発表論文

*Corresponding author
*Kawamoto, S., Uemura, K., Hori, N., Takayasu, L., Konishi, Y., Katoh, K., Matsumoto, T., Suzuki, M., Sakai, Y., Matsudaira, T., Adachi, T., Ohtani, N., Standley, D.M., Suda, W., Fukuda, S. & *Hara, E.
Bacterial induction of B-cell senescence promotes age-related changes in the gut microbiota.
Nature Cell Biol. 25: 865-876 (2023)
(Selected for News & Views)
Tsuji, S., Minami, S., Hashimoto, R., Konishi, Y., Suzuki, T., Kondo, T., Sasai, M., Torii, S., Ono, C., Shichinohe, S., Sato, S., Wakita, M., Okumura, S., Nakano, S., Matsudaira, T., Matsumoto, T., Kawamoto, S., Yamamoto, M., Watanabe, T., Matsuura, Y., Takayama, K., Kobayashi, T., Okamoto, T., & *Hara, E.
SARS-CoV-2 infection triggers paracrine senescence and leads to a sustained senescence-associated inflammatory response.
Nature Aging, 2: 115-124 (2022)
Open access.
Okumura, S., Konishi, Y., Narukawa, M., Sugiura, Y., Yoshimoto, S., Arai, Y., Sato, S., Yoshida, Y., Tsuji, S., Uemura, U., 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.
Nature Commun., 12: 5674 doi: 10.1038/s41467-021-25965-x (2021).
This paper has been selected as one of the 2021 Top 25 Health Sciences Articles in Nature Communication!
Wakita, M., Takahashi, A., Sano, O., Loo, T. M., 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.
Nature Commun., 11:1935 doi: 10.1038/s41467-020-15719-6 (2020).
Takahashi, A., Loo, T. M., Okada, R., Kamachi, F., Watanabe, Y., Wakita, M., Watanabe, S., Kawamoto, S., Miyata, K., Barber, G. N., Ohtani, N. & *Hara, E.
Downregulation of cytoplasmic DNases is implicated in cytoplasmic DNA accumulation and SASP in senescent cells.
Nature Commun., 9: 1249 doi: 10.1038/s41467-081-03555-8 (2018).
*Okuma, A., Hanyu, A., Watanabe, S., & *Hara, E.
p16INK4a and p21Cip1/Waf1 promote tumour growth by enhancing myeloid-derived suppressor cells chemotaxis.
Nature Commun., 8: 2050 doi: 10.1038/s41467-017-02281-x (2017).
*Takasugi, M., Okada, R., Takahashi, A., Chen, D.V., Watanabe, S., & *Hara, E.
Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2.
Nature Commun., 8: 15728 doi: 10.1038/ncomms15728 (2017).
*Takahashi, A., Okada, R., Nagao, K., Kawamata, Y., Hanyu, A., Yoshimoto, S., Takasugi, M., Watanabe, S., Kanemaki, M.T., Obuse, C. & *Hara, E.
Exosomes maintain cellular homeostasis by excreting harmful DNA from cells.
Nature Commun., 8: 15287 doi: 10.1038/ncomms15287 (2017).
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 Commun., 6: 7035 doi: 10.1038/ncomms8035 (2015).
Imai, Y., Takahashi, A., Hanyu, 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 Rep., 7: 194-207 (2014) 
Yoshimoto, S., Loo, T.M., 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) 
(Selected for News & Views)
This work was featured in Science's 'Breakthrough of the Year 2013'
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.
Mol. Cell, 45: 123-131(2012) 
Yamakoshi, K., Takahashi, A., Hirota, F., Nakayama, R., Ishimaru, N., Kubo, Y., Mann, D.J., Ohmura, M., Hirao, A., Saya, H., Arase, S., Hayashi, Y., Nakao, K., Matsumoto, M., *Ohtani, N. & *Hara, E.
Real-time in vivo imaging of p16INK4a reveals cross-talk with p53.
J. Cell Biol., 186: 393-407 (2009)
*Ohtani, N., Imamura, Y., Yamakoshi, K., Hirota, F., Nakayama, R., Kubo, Y., Ishimaru, N., Takahashi, A., Hirao, A., Shimizu, T., Mann, D.J., Saya, H., Hayashi, Y., Arase, S., Matsumoto, M., Nakao, K. & *Hara, E.
Visualizing the dynamics of p21Waf1/Cip1 cyclin-dependent kinase inhibitor expression in living animals
Proc. Natl. Acad. Sci. USA, 104: 15034-15039 (2007)
Takahashi, A., Ohtani, N., Yamakoshi, K., Iida, S., Tahara, H.,Nakayama, K., Nakayama, K.I., Ide, T., Saya, H. & *Hara, E.
Mitogenic signalling and the p16INK4a-Rb pathway cooperate to enforce irreversible cellular senescence
Nature Cell Biol., 8: 1291-1297 (2006)
(Selected for News & Views)
Maehara, K., Yamakoshi, K., Ohtani, N., Kubo, Y., Takahashi, A., Arase, S., Jones, N. & *Hara, E.
Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53.
J. Cell Biol., 167: 553-560 (2005)
Ohtani, N., Brennan, P., Gaubatz, S., Sanij, E., Hertzong, P., Wolvetang, E., Ghysdael, J., Rowe, M. & *Hara, E.
Epstein-Barr virus LMP1 blocks p16INK4a-RB-pathway by promoting nuclear export of E2F4/5.
J. Cell Biol., 162: 173-183 (2003)
(Selected for Cover page)
Ohtani, N., Zebedee, Z., Huot, T.J.G., Stinson, J.A., Sugimoto, M., Ohashi, Y., Sharrrocks, A.D., Peters, G. & *Hara, E.
Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence.
Nature, 409: 1067-1070 (2001).
Sugimoto, M., Nakamura, T., Ohtani, N., Hampson, L., Hampson, I.N., Shimamoto, A., Furuichi, Y., Okumura, K., Niwa, S., Taya Y. & *Hara, E.
Regulation of CDK4 activity by a novel CDK4 binding protein, p34SEI-1.
Genes & Dev., 13: 3027-3033 (1999).


発表論文

*Corresponding author
*Endo, T., Kobayashi, K., Matsumura, T., Emori, C., Ozawa, M., Kawamoto, S., Okuzaki, D., Shimada, K., Miyata, H., Shimada, K., Kodani, M., Ishikawa-Yamauchi, Y., Motooka, D., Hara, E. & * Ikawa, M.
Multiple ageing effects on testicular/epididymal germ cells lead to decreased male fertility in mice.
Commun Biol. , doi: 10.1038/s42003-023-05685-22 (2024)
Abe, S., *Masuda, A., *Matsumoto, T., Inoue, J., Toyama, H., Sakai, A., Kobayashi, T., Tanaka, T., Tsujimae, M., Yamakawa, K., Gonda, M., Masuda, S., Uemura, H., Kohashi, S., Inomata, N., Nagao, K., Harada, Y., Miki, M., Irie, Y., Juri, N., Ko, T., Yokotani, Y., Oka, Y., Ota, S., Kanzawa, M., Itoh, T., Imai, T., Fukumoto, T., Hara, E. & Kodama Y.
Impact of intratumoral microbiome on tumor immunity and prognosis in human pancreatic ductal adenocarcinoma.
J Gastroenterol. , doi: 10.1007/s00535-023-02069-5 (2024)
Urano, E., Itoh, Y., Suzuki, T., Sasaki, T., Kishikawa, J.I., Akamatsu, K., Higuchi, Y., Sakai, Y., Okamura, T., Mitoma, S., Sugihara, F., Takada, A., Kimura, M., Nakao, S., Hirose, M., Sasaki, T., Koketsu, R., Tsuji, S., Yanagida, S., Shioda, T., Hara, E., Matoba, S., Matsuura, Y., Kanda, Y., Arase, H., Okada, M., Takagi, J., Kato, T., *Hoshino, A., *Yasutomi, Y., *Saito, A., & *Okamoto, T.
An inhaled ACE2 decoy confers protection against SARS-CoV-2 infection in preclinical models.
Science Transl. Med., doi: 10.1126/scitranslmed.adi2623. (2023).
*Matsudaira, T., Nakano, S., Konishi, Y., Kawamoto, S., Uemura, K., Kondo, T., Sakurai, K., Ozawa, T., Hikida, T., Komine, O., Yamanaka, K., Fujita, Y., Yamashita, T., Matsumoto, T., & *Hara, E.
Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype.
Commun Biol. , doi: 10.1038/s42003-023-05027-2 (2023)
Matsuura, T., Ueda, Y., Harada, Y., Hayashi, K., Horisaka, K., Yano, Y., So, S., Kido, M., Fukumoto, T., Kodama, Y., Hara, E., & *Matsumoto, T.
Histological diagnosis of polyploidy discriminates an aggressive subset of hepatocellular carcinomas with poor prognosis.
Br. J. Cancer. , doi: 10.1038/s41416-023-02408-6. (2023)
Yamagishi, R., Kamachi, F., Nakamura, M., Yamazaki, S., Kamiya, T., Takasugi, M., Cheng, Y., Nonaka, Y., Yukawa-Muto, Y., Thuy, L.T.T., 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 Immunol. doi:10.1126/sciimmunol.abl7209. (2022).
Sugawara, S., Okada, R., Loo, T.M., Tanaka, H., Miyata, K., Chiba, M., Kawasaki, H., Katoh, K., Kaji, S., Maezawa, Y., Yokote, K., Nakayama, M., Oshima, M., Nagao, K., Obuse, C., Nagayama, S., Takubo, K., Nakanishi, A., Kanemaki, M.T, Hara, E., & *Takahashi, A.
RNaseH2A downregulation drives inflammatory gene expression via genomic DNA fragmentation in senescent and cancer cells.
Commun Biol. , doi: 10.1038/s42003-022-04369-7. (2022).
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., doi: 10.1002/hep4.1954 (2022).
Yamamoto-Imoto, H., Minami, S., Shioda, T., Yamashita, Y., Sakai, S., Maeda, S., Yamamoto, T., Oki, S., Takashima, M., Yamamuro, T,, Yanagawa, K., Edahiro, R., Iwatani, M., So, M., Tokumura, A., Abe, T., Imamura, R., Nonomura, N., Okada, Y., Ayer, D.E., Ogawa, H., Hara, E., Takabatake, Y., Isaka, Y., Nakamura, S. & *Yoshimori, T.
Age-associated decline of MondoA drives cellular senescence through impaired autophagy and mitochondrial homeostasis.
Cell Rep., doi: 10.1016/j.celrep.2022.110444. (2022).
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., doi: 10.1002/cam4.4671. (2022).
Miyata, K., Imai, Y., Hori, S., Nishio, M., Loo, T.-M., Okada, R., yang, L., nakadai, T., maruyama, R., Fujii, R., Ueda, K., Jiang, L., Zheng, H., Toyokuni, S., Shirahige, K., Kojima, R., nakayama, M., Oshima, M., Nagayama, S., Seimiya, H., Saya, H., Hara, E. & *Takahashi, A.
Pericentromeric noncoding RNA changes DNA binding of CTCF and inflammatory gene expression in senescence and cancer.
Proc. Natl. Acad. Sci. USA, doi: 10.1073/pnas.2025647118.(2021).
Uchino, Y., Goto, Y., Konishi, Y., Tanabe, K., Toda, H., Wada, M., Kita, Y., Beppu, M., Mori, S., Hijioka, H., Otsuka, T., Natsugoe, S., Hara, E. & *Sugiura, T.
Colorectal Cancer Patients Have Four Specific Bacterial Species in Oral and Gut Microbiota in Common-A Metagenomic Comparison with Healthy Subjects.
Cancers, 13,3332. doi: 10.3390/cancers13133332.(2021).
Tanabe, Y., Kawamoto, S., Takaku, T., Morishita, S., Hirao, A., Komatsu, N., Hara, E., Mukaida, N. & *Baba, T.
Expansion of senescent megakaryocyte-lineage cells maintains CML cell leukemogenesis.
Blood Adv., 4:6175-6188 (2020).
Uni, M., Masamoto ,Y., Sato, T., Kamikubo, Y., Arai, S., Hara, E. & *Kurokawa, M.
Modeling ASXL1 mutation revealed impaired hematopoiesis caused by derepression of p16Ink4a through aberrant PRC1-mediated histone modification.
Leukemia, 33,191-204. doi: 10.1038/s41375-018-0198-6. (2019).
Tadokoro,Y., Hoshii,T., Yamazaki, S., Eto, K., Ema, H., Kobayashi, M., Ueno, M., Ohta, K., Arai, Y., Hara, E., Harada, K., Oshimam M., Oshima, H., Arai, F., Yoshimura, A., Nakauchi, H. & *Hirao, A.
Spred1 Safeguards Hematopoietic Homeostasis against Diet-Induced Systemic Stress.
Cell Stem Cell., 22:713-725(2018).
Loo, T.M., 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, M.M., 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 Discov., doi: 10.1158/2159-8290.CD-16-0932. (2017)
Takeuchi, S., Fukuda, K,, Arai,S., Nanjo, S., Yamada, T., Hara, E., Nishihara, H. & *Yano, S.
Organ-specific efficacy of HSP90 inhibitor in multiple-organ metastasis model of chemorefractory small cell lung cancer.
Int. J. Cancer, 138: 1281-1289. (2016)
*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 decline of submandibular gland function.
Aging Cell, doi: 10.1111/acel.12337.(2015)
Demaria, M., Ohtani, N., Youssef, S.A., Rodier, F., Toussaint, W., Mitchell, J.R., Laberge, R.M., Vijg, J., van Steeg, H., Dolle, M.E.T., Hoeijmakers, J.H.J., de Bruin, A., Hara, E. & *Campisi, J.
An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA
Dev. Cell, 31: 722-733 (2014)
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.
Mol Cell, 55: 73-84 (2014)
Kitajima,S., Miki, T., Takegami, Y., Kido, Y., Noda, M., Hara, E., Shamma, A. & *Takahashi,C.
Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) interferes with epidermal growth factor receptor (EGFR) signaling.
Oncogene, 70: 9381-9390. (2011)
Takeuchi, S., Takahashi, A., Motoi, N., Yoshimoto, S., Tajima, T., Yamakoshi, K., Hirao, A., Yanagi, S., Fukami, K., Ishikawa, Y., Sone, S., Hara, E., & Ohtani, N.
Intrinsic cooperation between p16INK4a and p21Waf1/Cip1 in the onset of cellular senescence and tumor suppression in vivo.
Cancer Res., 70: 9381-9390. (2010)
Inomata, K., Aoto, T., Binh, N.T., Okamoto, N., Tanimura, S., Wakayama, T., Iseki, S., Hara, E., Masunaga, T., Shimizu, H. & *Nishimura, E.K.
Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation.
Cell, 137: 1088-1099 (2009)
*Laman, H., Funes, J., Ye, H., Henderson, S., Galinanes-Garcia, L., Hara, E., Knowles, P., McDonald, N. & Boshoff, C.
Transforming activity of Fbxo7 is mediated specifically through regulation of cyclinD/cdk6.
EMBO J., 24: 3104-3116 (2005)
Sugimoto, M., Martin, N., Wilks, D.P., Tamai, K., Huot, T.J.G., Pantoja, C., Okumura, K., Serrano, M. & *Hara, E.
Activation of cyclin D1 kinase in murine fibroblasts lacking both p21Cip1 and p27Kip1.
Oncogene, 21: 8067-8074. (2002)
Stott, F.J., Bates, S.A., James, M., McConnell, B.B., Starborg, M., Brookes, S., Palmero, I., Ryan, K., Hara, E., Vousden, K.H. & *Peters, G.
The alternative product from the human CDKN2A locus, p14ARF, participates in a regulatory feedback loop with p53 and MDM2.
EMBO J., 17: 5001-5014. (1998)
Copyrights (c) 2015 Hara Laboratory. All Rights Reserved