Keigo Machida

Summary

Affiliation: University of Southern California
Country: USA

Publications

  1. pmc TLRs, Alcohol, HCV, and Tumorigenesis
    Keigo Machida
    Department of Molecular Microbiology and Immunology, 503B HMR, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
    Gastroenterol Res Pract 2010:518674. 2010
  2. pmc Cancer stem cells generated by alcohol, diabetes, and hepatitis C virus
    Keigo Machida
    Southern California Research Center for ALPD and Cirrhosis, Los Angeles, California, USA
    J Gastroenterol Hepatol 27:19-22. 2012
  3. pmc 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
    Keigo Machida
    Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
    J Immunol 185:6985-98. 2010
  4. pmc c-Jun mediates hepatitis C virus hepatocarcinogenesis through signal transducer and activator of transcription 3 and nitric oxide-dependent impairment of oxidative DNA repair
    Keigo Machida
    Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA
    Hepatology 52:480-92. 2010
  5. pmc Hepatitis C virus triggers mitochondrial permeability transition with production of reactive oxygen species, leading to DNA damage and STAT3 activation
    Keigo Machida
    Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, 90033, USA
    J Virol 80:7199-207. 2006
  6. pmc Reciprocal regulation by TLR4 and TGF-β in tumor-initiating stem-like cells
    Chia Lin Chen
    Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, California, USA
    J Clin Invest 123:2832-49. 2013
  7. pmc Hepatitis C virus infection activates the immunologic (type II) isoform of nitric oxide synthase and thereby enhances DNA damage and mutations of cellular genes
    Keigo Machida
    Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Ave, Los Angeles, CA 90033, USA
    J Virol 78:8835-43. 2004
  8. pmc Hepatitis C virus causes uncoupling of mitotic checkpoint and chromosomal polyploidy through the Rb pathway
    Keigo Machida
    Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, California 90033, USA
    J Virol 83:12590-600. 2009
  9. pmc Toll-like receptor 4 mediates synergism between alcohol and HCV in hepatic oncogenesis involving stem cell marker Nanog
    Keigo Machida
    Southern California Research Center for Alcoholic, Liver, and Pancreatic Diseases and Cirrhosis, and Department of Molecular Microbiology, University of Southern California, Keck School of Medicine, 2011 Zonal Avenue, Los Angeles, CA 90033, USA
    Proc Natl Acad Sci U S A 106:1548-53. 2009
  10. pmc Hepatitis C virus induces toll-like receptor 4 expression, leading to enhanced production of beta interferon and interleukin-6
    Keigo Machida
    Department of Molecular Microbiology and Immunology, USC Keck School of Medicine, 2011 Zonal Avenue, Los Angeles, CA 90033, USA
    J Virol 80:866-74. 2006

Collaborators

Detail Information

Publications30

  1. pmc TLRs, Alcohol, HCV, and Tumorigenesis
    Keigo Machida
    Department of Molecular Microbiology and Immunology, 503B HMR, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
    Gastroenterol Res Pract 2010:518674. 2010
    ..Synergism between alcohol and HCV may lead to liver tumorigenesis through TLR signaling...
  2. pmc Cancer stem cells generated by alcohol, diabetes, and hepatitis C virus
    Keigo Machida
    Southern California Research Center for ALPD and Cirrhosis, Los Angeles, California, USA
    J Gastroenterol Hepatol 27:19-22. 2012
    ..Taken together, Tlr4 may be a universal proto-oncogene responsible for the genesis of TLR4-NANOG dependent TISCs, and this pathway serves as a novel therapeutic target for HCC...
  3. pmc 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
    Keigo Machida
    Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
    J Immunol 185:6985-98. 2010
    ..These effects may explain the oncogenicity and immunological perturbation of HCV infection...
  4. pmc c-Jun mediates hepatitis C virus hepatocarcinogenesis through signal transducer and activator of transcription 3 and nitric oxide-dependent impairment of oxidative DNA repair
    Keigo Machida
    Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA
    Hepatology 52:480-92. 2010
    ..The core protein also suppresses apoptosis mediated by Fas ligand because of c-Jun-dependent Fas down-regulation...
  5. pmc Hepatitis C virus triggers mitochondrial permeability transition with production of reactive oxygen species, leading to DNA damage and STAT3 activation
    Keigo Machida
    Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, 90033, USA
    J Virol 80:7199-207. 2006
    ..These HCV studies thus identified ROS, along with the previously identified NO, as the primary inducers of DSBs and mitochondrial damage in HCV-infected cells...
  6. pmc Reciprocal regulation by TLR4 and TGF-β in tumor-initiating stem-like cells
    Chia Lin Chen
    Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, California, USA
    J Clin Invest 123:2832-49. 2013
    ..Taken together, these results suggest that the activated TLR4/NANOG oncogenic pathway is linked to suppression of cytostatic TGF-β signaling and could potentially serve as a therapeutic target for HCV-related HCC...
  7. pmc Hepatitis C virus infection activates the immunologic (type II) isoform of nitric oxide synthase and thereby enhances DNA damage and mutations of cellular genes
    Keigo Machida
    Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Ave, Los Angeles, CA 90033, USA
    J Virol 78:8835-43. 2004
    ..NO causes DNA breaks and enhances DNA mutation. This sequence of events provides a mechanism for HCV pathogenesis and oncogenesis...
  8. pmc Hepatitis C virus causes uncoupling of mitotic checkpoint and chromosomal polyploidy through the Rb pathway
    Keigo Machida
    Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, California 90033, USA
    J Virol 83:12590-600. 2009
    ..Taken together, these data suggest that HCV infection may inhibit the mitotic checkpoint to induce polyploidy, which likely contributes to neoplastic transformation...
  9. pmc Toll-like receptor 4 mediates synergism between alcohol and HCV in hepatic oncogenesis involving stem cell marker Nanog
    Keigo Machida
    Southern California Research Center for Alcoholic, Liver, and Pancreatic Diseases and Cirrhosis, and Department of Molecular Microbiology, University of Southern California, Keck School of Medicine, 2011 Zonal Avenue, Los Angeles, CA 90033, USA
    Proc Natl Acad Sci U S A 106:1548-53. 2009
    ..Taken together, our study demonstrates a TLR4-dependent mechanism of synergistic liver disease by HCV and alcohol and an obligatory role for Nanog, a TLR4 downstream gene, in HCV-induced liver oncogenesis enhanced by alcohol...
  10. pmc Hepatitis C virus induces toll-like receptor 4 expression, leading to enhanced production of beta interferon and interleukin-6
    Keigo Machida
    Department of Molecular Microbiology and Immunology, USC Keck School of Medicine, 2011 Zonal Avenue, Los Angeles, CA 90033, USA
    J Virol 80:866-74. 2006
    ..In conclusion, HCV infection directly induces TLR4 expression and thereby activates B cells, which may contribute to the host's innate immune responses...
  11. pmc Hepatitis C virus (HCV)-induced immunoglobulin hypermutation reduces the affinity and neutralizing activities of antibodies against HCV envelope protein
    Keigo Machida
    Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, 2011 Zonal Avenue, Los Angeles, CA 90033, USA
    J Virol 82:6711-20. 2008
    ..These results suggest that HCV infection could cause some anti-HCV-antibody-producing hybridoma B cells to make less-protective antibodies...
  12. pmc Transient activation of the PI3K-AKT pathway by hepatitis C virus to enhance viral entry
    Zhe Liu
    Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA
    J Biol Chem 287:41922-30. 2012
    ..These results provide important information for understanding HCV replication and pathogenesis and raised the possibility of targeting this cellular pathway to treat HCV patients...
  13. pmc Alcohol induces RNA polymerase III-dependent transcription through c-Jun by co-regulating TATA-binding protein (TBP) and Brf1 expression
    Shuping Zhong
    Department of Biochemistry and Molecular Biology and the Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90033, USA
    J Biol Chem 286:2393-401. 2011
    ..Together, these results identify a new class of genes that are regulated by alcohol through the co-regulation of TFIIIB components and define a central role for c-Jun in this process...
  14. pmc 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
    Samantha M Yeligar
    Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
    J Immunol 183:5964-76. 2009
    ..The identification of HIF-1alpha and AP-1 in ethanol-induced RANTES expression provides new strategies to ameliorate ethanol-induced inflammatory responses...
  15. pmc Hepatitis C virus E2-CD81 interaction induces hypermutation of the immunoglobulin gene in B cells
    Keigo Machida
    Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, 2011 Zonal Ave, Los Angeles, California 90033, USA
    J Virol 79:8079-89. 2005
    ....
  16. ncbi request reprint HCV core expression in hepatocytes protects against autoimmune liver injury and promotes liver regeneration in mice
    Hiroki Kawamura
    Department of Molecular Microbiology, USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA 90089 9176, USA
    Hepatology 44:936-44. 2006
    ..In conclusion, HCV core inhibits STAT1 and stimulates STAT3 activation, which protects infected hepatocytes from attack by the cell-mediated immune system and promotes their proliferation...
  17. pmc SYNCRIP (synaptotagmin-binding, cytoplasmic RNA-interacting protein) is a host factor involved in hepatitis C virus RNA replication
    Helene Minyi Liu
    Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA
    Virology 386:249-56. 2009
    ..These findings indicate that SYNCRIP has dual functions, participating in both RNA replication and translation in HCV life cycle...
  18. doi request reprint Hepatitis C virus infection of T cells inhibits proliferation and enhances fas-mediated apoptosis by down-regulating the expression of CD44 splicing variant 6
    Yasuteru Kondo
    Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, USA Division of Gastroenterology, Tohoku University, Sendai City
    J Infect Dis 199:726-36. 2009
    ..During T cell development and activation, transient expression of CD44 splicing variant 6 (CD44v6) plays a significant role...
  19. pmc Hepatitis C virus translation preferentially depends on active RNA replication
    Helene Minyi Liu
    Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
    PLoS ONE 7:e43600. 2012
    ..Our findings together indicate that the translation of HCV RNA is coupled to RNA replication and that the both processes may occur at the same subcellular membrane compartments, which we term the replicasome...
  20. pmc A super TLR agonist to improve efficacy of dendritic cell vaccine in induction of anti-HCV immunity
    Bangxing Hong
    Norris Comprehensive Cancer Center, Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA
    PLoS ONE 7:e48614. 2012
    ..Thus, the strategy capable of triggering and sustaining proinflammatory status of DCs may be used to boost efficiency of DC vaccine in preventing and combating the persistent infection of HCV or other chronic viruses...
  21. pmc Replication of hepatitis C virus RNA on autophagosomal membranes
    Donna Sir
    Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    J Biol Chem 287:18036-43. 2012
    ..These results indicate that HCV induces autophagosomes via a Class III PI3K-independent pathway and uses autophagosomal membranes as sites for its RNA replication...
  22. pmc Morphogens and hepatic stellate cell fate regulation in chronic liver disease
    Hidekazu Tsukamoto
    Southern California Research Center for ALPD and Cirrhosis, University of Southern California Keck School of Medicine, Los Angeles, CA, USA
    J Gastroenterol Hepatol 27:94-8. 2012
    ..Implications of HSC-derived morphogens in these possibilities are discussed...
  23. pmc Ethanol-induced HO-1 and NQO1 are differentially regulated by HIF-1alpha and Nrf2 to attenuate inflammatory cytokine expression
    Samantha M Yeligar
    Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
    J Biol Chem 285:35359-73. 2010
    ..Additionally, up-regulation of HO-1 protects the liver from excessive formation of inflammatory cytokines. These studies provide novel therapeutic targets to ameliorate alcohol induced inflammation and liver injury...
  24. ncbi request reprint Hepatitis C virus infects T cells and affects interferon-gamma signaling in T cell lines
    Yasuteru Kondo
    Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, 2011 Zonal Avenue, Los Angeles, CA 90033, USA
    Virology 361:161-73. 2007
    ..In conclusion, HCV could infect and transiently replicate in T cells and that HCV replication suppressed the IFN-gamma/STAT-1/T-bet signaling due to the reduction of STAT-1 and inhibition of its activation (phosphorylation)...
  25. pmc The TBC1D15 oncoprotein controls stem cell self-renewal through destabilization of the Numb-p53 complex
    Douglas E Feldman
    Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA
    PLoS ONE 8:e57312. 2013
    ..The profound deregulation of TBC1D15 expression exhibited in a diverse array of patient tumors underscores its proposed function as an oncoprotein...
  26. doi request reprint Mouse intragastric infusion (iG) model
    Akiko Ueno
    Southern California Research Center for ALPD and Cirrhosis, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
    Nat Protoc 7:771-81. 2012
    ....
  27. pmc Pluripotency factor-mediated expression of the leptin receptor (OB-R) links obesity to oncogenesis through tumor-initiating stem cells
    Douglas Edmund Feldman
    Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
    Proc Natl Acad Sci U S A 109:829-34. 2012
    ..Differential responses to extrinsic, adipocyte-derived cues may promote the expansion of tumor cell subpopulations and contribute to oncogenesis...
  28. pmc Hepatitis C virus induces a mutator phenotype: enhanced mutations of immunoglobulin and protooncogenes
    Keigo Machida
    Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, 2011 Zonal Avenue, Los Angeles, CA 90033, USA
    Proc Natl Acad Sci U S A 101:4262-7. 2004
    ..These results indicate that HCV induces a mutator phenotype and may transform cells by a hit-and-run mechanism. This finding provides a mechanism of oncogenesis for an RNA virus...
  29. pmc Inhibition of RIG-I-mediated signaling by Kaposi's sarcoma-associated herpesvirus-encoded deubiquitinase ORF64
    Kyung Soo Inn
    Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
    J Virol 85:10899-904. 2011
    ..This study suggests that RIG-I plays a potential role in sensing KSHV infection and that KSHV ORF64 DUB counteracts RIG-I signaling...
  30. doi request reprint "Second hit" models of alcoholic liver disease
    Hidekazu Tsukamoto
    Southern California Research Center for ALPD and Cirrhosis, Keck School of Medicine of University of Southern California, Los Angeles, California 90033, USA
    Semin Liver Dis 29:178-87. 2009
    ..Additionally, animal models of comorbidities are urgently needed particularly for synergistic liver disease and oncogenesis caused by alcohol, obesity, and hepatitis virus...

Research Grants2

  1. Nanog-positive cancer stem cells in and liver oncogenesis by alcohol and HCV
    Keigo Machida; Fiscal Year: 2009
    ..The goal of this proposal is to understand how HCV and alcohol induces liver cancer so that better prevention and treatment can be found. ..
  2. Nanog-positive cancer stem cells in and liver oncogenesis by alcohol and HCV
    Keigo Machida; Fiscal Year: 2010
    ..The goal of this proposal is to understand how HCV and alcohol induces liver cancer so that better prevention and treatment can be found. ..