The HARA LaboratoryMicrobiology & Immunology



  1. Sumida K, Doi T, Obayashi K, Chiba Y, Nagasaka S, Ogino N, Miyagawa K, Baba R, Morimoto H, Hara H, Terabayashi T, Ishizaki T, Harada M, Endo M. Caspase-4 has a role in cell division in epithelial cells through actin depolymerization. Biochemical and Biophysical Research Communications 2024, 695, 149394.
  2. Tanishita Y, Sekiya H, Inohara N, Tsuchiya K, Mitsuyama M, Núñez G, ※Hara H. Listeria Toxin Promotes Phosphorylation of the Inflammasome Adaptor ASC through Lyn and Syk to Exacerbate Pathogen Expansion. Cell Reports 2022, 38, 110414. ※Corresponding author
  3. Tsuchiya K, Hosojima S, Hara H, Kushiyama H, Mahib M. R., Kinoshita T, Suda T. Gasdermin D mediates the maturation and release of IL-1α downstream of inflammasomes. Cell Reports 2021, 34, 108887.
  4. Fang R, Uchiyama R, Sakai S, Hara H, Tsutsui H, Suda T, Mitsuyama M, Kawamura I, Tsuchiya K. ASC and NLRP3 maintain innate immune homeostasis in the airway through an inflammasome-independent mechanism. Mucosal Immunology 2019, 12, 1092-1103.
  5. Hara H, Seregin SS, Yang D, Fukase K, Chamaillard M, Alnemri ES, Inohara N, Chen GY, Núñez G. The NLRP6 inflammasome recognizes lipoteichoic acid and regulates Gram-positive pathogen infection. Cell 2018, 175, 1651-1664.  Corresponding author
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  6. Sakamoto K, Kim YG, Hara H, Kamada N, Caballero-Flores G, Tolosano E, Soares MP, Puente JL, Inohara N, Núñez G. IL-22 controls heme/Iron-dependent nutritional immunity against systemic bacterial infections. Science Immunology 2017, eaai8371.
  7. Conos SA, Chen KW, De Nardo D, Hara H, Whitehead L, Núñez G, Masters SL, Murphy JM, Schroder K, Vaux DL, Lawlor KE, Lindqvist LM, Vince JE. Active MLKL triggers the NLRP3 inflammasome in a cell-intrinsic manner. Proceedings of the National Academy of Sciences of the U S A 2017, 114, 961-969.
  8. Hashino M, Tachibana M, Nishida T, Hara H, Tsuchiya K, Mitsuyama M, Watanabe K, Shimizu T, Watarai M. Inactivation of the MAPK signaling pathway by Listeria monocytogenes infection promotes trophoblast giant cell death. Frontiers in Microbiology 2015, 6, 1145.
  9. Tsuchiya K, Hara H, Fang R, Hernandez-Cuellar E, Sakai S, Daim S, Chen X, Dewamitta SR, Qu H, Mitsuyama M, Kawamura I. The adaptor ASC exacerbates lethal Listeria monocytogenes infection by mediating IL-18 production in an inflammasome-dependent and -independent manner. European Journal of Immunology 2014, 44, 3696-3707.
  10. Fang R, Hara H, Sakai S, Hernandez-Cuellar E, Mitsuyama M, Kawamura I, Tsuchiya K. Type I interferon signaling regulates activation of the absent in melanoma 2 inflammasome during Streptococcus pneumoniae infection. Infection and Immunity 2014, 82, 2310-2317.
  11. Yang R, Xi C, Sita DR, Sakai S, Tsuchiya K, Hara H, Shen Y, Qu H, Fang R, Mitsuyama M, Kawamura I. The RD1 locus in the Mycobacterium tuberculosis genome contributes to the maturation and secretion of IL-1α from infected macrophages through the elevation of cytoplasmic calcium levels and calpain activation. Pathogens and Disease2014, 70, 51-60.
  12. Hara H, Tsuchiya K, Kawamura I, Fang R, Hernandez-Cuellar E, Shen Y, Mizuguchi J, Schweighoffer E, Tybulewicz V, Mitsuyama M. Phosphorylation of the adaptor ASC acts as a molecular switch that controls the formation of speck-like aggregates and inflammasome activity. Nature Immunology 2013, 14, 1247-1255.
  13. Hernandez-Cuellar E, Tsuchiya K, Hara H, Fang R, Sakai S, Kawamura I, Akira S, Mitsuyama M. Nitric oxide inhibits the NLRP3 inflammasome. Journal of Immunology 2012, 189, 5113-5117.
  14. Tanaka T, Takahashi K, Yamane M, Tomida S, Nakamura S, Oshima K, Niwa A, Nishikomori R, Kambe N, Hara H, Mitsuyama M, Morone N, Heuser JE, Yamamoto T, Watanabe A, Sato-Otsubo A, Ogawa S, Asaka I, Heike T, Yamanaka S, Nakahata T, Saito MK. Induced pluripotent stem cells from CINCA syndrome patients as a model for dissecting somatic mosaicism and drug discovery. Blood 2012, 120, 1299-1308.
  15. Yamamoto T, Hara H, Tsuchiya K, Sakai S, Fang R, Matsuura M, Nomura T, Sato F, Mitsuyama M, Kawamura I. Listeria monocytogenes strain-specific impairment of the TetR regulator underlies the drastic increase in cyclic di-AMP secretion and beta interferon-inducing ability. Infection and Immunity 2012, 80, 2323-2332.
  16. Sugata K, Satou Y, Yasunaga J, Hara H, Ohshima K, Utsunomiya A, Mitsuyama M, Matsuoka M. HTLV-1 bZIP factor impairs cell-mediated immunity by suppressing production of Th1 cytokines. Blood 2012, 119, 434-444.
  17. Fang R, Tsuchiya K, Kawamura I, Shen Y, Hara H, Sakai S, Yamamoto T, Fernandes-Alnemri T, Yang R, Hernandez-Cuellar E, Dewamitta SR, Xu Y, Qu H, Alnemri ES, Mitsuyama M. Critical roles of ASC inflammasomes in caspase-1 activation and host innate resistance to Streptococcus pneumoniae infection. Journal of Immunology 2011, 187, 4890-4899.
  18. Daim S, Kawamura I, Tsuchiya K, Hara H, Kurenuma T, Shen Y, Dewamitta SR, Sakai S, Nomura T, Qu H, Mitsuyama M. Expression of the Mycobacterium tuberculosis PPE37 protein in Mycobacterium smegmatis induces low tumour necrosis factor alpha and interleukin 6 production in murine macrophages. Journal of Medical Microbiology 2011, 60, 582-591.
  19. Nagahama M, Itohayashi Y, Hara H, Higashihara M, Fukatani Y, Takagishi T, Oda M, Kobayashi K, Nakagawa I, Sakurai J. Cellular vacuolation induced by Clostridium perfringens epsilon-toxin. FEBS Journal 2011, 278, 3395-3407.
  20. Tsuchiya K, Hara H, Kawamura I, Nomura T, Yamamoto T, Daim S, Dewamitta SR, Shen Y, Fang R, Mitsuyama M. Involvement of absent in melanoma 2 in inflammasome activation in macrophages infected with Listeria monocytogenes. Journal of Immunology 2010, 185, 1186-1195.
  21. Shen Y, Kawamura I, Nomura T, Tsuchiya K, Hara H, Dewamitta SR, Sakai S, Qu H, Daim S, Yamamoto T, Mitsuyama M. Toll-like receptor 2- and MyD88-dependent phosphatidylinositol 3-kinase and Rac1 activation facilitates the phagocytosis of Listeria monocytogenes by murine macrophages. Infection and Immunity 2010, 78, 2857-2867.
  22. Dewamitta SR, Nomura T, Kawamura I, Hara H, Tsuchiya K, Kurenuma T, Shen Y, Daim S, Yamamoto T, Qu H, Sakai S, Xu Y, Mitsuyama M. Listeriolysin O-dependent bacterial entry into the cytoplasm is required for calpain activation and interleukin-1 alpha secretion in macrophages infected with Listeria monocytogenes. Infection and Immunity 2010, 78, 1884-1894.
  23. Kurenuma T, Kawamura I, Hara H, Uchiyama R, Daim S, Dewamitta SR, Sakai S, Tsuchiya K, Nomura T, Mitsuyama M. The RD1 locus in the Mycobacterium tuberculosis genome contributes to activation of caspase-1 via induction of potassium ion efflux in infected macrophages. Infection and Immunity 2009, 77, 3992-4001.
  24. Hara H, Tsuchiya K, Nomura T, Kawamura I, Shoma S, Mitsuyama M. Dependency of caspase-1 activation induced in macrophages by Listeria monocytogenes on cytolysin, listeriolysin O, after evasion from phagosome into the cytoplasm. Journal of Immunology 2008, 180, 7859-7868.
  25. Shoma S, Tsuchiya K, Kawamura I, Nomura T, Hara H, Uchiyama R, Daim S, Mitsuyama M. Critical involvement of pneumolysin in production of interleukin-1alpha and caspase-1-dependent cytokines in infection with Streptococcus pneumoniae in vitro: a novel function of pneumolysin in caspase-1 activation. Infection and Immunity 2008, 76, 1547-1557.
  26. Hara H, Kawamura I, Nomura T, Tominaga T, Tsuchiya K, Mitsuyama M. Cytolysin-dependent escape of the bacterium from the phagosome is required but not sufficient for induction of the Th1 immune response against Listeria monocytogenes infection: distinct role of Listeriolysin O determined by cytolysin gene replacement. Infection and Immunity 2007, 75, 3791-3801.
  27. Nagahama M, Hara H, Fernandez-Miyakawa M, Itohayashi Y, Sakurai J. Oligomerization of Clostridium perfringens epsilon-toxin is dependent upon membrane fluidity in liposomes. Biochemistry 2006, 45, 296-302.


  1. Matsuda Y, Yamauchi H, ※Hara H. Activation of inflammasomes and mechanisms for intracellular recognition of Listeria monocytogenes. Microbiology and Immunology 2023, 67, 429-437. Corresponding author
  2. He Y, Hara H, Núñez G. Mechanism and Regulation of NLRP3 Inflammasome Activation. Trends in Biochemical Sciences 2016, 41, 1012-1021.
  3. Tsuchiya K and Hara H. The inflammasome and its regulation. Critical Reviews in Immunology 2014, 34, 41-80.


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