Faculty

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Keigo Machida, PhD
Associate Professor of Molecular Microbiology & Immunology
Molecular Microbiology and Immunology
HMR 503A 2011 Zonal Avenue Health Sciences Campus Los Angeles
+1 323 442 2692

Publications

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 L. Loss of the TGF-ß Effector ß2SP Promotes Genomic Instability. Hepatology. 2016 Nov 5. View in: PubMed

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. View in: PubMed

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 1; 126(2):527-42. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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 1; 128(11):761-74. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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 1; 123(7):2832-49. View in: PubMed

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. View in: PubMed

Kondo Y, Uno K, Machida K, Terajima M. PPARs and Liver Disease. PPAR Res. 2013; 2013:896412. View in: PubMed

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. View in: PubMed

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 7; 287(50):41922-30. View in: PubMed

Montfort Cv, 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. View in: PubMed

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. View in: PubMed

Ueno A, Lazaro R, Wang PY, Higashiyama R, Machida K, Tsukamoto H. Mouse intragastric infusion (iG) model. Nat Protoc. 2012 Apr; 7(4):771-81. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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 1; 185(11):6985-98. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

Szabo G, Billiar TR, Machida K, Crispe IN, Seki E. Toll-like receptor signaling in liver diseases. Gastroenterol Res Pract. 2010; 2010:971270. View in: PubMed

Machida K. TLRs, Alcohol, HCV, and Tumorigenesis. Gastroenterol Res Pract. 2010; 2010:518674. View in: PubMed

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. View in: PubMed

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 1; 183(9):5964-76. View in: PubMed

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. View in: PubMed

Tsukamoto H, Machida K, Dynnyk A, Mkrtchyan H. "Second hit" models of alcoholic liver disease. Semin Liver Dis. 2009 May; 29(2):178-87. View in: PubMed

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. View in: PubMed

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 1; 199(5):726-36. View in: PubMed

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 3; 106(5):1548-53. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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