Ohtani Lab, Department of Pathophysiology, Osaka City University Graduate School of Medicine

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Publications

Original papers (selected)

  1. Choi Y, Takasugi M, Takemura K, Yoshida Y, Kamiya T, Adachi J, Tsuruta D, Ohtani N. Characterization of Transcriptomic and Proteomic Changes in the Skin after Chronic Fluocinolone Acetonide Treatment. Biomolecules. 2022;12(12):1822. doi: 10.3390/biom12121822.
  2. Cheng Y, Yamagishi R, Nonaka Y, Sato-Matsubara M, Kawada N, Ohtani N. Non-heat-stressed method to isolate hepatic stellate cells from highly steatotic tumor-bearing liver using CD49a. Cell Mol Gastroenterol Hepatol. 2022: S2352-345X(22)00164-3. doi: 10.1016/j.jcmgh.2022.07.006.
  3. Yukawa-Muto Y, Kamiya T, Fujii H, Mori H, Toyoda A, Sato I, Konishi Y, Hirayama A, Hara E, Fukuda S, Kawada N, Ohtani N. Distinct responsiveness to rifaximin in patients with hepatic encephalopathy depends on functional gut microbial species. Hepatol Commun. 2022;6(8):2090-2104. doi: 10.1002/hep4.1954.
  4. Yamagishi R, Kamachi F, Nakamura M, Yamazaki S, Kamiya T, Takasugi M, Cheng Y, Nonaka Y, Yukawa-Muto Y, Thuy LTT, Harada Y, Arai T, Loo T-M, Yoshimoto S, Ando T, Nakajima M, Taguchi H, Ishikawa T, Akiba H, Miyake S, Kubo M, Iwakura Y, Fukuda S, Chen W-Y, Kawada N, Rudensky A, Nakae S, Hara E, Ohtani N. Gasdermin D-mediated release of IL-33 from senescent hepatic stellate cells promotes obesity-associated hepatocellular carcinoma.
    Science Immunology 7, doi: 10.1126/sciimmunol.abl7209. (2022)
    Free access to this paper
    https://www.science.org/stoken/author-tokens/ST-578/full
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  5. Hoang DV, Thuy LTT, Hai H, Hieu VN, Kimura K, Oikawa D, Ikura Y, Dat NQ, Hoang TH, Sato-Matsubara M, Dong MP, Hanh NV, Uchida-Kobayashi S, Tokunaga F, Kubo S, Ohtani N, Yoshizato K, Kawada N. Cytoglobin attenuates pancreatic cancer growth via scavenging reactive oxygen species. Oncogenesis 11(1):23. doi: 10.1038/s41389-022-00389-4. (2022)
  6. Wang B, Varela-Eirin M, Brandenburg SM, Hernandez-Segura A, van Vliet T, Jongbloed EM, Wilting SM, Ohtani N, Jager A, Demaria M.
    Pharmacological CDK4/6 inhibition reveals a p53-dependent senescent state with restricted toxicity.
    EMBO J. 2022 Mar 15;41(6):e108946. doi: 10.15252/embj.2021108946.
  7. Konishi Y, Okumura S, Matsumoto T, Itatani Y, Nishiyama T, Okazaki Y, Shibutani M, Ohtani N, Nagahara H, Obama K, Ohira M, Sakai Y, Nagayama S, Hara E.
    Development and evaluation of a colorectal cancer screening method using machine learning-based gut microbiota analysis.
    Cancer Med. 2022 Mar 22. doi: 10.1002/cam4.4671.
  8. Takada N, Takasugi M, Nonaka Y, Kamiya T, Takemura K, Satoh J, Ito S, Fujimoto K, Uematsu S, Yoshida K, Morita T, Nakamura H, Uezumi A, Ohtani N.
    Galectin-3 promotes the adipogenic differentiation of PDGFRα+ cells and ectopic fat formation in regenerating muscle.
    Development. 2022 Feb 1;149(3):dev199443. doi: 10.1242/dev.199443.
  9. Okumura S, Konishi Y, Narukawa M, Sugiura Y, Yoshimoto S, Arai Y, Sato S, Yoshida Y, Tsuji S, Uemura K, Wakita M, Matsudaira T, Matsumoto T, Kawamoto S, Takahashi A, Itatani Y, Miki H, Takamatsu M, Obama K, Takeuchi K, Suematsu M, Ohtani N, Fukunaga Y, Ueno M, Sakai Y, Nagayama S, Hara E.
    Gut bacteria identified in colorectal cancer patients promote tumourigenesis via butyrate secretion.
    Nat Commun. 2021 Sep 28;12(1):5674. doi: 10.1038/s41467-021-25965-x.
  10. Fudaba M, Kamiya T, Tachibana D, Koyama M, Ohtani N.
    Bioinformatics Analysis of Oral, Vaginal, and Rectal Microbial Profiles during Pregnancy: A Pilot Study on the Bacterial Co-Residence in Pregnant Women.
    Microorganisms. 2021 May 11;9(5):1027. doi: 10.3390/microorganisms9051027.
    ⇒第73回日本産科婦人科学会学術講演会・JSOG Congress Encouragement Awardを受賞しました
  11. Okubo K, Kitagawa Y, Hosokawa N, Umezawa M, Kamimura M, Kamiya T, Ohtani N, Soga K.
    Visualization of quantitative lipid distribution in mouse liver through near-infrared hyperspectral imaging
    Biomed Opt Express 2021;12:823-835. doi: 10.1364/BOE.413712.
    https://www.osaka-cu.ac.jp/ja/news/2020/210324
    https://medium.com/the-reading-frame/a-non-invasive-look-at-fat-distribution-in-the-liver-d8003756fe8a
  12. Wakita M, Takahashi A, Sano O, Loo TM, Imai Y, Narukawa M, Iwata H, Matsudaira T,
    Kawamoto S, Ohtani N, Yoshimori T, Hara E.
    A BET Family Protein Degrader Provokes Senolysis by Targeting NHEJ and Autophagy in Senescent Cells.
    Nat Communcations 2020, 11:1935. doi: 10.1038/s41467-020-15719-6.
  13. Taguchi T, Kotelsky A, Takasugi M, Chang M, Ke Z, Betancourt M, Buckley MR, Zuscik M, Seluanov A, Gorbunova V.
    Naked mole‐rats are extremely resistant to post‐traumatic osteoarthritis.
    Aging Cell. 2020 Nov; 19(11): e13255. Published online 2020 Oct 28. doi: 10.1111/acel.13255
  14. Rezazadeh S, Yang D, Biashad SA, Firsanov D, Takasugi M, Gilbert M, Tombline G, Bhanu NV, Garcia BA, Seluanov A, Gorbunova V.
    SIRT6 mono-ADP ribosylates KDM2A to locally increase H3K36me2 at DNA damage sites to inhibit transcription and promote repair.
    Aging (Albany NY) 2020 Jun 30; 12(12): 11165–11184. Published online 2020 Jun 25. doi: 10.18632/aging.103567
  15. Takasugi M, Firsanov D, Tombline G, Ning H, Ablaeva J, Seluanov A, Gorbunova V.
    Naked mole-rat very-high-molecular-mass hyaluronan exhibits superior cytoprotective properties.
    Nat Commun. 2020; 11: 2376. Published online 2020 May 12. doi: 10.1038/s41467-020-16050-w
  16. Hojo H, Yashiro Y, Noda Y, Ogami K, Yamagishi R, Okada S, Hoshino S, Suzuki T.
    The RNA-binding protein QKI-7 recruits the poly(A) polymerase GLD-2 for 3′ adenylation and selective stabilization of microRNA-122.
    J Biol Chem. 2020 Jan 10; 295(2): 390–402. Published online 2019 Dec 1. doi: 10.1074/jbc.RA119.011617
  17. Iwamoto M, Saso W, Sugiyama R, Ishii K, Ohki M, Nagamori S, Suzuki R, Aizaki H, Ryo A, Yun JH, Park SY, Ohtani N, Muramatsu M, Iwami S, Tanaka Y, Sureau C, Wakita T, Watashi K.
    Epidermal growth factor receptor is a host-entry cofactor triggering hepatitis B virus internalization.
    Proc Natl Acad Sci U S A. 2019 pii: 201811064. doi: 10.1073/pnas.1811064116.
  18. Ohashi H, Nishioka K, Nakajima S, Kim S, Suzuki R, Aizaki H, Fukasawa M, Kamisuki S, Sugawara F, Ohtani N, Muramatsu M, Wakita T, Watashi K.
    The aryl hydrocarbon receptor-cytochrome P450 1A1 pathway controls lipid accumulation and enhances the permissiveness for hepatitis C virus assembly.
    J Biol Chem. 2018 Dec 21;293(51):19559-19571. doi: 10.1074/jbc.RA118.005033.
  19. Takahashi A, Loo TM, Okada R, Kamachi F, Watanabe Y, Wakita M, Watanabe S, Kawamoto S, Miyata K, Barber GN, Ohtani N, Hara E.　Downregulation of cytoplasmic DNases is implicated in cytoplasmic DNA accumulation and SASP in senescent cells.
    Nature Communications 9:1249. doi: 10.1038/s41467-018-03555-8. (2018)
  20. Loo TM, Kamachi F, Watanabe Y, Yoshimoto S, Kanda H, Arai Y, Nakajima-Takagi Y, Iwama A, Koga T, Sugimoto Y, Ozawa T, Nakamura M, Kumagai M, Watashi K, Taketo MM, Aoki T, Narumiya S, Oshima M, Arita M, Hara E, Ohtani N. Gut Microbiota Promotes Obesity-Associated Liver Cancer through PGE2-Mediated Suppression of Antitumor Immunity.
    Cancer Discovery 7, 522-538 (2017) doi:10.1158/2159-8290.CD-16-0932.
  21. Kaneko M, Watashi K, Kamisuki S, Matsunaga H, Iwamoto M, Kawai F, Ohashi H, Tsukuda S, Shimura S, Suzuki R, Aizaki H, Sugiyama M, Park SY, Ito T, Ohtani N, Sugawara F, Tanaka Y, Mizokami M, Sureau C, Wakita T. A Novel Tricyclic Polyketide, Vanitaracin A, Specifically Inhibits the Entry of Hepatitis B and D Viruses by Targeting Sodium Taurocholate Cotransporting Polypeptide.
    Journal of Virology 89, 11945-11953 (2015)
  22. Sato S, Kawamata Y, Takahashi A, Imai Y, Hanyu A, Okuma A, Takasugi M, Yamakoshi K, Sorimachi H, Kanda H, Ishikawa Y, Sone S, Nishioka Y, Ohtani N, Hara E. Ablation of the p16INK4a tumour suppressor reverses ageing phenotypes of klotho mice.
    Nature Communications 6, 7035 (2015)
  23. Yamakoshi K, Katano S, Iida M, Kimura H, Okuma A, Ikemoto-Uezumi M, Ohtani N, Hara E, Maruyama M. Dysregulation of the Bmi-1/p16Ink4a pathway provokes an aging-associated decrease in submandibular gland function.
    Aging Cell 14, 616-624 (2015)
  24. Demaria M, Ohtani N, Youssef SA, Rodier F, Toussaint W, Mitchell JR, Laberge R-M, Jan Vijg J, Van Steeg H, Dollé MET, Hoeijmakers JHJ, de Bruin A, Hara E, Campisi J. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA.
    Developmental Cell31,722-33.　(2014)
  25. Johmura Y, Shimada M, Misaki T, Naiki-Ito A, Miyoshi H, Motoyama N, Ohtani N, Hara E, Nakamura M, Morita A, Takahashi S, Nakanishi M. Necessary and Sufficient Role for a Mitosis Skip in Senescence Induction.
    Molecular Cell 55, 1–12, (2014)
  26. Imai Y, Takahashi A, Hanyuu A, Hori S, Sato S, Naka K, Hirao A, Ohtani N, Hara E. Crosstalk between the RB-pathway and AKT signaling forms a Quiescence-Senescence switch.
    Cell Reports 7:194-207, (2014)
  27. Yoshimoto S, Loo TM, Atarashi K, Kanda H, Sato S, Oyadomari S, Iwakura Y, Oshima K, Morita H, Hattori M, Honda K, Ishikawa Y, Hara E, Ohtani N. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome.
    Nature 499,97-101 (2013)
  28. Saito K, Takigawa N, Ohtani N, Iioka H, Tomita Y, Ueda R, Fukuoka J, Kuwahara K, Ichihara E, Kiura K, Kondo E. Antitumor Impact of p14ARF on Gefitinib-Resistant Non-Small Cell Lung Cancers.
    Molecule Cancer Therapeutics 12, 1616-28　(2013)
  29. Takahashi A, Imai Y, Yamakoshi K, Kuninaka S, Ohtani N, Yoshimoto S, Hori S, Tachibana M, Anderton E, Takeuchi T, Shinkai Y, Peters G, Saya H, Hara E. DNA Damage Signaling Triggers Degradation of Histone Methyltransferases through APC/CCdh1 in Senescent Cells.
    Molecular Cell 45, 123-131 (2012).
  30. Takeuchi S, Takahashi A, Motoi N, Yoshimoto S, Tajima T, Yamakoshi K, Hirao A, Yanagi S, Fukami K, Ishikawa Y, Sone S., Hara E. and Ohtani N. Intrinsic cooperation between p16Ink4a and p21Waf1/Cip1 in the onset of cellular senescence and tumor suppression in vivo.
    Cancer Research 70, 9381-9390 (2010).
  31. Yamakoshi K, Takahashi A, Hirota F, Nakayama R, Ishimaru N, Kubo Y, J. Mann D. J, Ohmura M, Hirao A, Saya H, Arase S,Hayashi Y, Nakao K,Matsumoto M, Ohtani N, and Hara E. Real –time in vivo imaging of p16Ink4a reveals cross talk with p53.
    Journal of Cell Biology 186, 393-407 (2009)
  32. Ohtani N, Imamura Y., Yamakoshi K., Hirota F., Nakayama R., Kubo Y., Takahasi A., Ishimaru N., Hirao A., Mann DJ., Hayashi Y., Arase S., Matusmoto M., Nakao K. and Hara E. Visualizing the dynamics of p21Waf/Cip1 cyclin-dependent kinase inhibitor expression in living animals.
    Proceedings of the National Academy of Sciences of USA 104, 15034-15039, (2007)
  33. Takahashi A, Ohtani N., Yamakoshi, K., Iida, S., Tahara, H., Nakayama, K., Nakayama, K.I., Ide, T., Saya, H. and Hara E. Mitogenic signalling and the p16INK4a/Rb pathway co-operate to enforce irreversible cellular senescence.
    Nature Cell Biology 8, 1291-1297, (2006)
  34. Murao, K., Kubo, Y., Ohtani N., Hara, E., and Arase S. Epigenetic abnormalities in cutaneous squamous cell carcinomas: Frequent inactivation of the RB1/p16 and p53 pathways.
    British Journal of Dermatology 155, 999-1005, (2006)
  35. Maehara K, Yamakoshi K, Ohtani N, Kubo Y, Takahashi A, Arase S, Jones N and Hara E. Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53.
    Journal of Cell Biology 168, 553-560, (2005)
  36. Ohtani N, Brennan P, Gaubatz S, Sanij E, Hertzog P, Wolvetang E, Ghysdeal J, Rowe M and Hara E. Epstein Barr virus LMP1 blocks p16INK4a/RB-pathway by promoting nuclear export of E2F4/5.
    Journal of Cell Biology 162, 173-183, (2003)
  37. Ohtani N, Zebedee Z, Huot TJ, Stinson JA, Sugimoto M, Ohashi Y, Sharrocks AD, Peters G and Hara E. Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence.
    Nature 409, 1067-70, (2001)
  38. Sugimoto M, Nakamura T, Ohtani N, Hampson L, Hampson IN, Shimamoto A, Furuichi Y,　Okumura K, Niwa S, Taya Y and Hara E. Regulation of CDK4 activity by a novel CDK4-binding protein, p34SEI-1.
    Genes & Development 13, 3027-33, (1999)
  39. Hanai J, Chen LF, Kanno T, Ohtani N, Kim WY, Guo WH, Imamura T, Ishidou Y, Fukuchi M, Shi MJ, Stavnezer J, Kawabata M, Miyazono K and Ito Y. Interaction and functional cooperation of PEBP2/CBF with Smads: Synergistic induction of the immunoglobulin germline Calpha promoter.
    Journal of Biological Chemistry 74, 31577-82, (1999)

Scientific reviews

  1. Kamiya T, Ohtani N.
    The role of immune cells in the liver tumor microenvironment: an involvement of gut microbiota-derived factors.
    Int Immunol. 2022, doi: 10.1093/intimm/dxac020.
  2. Takasugi M, Yoshida Y, Ohtani N.
    Cellular senescence and the tumor microenvironment.
    Mol Oncol. 2022, doi: 10.1002/1878-0261.13268.
  3. Ohtani N.
    The roles and mechanisms of senescence-associated secretory phenotype (SASP): can it be controlled by senolysis?
    Inflamm Regen. 2022 Apr 2;42(1):11. doi: 10.1186/s41232-022-00197-8.
  4. Takasugi M, Yoshida Y, Hara E, Ohtani N.
    The role of cellular senescence and SASP in tumour microenvironment.
    FEBS J. 2022 Feb 2. doi: 10.1111/febs.16381.
  5. Ohtani N, Hara E.
    Gut-liver axis-mediated mechanism of liver cancer: A special focus on the role of gut microbiota.
    Cancer Sci. 2021 Nov;112(11):4433-4443. doi: 10.1111/cas.15142.
  6. Gorbunova V, Takasugi M, Seluanov A.
    Hyaluronan goes to great length.
    Cell Stress. 2020 Sep; 4(9): 227–229. Published online 2020 Jul 17. doi: 10.15698/cst2020.09.231
  7. Ohtani N and Kawada N
    The Role of Gut–Liver Axis in Liver Inflammation, Fibrosis, and Cancer:
    A Special Focus on Gut Microbiota Relationship
    Hepatology Communications 2019, 3: 456-470. Review
  8. Watanabe S, Kawamoto S, Ohtani N, Hara E.
    Impact of senescence-associated secretory phenotype and its potential as a therapeutic target for senescence-associated diseases.
    Cancer Sci. 2017 Apr;108(4):563-569. doi: 10.1111/cas.13184. Epub 2017 Apr 18. Review.
  9. Ohtani N.
    Microbiome and cancer.
    Seminar in Immunopathology 37:65-72 (2015). Review
  10. Ohtani N, Yoshimoto S, Hara E.
    Obesity and cancer: a gut microbial connection.
    Cancer Research 74:1885-9, (2014). Review
  11. Ohtani N, Hara E.
    Roles and mechanisms of cellular senescence in regulation of tissue homeostasis.
    Cancer Science 104, 525-30 (2013) Review
  12. Ohtani N, Takahashi A, Mann DJ, Hara E.
    Cellular senescence: a double-edged sword in the fight against cancer.
    Experimental Dermatology (2012) Suppl 1:1-4, 2012 Review
  13. Ohtani N , Yamakoshi K, Takahashi A, and Hara E.
    Real-time in vivo imagingof p16Ink4agene expression: a new approach to study senescence stress signaling in living animals.
    Cell Division 5,1, doi:10.1186/1747-1028-5-1 (2010) Review
  14. Ohtani N, Mann D. J and Hara E.
    Cellular senescence: Its role in tumor suppression and aging.
    Cancer Science 100, 792-797 (2009) Review
  15. Takahashi A, Ohtani N, and Hara E.
    Irreversibility of cellular senescence: dual roles of p16INK4a/Rb-pathway in cell cycle control.
    Cell Division 2:10, doi:10.1186/1747-1028-2-10, 2007 Review

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