A, Gelpke M, Goodstein DM, Harafuji N, Hastings KE, Ho I, Hotta K, Huang W, Kawashima T, Lemaire P, Martinez D, Meinertzhagen IA, Necula S, Nonaka M, Putnam N, Rash S, Saiga H, Satake M, Terry A, Yamada L, Wang HG, Awazu S, Azumi K, Boore J, Branno M, Chin-Bow S, DeSantis R, Doyle S, Francino P, Keys DN, Haga S, Hayashi H, Hino K, Imai KS, Inaba K, Kano S, Kobayashi K, Kobayashi M, Lee BI, Makabe KW, Manohar C, Matassi G, Medina M, Mochizuki Y, Mount S, Morishita T, Miura S, Nakayama A, Nishizaka S, Nomoto H, Ohta F, Oishi K, Rigoutsos I, Sano M, Sasaki A, Sasakura Y, Shoguchi E, Shin-i T, Spagnuolo A, Stainier D, Suzuki MM, Tassy O, Takatori N, Tokuoka M, Yagi K, Yoshizaki F, Wada S, Zhang C, Hyatt PD, Larimer F, Detter C, Doggett N, Glavina T, Hawkins T, Richardson P, Lucas S, Kohara Y, Levine M, Satoh N, Rokhsar DS. The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins. Science. 2002 Dec 13; 298(5601):2157-67.
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66. Yamaguchi H, Wang HG. Bcl-XL protects BimEL-induced Bax conformational change and cytochrome C release independent of interacting with Bax or BimEL. J Biol Chem. 2002 Nov 1; 277(44):41604-12.
  View in: PubMed
 
67. Hirai I, Wang HG. A role of the C-terminal region of human Rad9 (hRad9) in nuclear transport of the hRad9 checkpoint complex. J Biol Chem. 2002 Jul 12; 277(28):25722-7.
  View in: PubMed
 
68. Guo F, Nimmanapalli R, Paranawithana S, Wittman S, Griffin D, Bali P, O'Bryan E, Fumero C, Wang HG, Bhalla K. Ectopic overexpression of second mitochondria-derived activator of caspases (Smac/DIABLO) or cotreatment with N-terminus of Smac/DIABLO peptide potentiates epothilone B derivative-(BMS 247550) and Apo-2L/TRAIL-induced apoptosis. Blood. 2002 May 1; 99(9):3419-26.
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69. Yoshida K, Komatsu K, Wang HG, Kufe D. c-Abl tyrosine kinase regulates the human Rad9 checkpoint protein in response to DNA damage. Mol Cell Biol. 2002 May; 22(10):3292-300.
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70. Yamaguchi H, Paranawithana SR, Lee MW, Huang Z, Bhalla KN, Wang HG. Epothilone B analogue (BMS-247550)-mediated cytotoxicity through induction of Bax conformational change in human breast cancer cells. Cancer Res. 2002 Jan 15; 62(2):466-71.
  View in: PubMed
 
71. Cunnick JM, Meng S, Ren Y, Desponts C, Wang HG, Djeu JY, Wu J. Regulation of the mitogen-activated protein kinase signaling pathway by SHP2. J Biol Chem. 2002 Mar 15; 277(11):9498-504.
  View in: PubMed
 
72. Yamaguchi H, Wang HG. The protein kinase PKB/Akt regulates cell survival and apoptosis by inhibiting Bax conformational change. Oncogene. 2001 Nov 22; 20(53):7779-86.
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73. Hirai I, Wang HG. Survival-factor-induced phosphorylation of Bad results in its dissociation from Bcl-x(L) but not Bcl-2. Biochem J. 2001 Oct 15; 359(Pt 2):345-52.
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74. Cuddeback SM, Yamaguchi H, Komatsu K, Miyashita T, Yamada M, Wu C, Singh S, Wang HG. Molecular cloning and characterization of Bif-1. A novel Src homology 3 domain-containing protein that associates with Bax. J Biol Chem. 2001 Jun 8; 276(23):20559-65.
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75. Komatsu K, Wharton W, Hang H, Wu C, Singh S, Lieberman HB, Pledger WJ, Wang HG. PCNA interacts with hHus1/hRad9 in response to DNA damage and replication inhibition. Oncogene. 2000 Nov 2; 19(46):5291-7.
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76. Komatsu K, Hopkins KM, Lieberman HB, Wang H. Schizosaccharomyces pombe Rad9 contains a BH3-like region and interacts with the anti-apoptotic protein Bcl-2. FEBS Lett. 2000 Sep 15; 481(2):122-6.
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77. Neshat MS, Raitano AB, Wang HG, Reed JC, Sawyers CL. The survival function of the Bcr-Abl oncogene is mediated by Bad-dependent and -independent pathways: roles for phosphatidylinositol 3-kinase and Raf. Mol Cell Biol. 2000 Feb; 20(4):1179-86.
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78. SchĂĽrmann A, Mooney AF, Sanders LC, Sells MA, Wang HG, Reed JC, Bokoch GM. p21-activated kinase 1 phosphorylates the death agonist bad and protects cells from apoptosis. Mol Cell Biol. 2000 Jan; 20(2):453-61.
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79. Komatsu K, Miyashita T, Hang H, Hopkins KM, Zheng W, Cuddeback S, Yamada M, Lieberman HB, Wang HG. Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis. Nat Cell Biol. 2000 Jan; 2(1):1-6.
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80. James HJ, Sharer LR, Zhang Q, Wang HG, Epstein LG, Reed JC, Gelbard HA. Expression of caspase-3 in brains from paediatric patients with HIV-1 encephalitis. Neuropathol Appl Neurobiol. 1999 Oct; 25(5):380-6.
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81. Chen W, Wang HG, Srinivasula SM, Alnemri ES, Cooper NR. B cell apoptosis triggered by antigen receptor ligation proceeds via a novel caspase-dependent pathway. J Immunol. 1999 Sep 1; 163(5):2483-91.
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82. Wang HG, Pathan N, Ethell IM, Krajewski S, Yamaguchi Y, Shibasaki F, McKeon F, Bobo T, Franke TF, Reed JC. Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD. Science. 1999 Apr 9; 284(5412):339-43.
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83. Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, Wang HG, Reed JC, Nicholson DW, Alnemri ES, Green DR, Martin SJ. Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. J Cell Biol. 1999 Jan 25; 144(2):281-92.
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84. Kitada S, Andersen J, Akar S, Zapata JM, Takayama S, Krajewski S, Wang HG, Zhang X, Bullrich F, Croce CM, Rai K, Hines J, Reed JC. Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with In vitro and In vivo chemoresponses. Blood. 1998 May 1; 91(9):3379-89.
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85. Wang HG, Reed JC. Mechanisms of Bcl-2 protein function. Histol Histopathol. 1998 Apr; 13(2):521-30.
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86. Wang HG, Reed JC. Bc1-2, Raf-1 and mitochondrial regulation of apoptosis. Biofactors. 1998; 8(1-2):13-6.
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87. Kitada S, Krajewska M, Zhang X, Scudiero D, Zapata JM, Wang HG, Shabaik A, Tudor G, Krajewski S, Myers TG, Johnson GS, Sausville EA, Reed JC. Expression and location of pro-apoptotic Bcl-2 family protein BAD in normal human tissues and tumor cell lines. Am J Pathol. 1998 Jan; 152(1):51-61.
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88. Zapata JM, Krajewska M, Krajewski S, Huang RP, Takayama S, Wang HG, Adamson E, Reed JC. Expression of multiple apoptosis-regulatory genes in human breast cancer cell lines and primary tumors. Breast Cancer Res Treat. 1998 Jan; 47(2):129-40.
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89. Chhanabhai M, Krajewski S, Krajewska M, Wang HG, Reed JC, Gascoyne RD. Immunohistochemical analysis of interleukin-1beta-converting enzyme/Ced-3 family protease, CPP32/Yama/Caspase-3, in Hodgkin's disease. Blood. 1997 Sep 15; 90(6):2451-5.
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90. Susin SA, Zamzami N, Castedo M, Daugas E, Wang HG, Geley S, Fassy F, Reed JC, Kroemer G. The central executioner of apoptosis: multiple connections between protease activation and mitochondria in Fas/APO-1/CD95- and ceramide-induced apoptosis. J Exp Med. 1997 Jul 7; 186(1):25-37.
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91. Krajewski S, Gascoyne RD, Zapata JM, Krajewska M, Kitada S, Chhanabhai M, Horsman D, Berean K, Piro LD, Fugier-Vivier I, Liu YJ, Wang HG, Reed JC. Immunolocalization of the ICE/Ced-3-family protease, CPP32 (Caspase-3), in non-Hodgkin's lymphomas, chronic lymphocytic leukemias, and reactive lymph nodes. Blood. 1997 May 15; 89(10):3817-25.
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92. Krajewska M, Wang HG, Krajewski S, Zapata JM, Shabaik A, Gascoyne R, Reed JC. Immunohistochemical analysis of in vivo patterns of expression of CPP32 (Caspase-3), a cell death protease. Cancer Res. 1997 Apr 15; 57(8):1605-13.
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93. Keane RW, Srinivasan A, Foster LM, Testa MP, Ord T, Nonner D, Wang HG, Reed JC, Bredesen DE, Kayalar C. Activation of CPP32 during apoptosis of neurons and astrocytes. J Neurosci Res. 1997 Apr 15; 48(2):168-80.
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94. Perry DK, Smyth MJ, Wang HG, Reed JC, Duriez P, Poirier GG, Obeid LM, Hannun YA. Bcl-2 acts upstream of the PARP protease and prevents its activation. Cell Death Differ. 1997 Jan; 4(1):29-33.
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95. Wang HG, Rapp UR, Reed JC. Bcl-2 targets the protein kinase Raf-1 to mitochondria. Cell. 1996 Nov 15; 87(4):629-38.
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96. Wang HG, Takayama S, Rapp UR, Reed JC. Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1. Proc Natl Acad Sci U S A. 1996 Jul 9; 93(14):7063-8.
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97. Zhang Z, Vuori K, Wang H, Reed JC, Ruoslahti E. Integrin activation by R-ras. Cell. 1996 Apr 5; 85(1):61-9.
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98. Liu Y, Lee MO, Wang HG, Li Y, Hashimoto Y, Klaus M, Reed JC, Zhang X. Retinoic acid receptor beta mediates the growth-inhibitory effect of retinoic acid by promoting apoptosis in human breast cancer cells. Mol Cell Biol. 1996 Mar; 16(3):1138-49.
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99. Lin EY, Orlofsky A, Wang HG, Reed JC, Prystowsky MB. A1, a Bcl-2 family member, prolongs cell survival and permits myeloid differentiation. Blood. 1996 Feb 1; 87(3):983-92.
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100. Yagihashi S, Yamagishi S, Wada R, Sugimoto K, Baba M, Wong HG, Fujimoto J, Nishimura C, Kokai Y. Galactosemic neuropathy in transgenic mice for human aldose reductase. Diabetes. 1996 Jan; 45(1):56-9.
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101. Reed JC, Miyashita T, Krajewski S, Takayama S, Aime-Sempe C, Kitada S, Sato T, Wang HG, Harigai M, Hanada M, Krajewska M, Kochel K, Millan J, Kobayashi H. Bcl-2 family proteins and the regulation of programmed cell death in leukemia and lymphoma. Cancer Treat Res. 1996; 84:31-72.
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102. Reed JC, Miyashita T, Takayama S, Wang HG, Sato T, Krajewski S, Aimé-Sempé C, Bodrug S, Kitada S, Hanada M. BCL-2 family proteins: regulators of cell death involved in the pathogenesis of cancer and resistance to therapy. J Cell Biochem. 1996 Jan; 60(1):23-32.
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103. Reed JC, Zha H, Aime-Sempe C, Takayama S, Wang HG. Structure-function analysis of Bcl-2 family proteins. Regulators of programmed cell death. Adv Exp Med Biol. 1996; 406:99-112.
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104. Martin SJ, Newmeyer DD, Mathias S, Farschon DM, Wang HG, Reed JC, Kolesnick RN, Green DR. Cell-free reconstitution of Fas-, UV radiation- and ceramide-induced apoptosis. EMBO J. 1995 Nov 1; 14(21):5191-200.
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105. Wang HG, Millan JA, Cox AD, Der CJ, Rapp UR, Beck T, Zha H, Reed JC. R-Ras promotes apoptosis caused by growth factor deprivation via a Bcl-2 suppressible mechanism. J Cell Biol. 1995 May; 129(4):1103-14.
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106. Krajewski S, Krajewska M, Shabaik A, Miyashita T, Wang HG, Reed JC. Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2. Am J Pathol. 1994 Dec; 145(6):1323-36.
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107. Krajewski S, Krajewska M, Shabaik A, Wang HG, Irie S, Fong L, Reed JC. Immunohistochemical analysis of in vivo patterns of Bcl-X expression. Cancer Res. 1994 Nov 1; 54(21):5501-7.
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108. Sato T, Hanada M, Bodrug S, Irie S, Iwama N, Boise LH, Thompson CB, Golemis E, Fong L, Wang HG, et al. Interactions among members of the Bcl-2 protein family analyzed with a yeast two-hybrid system. Proc Natl Acad Sci U S A. 1994 Sep 27; 91(20):9238-42.
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109. Wang HG, Miyashita T, Takayama S, Sato T, Torigoe T, Krajewski S, Tanaka S, Hovey L, Troppmair J, Rapp UR, et al. Apoptosis regulation by interaction of Bcl-2 protein and Raf-1 kinase. Oncogene. 1994 Sep; 9(9):2751-6.
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110. Selvakumaran M, Lin HK, Miyashita T, Wang HG, Krajewski S, Reed JC, Hoffman B, Liebermann D. Immediate early up-regulation of bax expression by p53 but not TGF beta 1: a paradigm for distinct apoptotic pathways. Oncogene. 1994 Jun; 9(6):1791-8.
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111. Miyashita T, Krajewski S, Krajewska M, Wang HG, Lin HK, Liebermann DA, Hoffman B, Reed JC. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene. 1994 Jun; 9(6):1799-805.
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Amin, Shantu
Kester, Mark
Loughran, Thomas
Sung, Shen-shu
Takahashi, Yoshinori
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