Researcher Database

Yamada Taisho
Institute for Genetic Medicine Molecular Pathogenesis
Assistant Professor

Researcher Profile and Settings


  • Institute for Genetic Medicine Molecular Pathogenesis

Job Title

  • Assistant Professor

J-Global ID

Research Interests

  • シグナル伝達   自然免疫   

Research Areas

  • Life sciences / Immunology

Academic & Professional Experience

  • 2016/04 - Today Hokkaido University Institute for Genetic Medicine


  • 2012/04 - 2016/03  北海道大学大学院
  • 2010/04 - 2012/03  北海道大学大学院
  • 2006/04 - 2010/03  University of Tsukuba

Research Activities

Published Papers

  • Sunanda Baidya, Yoko Nishimoto, Seiichi Sato, Yasuhiro Shimada, Nozomi Sakurai, Hirotaka Nonaka, Koki Noguchi, Mizuki Kido, Satoshi Tadano, Kozo Ishikawa, Kai Li, Aoi Okubo, Taisho Yamada, Yasuko Orba, Michihito Sasaki, Hirofumi Sawa, Hiroko Miyamoto, Ayato Takada, Takashi Nakamura, Akinori Takaoka
    Viruses 13 (9) 1674 - 1674 2021/08/24 [Refereed]
    The interaction of viral nucleic acid with protein factors is a crucial process for initiating viral polymerase-mediated viral genome replication while activating pattern recognition receptor (PRR)-mediated innate immune responses. It has previously been reported that a hydrolysate of Ge-132, 3-(trihydroxygermyl) propanoic acid (THGP), shows a modulatory effect on microbial infections, inflammation, and immune responses. However, the detailed mechanism by which THGP can modify these processes during viral infections remained unknown. Here, we show that THGP can specifically downregulate type I interferon (IFN) production in response to stimulation with a cytosolic RNA sensor RIG-I ligand 5′-triphosphate RNA (3pRNA) but not double-stranded RNA, DNA, or lipopolysaccharide. Consistently, treatment with THGP resulted in the dose-dependent suppression of type I IFN induction upon infections with influenza virus (IAV) and vesicular stomatitis virus, which are known to be mainly sensed by RIG-I. Mechanistically, THGP directly binds to the 5′-triphosphate moiety of viral RNA and competes with RIG-I-mediated recognition. Furthermore, we found that THGP can directly counteract the replication of IAV but not EMCV (encephalitismyocarditis virus), by inhibiting the interaction of viral polymerase with RNA genome. Finally, IAV RNA levels were significantly reduced in the lung tissues of THGP-treated mice when compared with untreated mice. These results suggest a possible therapeutic implication of THGP and show direct antiviral action, together with the suppressive activity of innate inflammation.
  • Taisho Yamada, Seiichi Sato, Yuki Sotoyama, Yasuko Orba, Hirofumi Sawa, Hajime Yamauchi, Michihito Sasaki, Akinori Takaoka
    Nature Immunology 22 (7) 820 - 828 1529-2908 2021/07 [Refereed]
    Efficient immune responses against viral infection are determined by sufficient activation of nucleic acid sensor-mediated innate immunity1,2. Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains an ongoing global pandemic. It is an urgent challenge to clarify the innate recognition mechanism to control this virus. Here we show that retinoic acid-inducible gene-I (RIG-I) sufficiently restrains SARS-CoV-2 replication in human lung cells in a type I/III interferon (IFN)-independent manner. RIG-I recognizes the 3' untranslated region of the SARS-CoV-2 RNA genome via the helicase domains, but not the C-terminal domain. This new mode of RIG-I recognition does not stimulate its ATPase, thereby aborting the activation of the conventional mitochondrial antiviral-signaling protein-dependent pathways, which is in accordance with lack of cytokine induction. Nevertheless, the interaction of RIG-I with the viral genome directly abrogates viral RNA-dependent RNA polymerase mediation of the first step of replication. Consistently, genetic ablation of RIG-I allows lung cells to produce viral particles that expressed the viral spike protein. By contrast, the anti-SARS-CoV-2 activity was restored by all-trans retinoic acid treatment through upregulation of RIG-I protein expression in primary lung cells derived from patients with chronic obstructive pulmonary disease. Thus, our findings demonstrate the distinctive role of RIG-I as a restraining factor in the early phase of SARS-CoV-2 infection in human lung cells.
  • Akinori Takaoka, Taisho Yamada
    International Immunology 15 dxz034  2019/04 [Refereed][Not invited]
  • In vitro Treatment of Mouse and Human Cells with Endogenous Ligands for Activation of the Aryl Hydrocarbon Receptor.
    Taisho Yamada, Akinori Takaoka
    Bio-protocol 7 e2097  2017 [Refereed][Not invited]
  • FICZ Exposure and Viral Infection in Mice.
    Taisho Yamada, Akinori Takaoka
    Bio-protocol 7 e2096  2017 [Refereed][Not invited]
  • Taisho Yamada, Hiromasa Horimoto, Takeshi Kameyama, Sumio Hayakawa, Hiroaki Yamato, Masayoshi Dazai, Ayato Takada, Hiroshi Kida, Debbie Bott, Angela C. Zhou, David Hutin, Tania H. Watts, Masahiro Asaka, Jason Matthews, Akinori Takaoka
    Nature Immunology 17 (6) 687 - + 1529-2908 2016/06 [Refereed][Not invited]
    Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxic activity of many environmental xenobiotics. However, its role in innate immune responses during viral infection is not fully understood. Here we demonstrate that constitutive AHR signaling negatively regulates the type I interferon (IFN-I) response during infection with various types of virus. Virus-induced IFN-beta production was enhanced in AHR-deficient cells and mice and resulted in restricted viral replication. We found that AHR upregulates expression of the ADP-ribosylase TIPARP, which in turn causes downregulation of the IFN-I response. Mechanistically, TIPARP interacted with the kinase TBK1 and suppressed its activity by ADP-ribosylation. Thus, this study reveals the physiological importance of endogenous activation of AHR signaling in shaping the IFN-I-mediated innate response and, further, suggests that the AHR-TIPARP axis is a potential therapeutic target for enhancing antiviral responses.
  • Sumio Hayakawa, Souichi Shiratori, Hiroaki Yamato, Takeshi Kameyama, Chihiro Kitatsuji, Fumi Kashigi, Showhey Goto, Shoichiro Kameoka, Daisuke Fujikura, Taisho Yamada, Tatsuaki Mizutani, Mika Kazumata, Maiko Sato, Junji Tanaka, Masahiro Asaka, Yusuke Ohba, Tadaaki Miyazaki, Masahiro Imamura, Akinori Takaoka
    Nature Immunology 12 (1) 37 - U56 1529-2908 2011/01 [Refereed][Not invited]
    The poly(ADP-ribose) polymerases (PARPs) participate in many biological and pathological processes. Here we report that the PARP-13 shorter isoform (ZAPS), rather than the full-length protein (ZAP), was selectively induced by 5'-triphosphate-modified RNA (3pRNA) and functioned as a potent stimulator of interferon responses in human cells mediated by the RNA helicase RIG-I. ZAPS associated with RIG-I to promote the oligomerization and ATPase activity of RIG-I, which led to robust activation of IRF3 and NF-kappa B transcription factors. Disruption of the gene encoding ZAPS resulted in impaired induction of interferon-alpha (IFN-alpha), IFN-beta and other cytokines after viral infection. These results indicate that ZAPS is a key regulator of RIG-I signaling during the innate antiviral immune response, which suggests its possible use as a therapeutic target for viral control.


  • SARS-CoV-2に対するRIG-Iの新たな感染防御機能
    山田大翔, 石姝珣, 髙岡晃教  臨床免疫・アレルギー科  77-  (1)  92  -99  2022
  • Akinori Takaoka, Seiichi Sato, Taisho Yamada  Handbook of Hormones  435  -435  2021
  • 日本インターフェロン・サイトカイン学会奨励賞を受賞して
    山田大翔  JSICRニュースレター  48-  2021
  • SARS-CoV-2に対する自然免疫系RNAセンサーの新たな抗ウイルス機能
    山田大翔, 髙岡晃教  実験医学  40-  (1)  78  -81  2021
  • 自然免疫センサーを介する抗SARS-CoV-2 intrinsic immunity
    髙岡晃教, 山田大翔  日本免疫学会 JSI Newsletter  30-  (1)  5  2021
  • ヒト肺細胞でのSARS-CoV-2感染に対するintrinsic immunityのメカニズム
    山田大翔, 佐藤精一, 外山雄貴, 大場靖子, 澤洋文, 山内肇, 佐々木道仁, 髙岡晃教  北海道医学雑誌  96-  (2)  72  2021
  • Tumor necrosis factor alpha
    Taisho Yamada, Akinori Takaoka  Handbook of Hormones 2nd Edition  Chapter 39b  2021
  • 内在性のリガンドによる芳香族炭化水素受容体(AHR)の恒常的な活性化はウイルス感染に対するI型インターフェロン応答を抑制する.
    山田 大翔  北海道医学雑誌  92-  74  -76  2017  [Not refereed][Not invited]
  • 山田大翔, 髙岡晃教  医学のあゆみ  260-  (10)  913  -915  2017  [Not refereed][Not invited]
  • 内在性のリガンドによる芳香族炭化水素受容体(AHR)の恒常的な活性化はウイルス感染に対するI型インターフェロン応答を抑制する.
    山田大翔, 堀本啓大, 亀山武志, 早川清雄, 大和弘明, 太宰昌佳, 高田礼人, 喜田宏, Debbie Bott・Angela C. Zhou, David Huntin, Tania H. Watts, 浅香正博, Jason Matthews, 髙岡晃教  北海道医学雑誌  91-  80  2016  [Not refereed][Not invited]
  • 内因性のリガンドによるAh受容体の恒常的な活性化はウイルスの感染によるI型インターフェロンの産生の誘導を抑制する
    山田大翔, 髙岡晃教  ライフサイエンス新着論文レビュー(FIRST AUTHOR’S (Web))  2016  [Not refereed][Not invited]
  • Yamada T, Takaoka A  Nihon rinsho. Japanese journal of clinical medicine  70 Suppl 8-  225  -230  2012/11  [Not refereed][Not invited]
  • 白鳥 聡一, 早川 清雄, 大和 弘明, 亀山 武志, 北辻 千展, 樫木 芙美, 後藤 翔平, 亀岡 章一郎, 藤倉 大輔, 山田 大翔, 水谷 龍明, 数馬田 美香, 佐藤 麻衣子, 田中 淳司, 浅香 正博, 大場 雄介, 宮崎 忠昭, 今村 雅寛, 高岡 晃教  北海道醫學雜誌 = Acta medica Hokkaidonensia  87-  (4)  194  -194  2012/08/01  [Not refereed][Not invited]
  • 髙岡晃教, 山田大翔, 林真寛  生物の科学 遺伝  Vol. 65-  (No.6)  80  -91  2011  [Not refereed][Not invited]

Awards & Honors

  • 2021/05 第17回日本インターフェロン・サイトカイン学会奨励賞
    受賞者: 山田 大翔
  • 2017/03 北海道医学会 研究奨励賞
    受賞者: 山田 大翔
  • 2017/02 北海道大学医学部同窓会 フラテ研究奨励賞
    受賞者: 山田 大翔
  • 2016/08 ICI-FIMSA Travel Awards (Austraria)
    受賞者: 山田 大翔

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