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    Keigo Machida, PhD

    TitleAssociate Professor of Molecular Microbiology & Immunology
    SchoolKeck School of Medicine of USC
    DepartmentMolecular Microbiology and Immunology
    AddressHMR 503C 2011 Zonal Avenue
    Health Sciences Campus
    Los Angeles California 90089
    Phone+1 323 442 2692
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      Collapse Overview 
      Collapse Overview
      Hepatitis C Virus (HCV) is a “silent stalker” in infected people, who can develop hepatocellular carcinomas (HCC) decades later. Our short-term goal is to study three areas:

      (i) Host-pathogen interactions to identify the mechanism of HCV-associated HCC

      (ii) Molecular virology of lymphotropic HCV in viral persistence and pathogenesis

      (iii) Cancer biology in liver oncogenesis generated from tumor-initiating cells (TICs: “bad seeds” of treatment-resistant HCC) induced by interactions between environmental factors (alcohol, obesity) and HCV.

      Our lab’s long-term goal is to test new therapeutic modalities for HCC in HCV-infected patients with alcoholism and/or obesity.

      Our experience and resources on TICs have provided a unique opportunity to functionally dissect the alcohol-mediated self-renewal of liver TICs via TLR4 signaling. The p53 tumor suppressor acts as a barrier against stem cell proliferation, and inactivation of p53, or its stabilizing partner NUMB (cell fate decision molecule), leads to expansion of TICs. Although treatment efficacy of HCV has been dramatically improved in recent years, the incidence of HCV-associated HCC keeps rising due to the prevalence of obesity, alcoholism and illicit drug usage in HCV patients. Thus, we will continue our research on the development of new therapeutic modalities for HCC.

      Collapse Biography 
      Collapse Education and Training
      University of Tokyo, School of Medicine, Tokyo, JapanPh.D.03/2001Molecular Immunology
      University of Southern California, Los Angeles, CAPost-doc05/2003Molecular Virology
      Howard Hughes Medical Institute, Los Angeles, CAPost-doc08/2005Cancer Biology
      Collapse Awards and Honors
      Japan Society for the Promotion of Science1998  - 2001Scholarship
      Asian Pacific Association for the Study of the Liver (APASL)2007Young Investigator Award
      Research Center for Liver Diseases 2007  - 2007USC Research Center for Liver Diseases Pilot Funding Award
      Liver Meeting of AASLD2008Presidential Poster of Distinction
      American Cancer Society (ACS) 2011  - 2016Research Scholar

      Collapse Research 
      Collapse Research Activities and Funding
      Southern California Research Center for ALPD and Cirrhosis
      NIH/NIAAA P50 AA11999Jan 1, 2015 - Dec 31, 2019
      Role: Co-director of Animal Core Facility and Project 3 leader
      Role Description: This center grant supports our central research theme: elucidation of mechanisms by which alcohol sensitizes and primes the liver and pancreas for injury. Animal Core provides the intragastric ethanol infusion model to the Center members.

      Collapse ORNG Applications 
      Collapse Featured Publications
      Collapse Websites
      Collapse Featured Presentations

      Collapse Bibliographic 
      Collapse Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
      List All   |   Timeline
      1. Baulies A, Montero J, Matías N, Insausti N, Terrones O, Basañez G, Vallejo C, de La Rosa LC, Martinez L, Robles D, Morales A, Abian J, Carrascal M, Machida K, Kumar DBU, Tsukamoto H, Kaplowitz N, Garcia-Ruiz C, Fernández-Checa JC. The 2-oxoglutarate carrier promotes liver cancer by sustaining mitochondrial GSH despite cholesterol loading. Redox Biol. 2017 Sep 14; 14:164-177. PMID: 28942194.
        View in: PubMed
      2. Debebe A, Medina V, Chen CY, Mahajan IM, Jia C, Fu D, He L, Zeng N, Stiles BW, Chen CL, Wang M, Aggarwal KR, Peng Z, Huang J, Chen J, Li M, Dong T, Atkins S, Borok Z, Yuan W, Machida K, Ju C, Kahn M, Johnson D, Stiles BL. Wnt/ß-catenin activation and macrophage induction during liver cancer development following steatosis. Oncogene. 2017 Jul 03. PMID: 28671671.
        View in: PubMed
      3. Chen CL, Huang JY, Wang CH, Tahara SM, Zhou L, Kondo Y, Schechter J, Su L, Lai MM, Wakita T, Cosset FL, Jung JU, Machida K. Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7.2. Nat Commun. 2017 Jan 09; 8:13882. PMID: 28067225.
        View in: PubMed
      4. Chen J, Shukla V, Farci P, Andricovich J, Jogunoori W, Kwong LN, Katz LH, Shetty K, Rashid A, Su X, White J, Li L, Wang AY, Blechacz B, Raju GS, Davila M, Nguyen BN, Stroehlein JR, Chen J, Kim SS, Levin H, Machida K, Tsukamoto H, Michaely P, Tzatsos A, Mishra B, Amdur R, Mishra L. Loss of the transforming growth factor-ß effector ß2-Spectrin promotes genomic instability. Hepatology. 2017 Feb; 65(2):678-693. PMID: 28114741.
        View in: PubMed
      5. Machida K. Existence of cancer stem cells in hepatocellular carcinoma: myth or reality? Hepatol Int. 2017 Mar; 11(2):143-147. PMID: 27990610.
        View in: PubMed
      6. Chen J, Yao ZX, Chen JS, Gi YJ, Muñoz NM, Kundra S, Herlong HF, Jeong YS, Goltsov A, Ohshiro K, Mistry NA, Zhang J, Su X, Choufani S, Mitra A, Li S, Mishra B, White J, Rashid A, Wang AY, Javle M, Davila M, Michaely P, Weksberg R, Hofstetter WL, Finegold MJ, Shay JW, Machida K, Tsukamoto H, Mishra L. TGF-ß/ß2-spectrin/CTCF-regulated tumor suppression in human stem cell disorder Beckwith-Wiedemann syndrome. J Clin Invest. 2016 Feb; 126(2):527-42. PMID: 26784546; PMCID: PMC4731168.
      7. Chen CL, Uthaya Kumar DB, Punj V, Xu J, Sher L, Tahara SM, Hess S, Machida K. NANOG Metabolically Reprograms Tumor-Initiating Stem-like Cells through Tumorigenic Changes in Oxidative Phosphorylation and Fatty Acid Metabolism. Cell Metab. 2016 Jan 12; 23(1):206-19. PMID: 26724859; PMCID: PMC4715587 [Available on 01/12/17].
      8. Uthaya Kumar DB, Chen CL, Liu JC, Feldman DE, Sher LS, French S, DiNorcia J, French SW, Naini BV, Junrungsee S, Agopian VG, Zarrinpar A, Machida K. TLR4 Signaling via NANOG Cooperates With STAT3 to Activate Twist1 and Promote Formation of Tumor-Initiating Stem-Like Cells in Livers of Mice. Gastroenterology. 2016 Mar; 150(3):707-19. PMID: 26582088; PMCID: PMC4766021 [Available on 03/01/17].
      9. Siddique HR, Feldman DE, Chen CL, Punj V, Tokumitsu H, Machida K. NUMB phosphorylation destabilizes p53 and promotes self-renewal of tumor-initiating cells by a NANOG-dependent mechanism in liver cancer. Hepatology. 2015 Nov; 62(5):1466-79. PMID: 26174965; PMCID: PMC4618247 [Available on 11/01/16].
      10. He S, Zhao Z, Yang Y, O'Connell D, Zhang X, Oh S, Ma B, Lee JH, Zhang T, Varghese B, Yip J, Dolatshahi Pirooz S, Li M, Zhang Y, Li GM, Ellen Martin S, Machida K, Liang C. Truncating mutation in the autophagy gene UVRAG confers oncogenic properties and chemosensitivity in colorectal cancers. Nat Commun. 2015 Aug 03; 6:7839. PMID: 26234763; PMCID: PMC4526116.
      11. Feng T, Dzieran J, Gu X, Marhenke S, Vogel A, Machida K, Weiss TS, Ruemmele P, Kollmar O, Hoffmann P, Grässer F, Allgayer H, Fabian J, Weng HL, Teufel A, Maass T, Meyer C, Lehmann U, Zhu C, Mertens PR, Gao CF, Dooley S, Meindl-Beinker NM. Smad7 regulates compensatory hepatocyte proliferation in damaged mouse liver and positively relates to better clinical outcome in human hepatocellular carcinoma. Clin Sci (Lond). 2015 Jun; 128(11):761-74. PMID: 25602745.
        View in: PubMed
      12. Machida K, Feldman DE, Tsukamoto H. TLR4-dependent tumor-initiating stem cell-like cells (TICs) in alcohol-associated hepatocellular carcinogenesis. Adv Exp Med Biol. 2015; 815:131-44. PMID: 25427905.
        View in: PubMed
      13. Lazaro R, Wu R, Lee S, Zhu NL, Chen CL, French SW, Xu J, Machida K, Tsukamoto H. Osteopontin deficiency does not prevent but promotes alcoholic neutrophilic hepatitis in mice. Hepatology. 2015 Jan; 61(1):129-40. PMID: 25132354; PMCID: PMC4280361.
      14. Sriram G, Jankowski W, Kasikara C, Reichman C, Saleh T, Nguyen KQ, Li J, Hornbeck P, Machida K, Liu T, Li H, Kalodimos CG, Birge RB. Iterative tyrosine phosphorylation controls non-canonical domain utilization in Crk. Oncogene. 2015 Aug 06; 34(32):4260-9. PMID: 25381819; PMCID: PMC4706174.
      15. Takemoto K, Hatano E, Iwaisako K, Takeiri M, Noma N, Ohmae S, Toriguchi K, Tanabe K, Tanaka H, Seo S, Taura K, Machida K, Takeda N, Saji S, Uemoto S, Asagiri M. Necrostatin-1 protects against reactive oxygen species (ROS)-induced hepatotoxicity in acetaminophen-induced acute liver failure. FEBS Open Bio. 2014; 4:777-87. PMID: 25349782; PMCID: PMC4208088.
      16. Ng KY, Yin T, Machida K, Wu YI, Mayer BJ. Phosphorylation of Dok1 by Abl family kinases inhibits CrkI transforming activity. Oncogene. 2015 May 14; 34(20):2650-9. PMID: 25043303; PMCID: PMC4302068.
      17. Chen CL, Tsukamoto H, Machida K. Oncogenic signaling pathways and origins of tumor-initiating stem-like cells of hepatocellular carcinomas induced by hepatitis C virus, alcohol and/or obesity. Hepatol Int. 2014 Jul; 8(3):330-8. PMID: 26202636.
        View in: PubMed
      18. Kondo Y, Ninomiya M, Kimura O, Machida K, Funayama R, Nagashima T, Kobayashi K, Kakazu E, Kato T, Nakayama K, Lai MM, Shimosegawa T. HCV infection enhances Th17 commitment, which could affect the pathogenesis of autoimmune diseases. PLoS One. 2014; 9(6):e98521. PMID: 24905921; PMCID: PMC4048196.
      19. Tsukamoto H, Mishra L, Machida K. Alcohol, TLR4-TGF-ß antagonism, and liver cancer. Hepatol Int. 2014 Sep; 8 Suppl 2:408-12. PMID: 26201318; PMCID: PMC4900455.
      20. Chen CL, Tsukamoto H, Liu JC, Kashiwabara C, Feldman D, Sher L, Dooley S, French SW, Mishra L, Petrovic L, Jeong JH, Machida K. Reciprocal regulation by TLR4 and TGF-ß in tumor-initiating stem-like cells. J Clin Invest. 2013 Jul; 123(7):2832-49. PMID: 23921128; PMCID: PMC3696549.
      21. Machida K. Tumor-initiating stem-like cells and drug resistance: carcinogenesis through Toll-like receptors, environmental factors, and virus. Drug Deliv Transl Res. 2013 Apr; 3(2):152-64. PMID: 25787983.
        View in: PubMed
      22. Feldman DE, Chen C, Punj V, Machida K. The TBC1D15 oncoprotein controls stem cell self-renewal through destabilization of the Numb-p53 complex. PLoS One. 2013; 8(2):e57312. PMID: 23468968; PMCID: PMC3584131.
      23. Kondo Y, Uno K, Machida K, Terajima M. PPARs and Liver Disease. PPAR Res. 2013; 2013:896412. PMID: 23476632; PMCID: PMC3576795.
      24. Hong B, Lee SH, Song XT, Jones L, Machida K, Huang XF, Chen SY. A super TLR agonist to improve efficacy of dendritic cell vaccine in induction of anti-HCV immunity. PLoS One. 2012; 7(11):e48614. PMID: 23144910; PMCID: PMC3492467.
      25. Liu Z, Tian Y, Machida K, Lai MM, Luo G, Foung SK, Ou JH. Transient activation of the PI3K-AKT pathway by hepatitis C virus to enhance viral entry. J Biol Chem. 2012 Dec 07; 287(50):41922-30. PMID: 23095753; PMCID: PMC3516739.
      26. Liu HM, Aizaki H, Machida K, Ou JH, Lai MM. Hepatitis C virus translation preferentially depends on active RNA replication. PLoS One. 2012; 7(8):e43600. PMID: 22937067; PMCID: PMC3427374.
      27. von Montfort C, Matias N, Fernandez A, Fucho R, Conde de la Rosa L, Martinez-Chantar ML, Mato JM, Machida K, Tsukamoto H, Murphy MP, Mansouri A, Kaplowitz N, Garcia-Ruiz C, Fernandez-Checa JC. Mitochondrial GSH determines the toxic or therapeutic potential of superoxide scavenging in steatohepatitis. J Hepatol. 2012 Oct; 57(4):852-9. PMID: 22687340; PMCID: PMC3445734.
      28. Sir D, Kuo CF, Tian Y, Liu HM, Huang EJ, Jung JU, Machida K, Ou JH. Replication of hepatitis C virus RNA on autophagosomal membranes. J Biol Chem. 2012 May 25; 287(22):18036-43. PMID: 22496373; PMCID: PMC3365724.
      29. Ueno A, Lazaro R, Wang PY, Higashiyama R, Machida K, Tsukamoto H. Mouse intragastric infusion (iG) model. Nat Protoc. 2012 Mar 29; 7(4):771-81. PMID: 22461066; PMCID: PMC4197794.
      30. Machida K, Chen CL, Liu JC, Kashiwabara C, Feldman D, French SW, Sher L, Hyeongnam JJ, Tsukamoto H. Cancer stem cells generated by alcohol, diabetes, and hepatitis C virus. J Gastroenterol Hepatol. 2012 Mar; 27 Suppl 2:19-22. PMID: 22320911; PMCID: PMC3306127.
      31. Tsukamoto H, Zhu NL, Wang J, Asahina K, Machida K. Morphogens and hepatic stellate cell fate regulation in chronic liver disease. J Gastroenterol Hepatol. 2012 Mar; 27 Suppl 2:94-8. PMID: 22320925; PMCID: PMC3337168.
      32. Feldman DE, Chen C, Punj V, Tsukamoto H, Machida K. Pluripotency factor-mediated expression of the leptin receptor (OB-R) links obesity to oncogenesis through tumor-initiating stem cells. Proc Natl Acad Sci U S A. 2012 Jan 17; 109(3):829-34. PMID: 22207628; PMCID: PMC3271911.
      33. Inn KS, Lee SH, Rathbun JY, Wong LY, Toth Z, Machida K, Ou JH, Jung JU. Inhibition of RIG-I-mediated signaling by Kaposi's sarcoma-associated herpesvirus-encoded deubiquitinase ORF64. J Virol. 2011 Oct; 85(20):10899-904. PMID: 21835791; PMCID: PMC3187500.
      34. Tsukiyama-Kohara K, Sekiguchi S, Kasama Y, Salem NE, Machida K, Kohara M. Hepatitis C virus-related lymphomagenesis in a mouse model. ISRN Hematol. 2011; 2011:167501. PMID: 22084693; PMCID: PMC3195281.
      35. Sriram G, Reichman C, Tunceroglu A, Kaushal N, Saleh T, Machida K, Mayer B, Ge Q, Li J, Hornbeck P, Kalodimos CG, Birge RB. Phosphorylation of Crk on tyrosine 251 in the RT loop of the SH3C domain promotes Abl kinase transactivation. Oncogene. 2011 Nov 17; 30(46):4645-55. PMID: 21602891; PMCID: PMC3311107.
      36. Szabo G, Billiar TR, Machida K, Crispe IN, Seki E. Toll-like receptor signaling in liver diseases. Gastroenterol Res Pract. 2010; 2010:971270. PMID: 21789039; PMCID: PMC3123973.
      37. Machida K. TLRs, Alcohol, HCV, and Tumorigenesis. Gastroenterol Res Pract. 2010; 2010:518674. PMID: 21331379; PMCID: PMC3038599.
      38. Zhong S, Machida K, Tsukamoto H, Johnson DL. Alcohol induces RNA polymerase III-dependent transcription through c-Jun by co-regulating TATA-binding protein (TBP) and Brf1 expression. J Biol Chem. 2011 Jan 28; 286(4):2393-401. PMID: 21106530; PMCID: PMC3024733.
      39. Machida K, McNamara G, Cheng KT, Huang J, Wang CH, Comai L, Ou JH, Lai MM. Hepatitis C virus inhibits DNA damage repair through reactive oxygen and nitrogen species and by interfering with the ATM-NBS1/Mre11/Rad50 DNA repair pathway in monocytes and hepatocytes. J Immunol. 2010 Dec 01; 185(11):6985-98. PMID: 20974981; PMCID: PMC3101474.
      40. Yeligar SM, Machida K, Kalra VK. Ethanol-induced HO-1 and NQO1 are differentially regulated by HIF-1alpha and Nrf2 to attenuate inflammatory cytokine expression. J Biol Chem. 2010 Nov 12; 285(46):35359-73. PMID: 20833713; PMCID: PMC2975160.
      41. Lai CK, Jeng KS, Machida K, Lai MM. Hepatitis C virus egress and release depend on endosomal trafficking of core protein. J Virol. 2010 Nov; 84(21):11590-8. PMID: 20739534; PMCID: PMC2953145.
      42. Zheng J, Machida K, Antoku S, Ng KY, Claffey KP, Mayer BJ. Proteins that bind the Src homology 3 domain of CrkI have distinct roles in Crk transformation. Oncogene. 2010 Dec 02; 29(48):6378-89. PMID: 20729917; PMCID: PMC2996469.
      43. Kondo Y, Ueno Y, Kakazu E, Kobayashi K, Shiina M, Tamai K, Machida K, Inoue J, Wakui Y, Fukushima K, Obara N, Kimura O, Shimosegawa T. Lymphotropic HCV strain can infect human primary naïve CD4+ cells and affect their proliferation and IFN-? secretion activity. J Gastroenterol. 2011 Feb; 46(2):232-41. PMID: 20714907; PMCID: PMC4197795.
      44. Machida K, Tsukamoto H, Liu JC, Han YP, Govindarajan S, Lai MM, Akira S, Ou JH. c-Jun mediates hepatitis C virus hepatocarcinogenesis through signal transducer and activator of transcription 3 and nitric oxide-dependent impairment of oxidative DNA repair. Hepatology. 2010 Aug; 52(2):480-92. PMID: 20683948; PMCID: PMC3107125.
      45. Chen YC, Su WC, Huang JY, Chao TC, Jeng KS, Machida K, Lai MM. Polo-like kinase 1 is involved in hepatitis C virus replication by hyperphosphorylating NS5A. J Virol. 2010 Aug; 84(16):7983-93. PMID: 20534861; PMCID: PMC2916529.
      46. Szabo G, Wands JR, Eken A, Osna NA, Weinman SA, Machida K, Joe Wang H. Alcohol and hepatitis C virus--interactions in immune dysfunctions and liver damage. Alcohol Clin Exp Res. 2010 Oct; 34(10):1675-86. PMID: 20608905; PMCID: PMC3253556.
      47. Yeligar SM, Machida K, Tsukamoto H, Kalra VK. Ethanol augments RANTES/CCL5 expression in rat liver sinusoidal endothelial cells and human endothelial cells via activation of NF-kappa B, HIF-1 alpha, and AP-1. J Immunol. 2009 Nov 01; 183(9):5964-76. PMID: 19828633; PMCID: PMC3633447.
      48. Machida K, Liu JC, McNamara G, Levine A, Duan L, Lai MM. Hepatitis C virus causes uncoupling of mitotic checkpoint and chromosomal polyploidy through the Rb pathway. J Virol. 2009 Dec; 83(23):12590-600. PMID: 19793824; PMCID: PMC2786750.
      49. Tsukamoto H, Machida K, Dynnyk A, Mkrtchyan H. "Second hit" models of alcoholic liver disease. Semin Liver Dis. 2009 May; 29(2):178-87. PMID: 19387917; PMCID: PMC4197797.
      50. Machida K, Tsukiyama-Kohara K, Sekiguch S, Seike E, Tóne S, Hayashi Y, Tobita Y, Kasama Y, Shimizu M, Takahashi H, Taya C, Yonekawa H, Tanaka N, Kohara M. Hepatitis C virus and disrupted interferon signaling promote lymphoproliferation via type II CD95 and interleukins. Gastroenterology. 2009 Jul; 137(1):285-96, 296.e1-11. PMID: 19362089; PMCID: PMC4197798.
      51. Kondo Y, Machida K, Liu HM, Ueno Y, Kobayashi K, Wakita T, Shimosegawa T, Lai MM. Hepatitis C virus infection of T cells inhibits proliferation and enhances fas-mediated apoptosis by down-regulating the expression of CD44 splicing variant 6. J Infect Dis. 2009 Mar 01; 199(5):726-36. PMID: 19199548; PMCID: PMC4174598.
      52. Liu HM, Aizaki H, Choi KS, Machida K, Ou JJ, Lai MM. SYNCRIP (synaptotagmin-binding, cytoplasmic RNA-interacting protein) is a host factor involved in hepatitis C virus RNA replication. Virology. 2009 Apr 10; 386(2):249-56. PMID: 19232660; PMCID: PMC3099193.
      53. Machida K, Tsukamoto H, Mkrtchyan H, Duan L, Dynnyk A, Liu HM, Asahina K, Govindarajan S, Ray R, Ou JH, Seki E, Deshaies R, Miyake K, Lai MM. Toll-like receptor 4 mediates synergism between alcohol and HCV in hepatic oncogenesis involving stem cell marker Nanog. Proc Natl Acad Sci U S A. 2009 Feb 03; 106(5):1548-53. PMID: 19171902; PMCID: PMC2635765.
      54. Lai CK, Jeng KS, Machida K, Lai MM. Association of hepatitis C virus replication complexes with microtubules and actin filaments is dependent on the interaction of NS3 and NS5A. J Virol. 2008 Sep; 82(17):8838-48. PMID: 18562541; PMCID: PMC2519648.
      55. Machida K, Kondo Y, Huang JY, Chen YC, Cheng KT, Keck Z, Foung S, Dubuisson J, Sung VM, Lai MM. Hepatitis C virus (HCV)-induced immunoglobulin hypermutation reduces the affinity and neutralizing activities of antibodies against HCV envelope protein. J Virol. 2008 Jul; 82(13):6711-20. PMID: 18417597; PMCID: PMC2447061.
      56. Baba T, Yokoya T, Tsuda S, Kiss T, Shimojima T, Ishizaka K, Takeya H, Hirata K, Watanabe T, Nohara M, Takagi H, Nakai N, Machida K, Togashi T, Watanabe S, Wang XY, Chen CT, Shin S. Bulk electronic structure of the antiferromagnetic superconducting phase in ErNi2B2C. Phys Rev Lett. 2008 Jan 11; 100(1):017003. PMID: 18232808.
        View in: PubMed
      57. Keck ZY, Machida K, Lai MM, Ball JK, Patel AH, Foung SK. Therapeutic control of hepatitis C virus: the role of neutralizing monoclonal antibodies. Curr Top Microbiol Immunol. 2008; 317:1-38. PMID: 17990788.
        View in: PubMed
      58. Lai CK, Jeng KS, Machida K, Cheng YS, Lai MM. Hepatitis C virus NS3/4A protein interacts with ATM, impairs DNA repair and enhances sensitivity to ionizing radiation. Virology. 2008 Jan 20; 370(2):295-309. PMID: 17931678.
        View in: PubMed
      59. Kondo Y, Sung VM, Machida K, Liu M, Lai MM. Hepatitis C virus infects T cells and affects interferon-gamma signaling in T cell lines. Virology. 2007 Apr 25; 361(1):161-73. PMID: 17175001.
        View in: PubMed
      60. Kawamura H, Govindarajan S, Aswad F, Machida K, Lai MM, Sung VM, Dennert G. HCV core expression in hepatocytes protects against autoimmune liver injury and promotes liver regeneration in mice. Hepatology. 2006 Oct; 44(4):936-44. PMID: 17006910.
        View in: PubMed
      61. Machida K, Cheng KT, Lai CK, Jeng KS, Sung VM, Lai MM. Hepatitis C virus triggers mitochondrial permeability transition with production of reactive oxygen species, leading to DNA damage and STAT3 activation. J Virol. 2006 Jul; 80(14):7199-207. PMID: 16809325; PMCID: PMC1489016.
      62. Machida K, Cheng KT, Sung VM, Levine AM, Foung S, Lai MM. Hepatitis C virus induces toll-like receptor 4 expression, leading to enhanced production of beta interferon and interleukin-6. J Virol. 2006 Jan; 80(2):866-74. PMID: 16378988; PMCID: PMC1346849.
      63. Machida K, Cheng KT, Pavio N, Sung VM, Lai MM. Hepatitis C virus E2-CD81 interaction induces hypermutation of the immunoglobulin gene in B cells. J Virol. 2005 Jul; 79(13):8079-89. PMID: 15956553; PMCID: PMC1143751.
      64. Machida K, Cheng KT, Sung VM, Lee KJ, Levine AM, Lai MM. Hepatitis C virus infection activates the immunologic (type II) isoform of nitric oxide synthase and thereby enhances DNA damage and mutations of cellular genes. J Virol. 2004 Aug; 78(16):8835-43. PMID: 15280491; PMCID: PMC479064.
      65. Machida K, Cheng KT, Sung VM, Shimodaira S, Lindsay KL, Levine AM, Lai MY, Lai MM. Hepatitis C virus induces a mutator phenotype: enhanced mutations of immunoglobulin and protooncogenes. Proc Natl Acad Sci U S A. 2004 Mar 23; 101(12):4262-7. PMID: 14999097; PMCID: PMC384729.
      66. Kakuda R, Iijima T, Yaoita Y, Machida K, Kikuchi M. Secoiridoid glycosides from Gentiana scabra. J Nat Prod. 2001 Dec; 64(12):1574-5. PMID: 11754617.
        View in: PubMed
      67. Tashima Y, Kohda Y, Nonoguchi H, Ikebe M, Machida K, Star RA, Tomita K. Intranephron localization and regulation of the V1a vasopressin receptor during chronic metabolic acidosis and dehydration in rats. Pflugers Arch. 2001 Aug; 442(5):652-61. PMID: 11512020.
        View in: PubMed
      68. Sohara Y, Ishiguro N, Machida K, Kurata H, Thant AA, Senga T, Matsuda S, Kimata K, Iwata H, Hamaguchi M. Hyaluronan activates cell motility of v-Src-transformed cells via Ras-mitogen-activated protein kinase and phosphoinositide 3-kinase-Akt in a tumor-specific manner. Mol Biol Cell. 2001 Jun; 12(6):1859-68. PMID: 11408591; PMCID: PMC37347.
      69. Machida K, Ando M, Yaoita Y, Kakuda R, Kikuchi M. Studies on the constituents of Catalpa species. VI. Monoterpene glycosides from the fallen leaves of Catalpa ovata G. Don. Chem Pharm Bull (Tokyo). 2001 Jun; 49(6):732-6. PMID: 11411526.
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      70. Yaoita Y, Matsuki K, Iijima T, Nakano S, Kakuda R, Machida K, Kikuchi M. New sterols and triterpenoids from four edible mushrooms. Chem Pharm Bull (Tokyo). 2001 May; 49(5):589-94. PMID: 11383612.
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      71. Machida K, Tsukiyama-Kohara K, Seike E, Toné S, Shibasaki F, Shimizu M, Takahashi H, Hayashi Y, Funata N, Taya C, Yonekawa H, Kohara M. Inhibition of cytochrome c release in Fas-mediated signaling pathway in transgenic mice induced to express hepatitis C viral proteins. J Biol Chem. 2001 Apr 13; 276(15):12140-6. PMID: 11278624.
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      72. Kakuda R, Imai M, Yaoita Y, Machida K, Kikuchi M. Secoiridoid glycosides from the flower buds of Lonicera japonica. Phytochemistry. 2000 Dec; 55(8):879-81. PMID: 11140518.
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      73. Yaoita Y, Ishizuka T, Kakuda R, Machida K, Kikuchi M. Structures of new ceramides from the fruit bodies of Grifola frondosa. Chem Pharm Bull (Tokyo). 2000 Sep; 48(9):1356-8. PMID: 10993238.
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      74. Okai Y, Higashi-Okai K, Machida K, Nakamura H, Nakayama K, Fijita K, Tanaka T, Taniguchi M. Protective effects of alpha-tocopherol and beta-carotene on para-nonylphenol-induced inhibition of cell growth, cellular respiration and glucose-induced proton extrusion of bacteria. FEMS Microbiol Lett. 2000 Jun 15; 187(2):161-5. PMID: 10856651.
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      75. Machida K, Oyama K, Ishii M, Kakuda R, Yaoita Y, Kikuchi M. Studies of the constituents of Gardenia species. II. Terpenoids from Gardeniae Fructus. Chem Pharm Bull (Tokyo). 2000 May; 48(5):746-8. PMID: 10823717.
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      76. Okai Y, Higashi-Okai K, Machida K, Nakamura H, Nakayama K, Fujita K, Tanaka T, Otani S, Taniguchi M. Protective effect of antioxidants against para-nonylphenol-induced inhibition of cell growth in Saccharomyces cerevisiae. FEMS Microbiol Lett. 2000 Apr 01; 185(1):65-70. PMID: 10731608.
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      77. Machida K, Matsuda S, Yamaki K, Senga T, Thant AA, Kurata H, Miyazaki K, Hayashi K, Okuda T, Kitamura T, Hayakawa T, Hamaguchi M. v-Src suppresses SHPS-1 expression via the Ras-MAP kinase pathway to promote the oncogenic growth of cells. Oncogene. 2000 Mar 23; 19(13):1710-8. PMID: 10763828.
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      78. Tanaka T, Nakayama K, Machida K, Taniguchi M. Long-chain alkyl ester of AMP acts as an antagonist of glucose-induced signal transduction that mediates activation of plasma membrane proton pump in Saccharomyces cerevisiae. Microbiology. 2000 Feb; 146 ( Pt 2):377-84. PMID: 10708376.
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      79. Senga T, Miyazaki K, Machida K, Iwata H, Matsuda S, Nakashima I, Hamaguchi M. Clustered cysteine residues in the kinase domain of v-Src: critical role for protein stability, cell transformation and sensitivity to herbimycin A. Oncogene. 2000 Jan 13; 19(2):273-9. PMID: 10645006.
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      80. Machida K, Tanaka T. Farnesol-induced generation of reactive oxygen species dependent on mitochondrial transmembrane potential hyperpolarization mediated by F(0)F(1)-ATPase in yeast. FEBS Lett. 1999 Nov 26; 462(1-2):108-12. PMID: 10580101.
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      81. Thant AA, Sein TT, Liu E, Machida K, Kikkawa F, Koike T, Seiki M, Matsuda S, Hamaguchi M. Ras pathway is required for the activation of MMP-2 secretion and for the invasion of src-transformed 3Y1. Oncogene. 1999 Nov 11; 18(47):6555-63. PMID: 10597259.
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      82. Tamura A, Hebisawa A, Hayashi K, Sagara Y, Kawabe Y, Nagayama N, Machida K, Fukushima K, Yotsumoto H, Mori M. Lung cancer in patients who had received thoracoplasty for pulmonary tuberculosis. Jpn J Clin Oncol. 1999 Nov; 29(11):541-5. PMID: 10678556.
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      83. Takimoto H, Machida K, Ueki M, Tanaka T, Taniguchi M. UK-2A, B, C and D, novel antifungal antibiotics from Streptomyces sp. 517-02. IV. Comparative studies of UK-2A with antimycin A3 on cytotoxic activity and reactive oxygen species generation in LLC-PK1 cells. J Antibiot (Tokyo). 1999 May; 52(5):480-4. PMID: 10480572.
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      84. Machida K, Tanaka T, Fujita K, Taniguchi M. Farnesol-induced generation of reactive oxygen species via indirect inhibition of the mitochondrial electron transport chain in the yeast Saccharomyces cerevisiae. J Bacteriol. 1998 Sep; 180(17):4460-5. PMID: 9721283; PMCID: PMC107455.
      85. Kumar PK, Machida K, Urvil PT, Kakiuchi N, Vishnuvardhan D, Shimotohno K, Taira K, Nishikawa S. Isolation of RNA aptamers specific to the NS3 protein of hepatitis C virus from a pool of completely random RNA. Virology. 1997 Oct 27; 237(2):270-82. PMID: 9356339.
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      86. Machida K, Honda N, Matsumoto T, Yui N, Togawa T, Kubo A, Tsukatani Y, Oyamada H, Ishii K, Nishimaki H, Mori Y, Uno K, Murata H, Maruno H. [Diagnostic accuracy of 201T1 SPECT.MRI in brain diseases and inter-reader variance of diagnostic performance]. Kaku Igaku. 1996 Sep; 33(9):943-52. PMID: 8921662.
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      87. Nakamura T, Arai Y, Terada A, Kudoh K, Imamura K, Machida K, Kikuchi H, Takebe K. Dietary analysis of Japanese patients with chronic pancreatitis in stable conditions. J Gastroenterol. 1994 Dec; 29(6):756-62. PMID: 7874272.
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      88. Takahashi M, Machida K, Murata M, Misumi H, Hori E, Kawamura A, Tanaka H. Seasonal development of Leptotrombidium pallidum (Acari: Trombiculidae) observed by experimental rearing in the natural environment. J Med Entomol. 1993 Mar; 30(2):320-5. PMID: 8459408.
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      89. Sudo K, Maekawa M, Shioya M, Ikeda K, Takahashi N, Isogai Y, Li SS, Kanno T, Machida K, Toriumi J. Molecular analysis of genetic mutation in electrophoretic variant of human lactate dehydrogenase-A(M) subunit. Biochem Int. 1992 Sep; 27(6):1051-7. PMID: 1445373.
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      90. Takahashi M, Murata M, Machida K, Hori E, Kawamura A, Tanaka H. Aggregated distribution of infective spots composed of Leptotrombidium pallidum, highly prevalent with Rickettsia tsutsugamushi, demonstrated by sentinel voles, Microtus montebelli, on the ground. Jpn J Exp Med. 1990 Dec; 60(6):325-35. PMID: 2128945.
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      91. Sudo K, Maekawa M, Ikawa S, Machida K, Kitamura M, Li SS. A missense mutation found in human lactate dehydrogenase-B (H) variant gene. Biochem Biophys Res Commun. 1990 Apr 30; 168(2):672-6. PMID: 2334429.
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