Updated on 2022/09/14

写真a

 
MIYAKE Yasuyuki
 
Organization
Graduate School of Medicine Center for Research of Laboratory Animals and Medical Research Engineering Division for Advanced Medical Research Assistant Professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine Department of Medicine
Title
Assistant Professor
Contact information
メールアドレス
External link

Degree 3

  1. Ph.D. ( 2006.3   Osaka University ) 

  2. Master(Integrated Biosciences) ( 2002.3   The University of Tokyo ) 

  3. BSc ( 2000.3   Shinshu University ) 

Research Interests 6

  1. RNA virus

  2. Influenzavirus

  3. vRNPs

  4. ubiquitin

  5. HDAC6

  6. molecular structure

Research Areas 2

  1. Life Science / Molecular biology  / Molecular Biology

  2. Life Science / Virology  / Virology

Current Research Project and SDGs 1

  1. ウイルス感染における宿主因子の動態と分子機能の解明

Research History 7

  1. Nagoya University   Graduate School of Medicine   Assistant Professor

    2020.4

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    Country:Japan

  2. University of Bristol   School of Cellular and Molecular Medicine   Researcher

    2018.5 - 2020.3

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    Country:United Kingdom

  3. Nagoya University   Graduate School of Medicine   JSPS Research Fellow

    2018.4 - 2020.3

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    Country:Japan

  4. Shinshu University   Researcher

    2016.4 - 2018.3

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    Country:Japan

  5. Friedrich Miescher Institute for Biomedical Research   Epigenetics group   Researcher

    2010.3 - 2015.12

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    Country:Switzerland

  6. Kyoto University   Graduate School of Biostudies   Researcher

    2006.4 - 2010.3

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    Country:Japan

  7. RIKEN   Laboratory of Cellular Physiology   Student Trainee

    2002.4 - 2006.3

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    Country:Japan

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Education 2

  1. Osaka University   Graduate School, Division of Medical Sciences

    - 2006.3

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    Country: Japan

  2. The University of Tokyo

    - 2002.3

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    Country: Japan

Professional Memberships 3

  1. 日本分子生物学会

    2000.12

  2. 日本ウイルス学会

    2020.9

  3. 日本細胞生物学会

    2022.3

Awards 2

  1. CMM Awayday Best Poster Prize

    2019.1   University of Bristol   Influenza virus uses transportin 1 for vRNP debundling during cell entry

    Miyake Yasuyuki

  2. Pfizer Forschungspreis (Infektiologie, Rheumatologie und Immunologie)

    2016.1   Pfizer  

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    Award type:International academic award (Japan or overseas)  Country:Switzerland

 

Papers 10

  1. Influenza virus uses transportin 1 for vRNP debundling during cell entry Reviewed International coauthorship

    Miyake Y, Keusch JJ, Decamps L, Ho-Xuan H, Iketani S, Gut H, Kutay U, Helenius A, Yamauchi Y

    Nature Microbiology   Vol. 4 ( 4 ) page: 578 - 586   2019.4

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41564-018-0332-2

  2. Structural insights into HDAC6 tubulin deacetylation and its selective inhibition Reviewed

    Miyake Y, Keusch JJ, Wang L, Saito M, Hess D, Wang X, Melancon BJ, Helquist P, Gut H, Matthias P

    Nature Chemical Biology   Vol. 12 ( 9 ) page: 748 - 754   2016.9

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nchembio.2140

  3. Influenza A virus uses the aggresome processing machinery for host cell entry Reviewed

    Banerjee I, Miyake Y, Nobs SP, Schneider C, Horvath P, Kopf M, Matthias P, Helenius A, Yamauchi Y

    Science   Vol. 346 ( 6208 ) page: 473 - 477   2014.10

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1126/science.1257037

  4. RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-stranded DNA and protects telomeres independently of the Pot1 pathway Reviewed

    Miyake Y, Nakamura M, Nabetani A, Shimamura S, Tamura M, Yonehara S, Saito M, Ishikawa F

    Molecular cell   Vol. 36 ( 2 ) page: 193 - 206   2009.10

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.molcel.2009.08.009

  5. Biochemistry of influenza virus entry Reviewed

    Miyake Yasuyuki, Yamauchi Yohei

      Vol. 94 ( 3 ) page: 427 - 432   2022.6

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.14952/seikagaku.2022.940427

    CiNii Research

  6. Disrupting the HDAC6-ubiquitin interaction impairs infection by influenza and Zika virus and cellular stress pathways Reviewed

    Wang Longlong, Moreira Etori Aguiar, Kempf Georg, Miyake Yasuyuki, Esteves Blandina I. Oliveira, Fahmi Amal, Schaefer Jonas V, Dreier Birgit, Yamauchi Yohei, Alves Marco P., Plueckthun Andreas, Matthias Patrick

    CELL REPORTS   Vol. 39 ( 4 ) page: 110736   2022.4

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Cell Reports  

    The deacetylase HDAC6 has tandem catalytic domains and a zinc finger domain (ZnF) binding ubiquitin (Ub). While the catalytic domain has an antiviral effect, the ZnF facilitates influenza A virus (IAV) infection and cellular stress responses. By recruiting Ub via the ZnF, HDAC6 promotes the formation of aggresomes and stress granules (SGs), dynamic structures associated with pathologies such as neurodegeneration. IAV subverts the aggresome/HDAC6 pathway to facilitate capsid uncoating during early infection. To target this pathway, we generate designed ankyrin repeat proteins (DARPins) binding the ZnF; one of these prevents interaction with Ub in vitro and in cells. Crystallographic analysis shows that it blocks the ZnF pocket where Ub engages. Conditional expression of this DARPin reversibly impairs infection by IAV and Zika virus; moreover, SGs and aggresomes are downregulated. These results validate the HDAC6 ZnF as an attractive target for drug discovery.

    DOI: 10.1016/j.celrep.2022.110736

    Web of Science

    Scopus

    PubMed

  7. A STING inhibitor suppresses EBV-induced B cell transformation and lymphomagenesis Reviewed

    Miyagi Shouhei, Watanabe Takahiro, Hara Yuya, Arata Masataka, Uddin Md. Kamal, Mantoku Keisuke, Sago Ken, Yanagi Yusuke, Suzuki Takeshi, Masud H. M. Abdullah Al, Kawada Jun-ichi, Nakamura Shigeo, Miyake Yasuyuki, Sato Yoshitaka, Murata Takayuki, Kimura Hiroshi

    CANCER SCIENCE   Vol. 112 ( 12 ) page: 5088 - 5099   2021.12

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Cancer Science  

    Epstein-Barr virus-associated lymphoproliferative disease (EBV-LPD) is frequently fatal. Innate immunity plays a key role in protecting against pathogens and cancers. The stimulator of interferon genes (STING) is regarded as a key adaptor protein allowing DNA sensors recognizing exogenous cytosolic DNA to activate the type I interferon signaling cascade. In terms of EBV tumorigenicity, the role of STING remains elusive. Here we showed that treatment with the STING inhibitor, C-176, suppressed EBV-induced transformation in peripheral blood mononuclear cells. In an EBV-LPD mouse model, C-176 treatment also inhibited tumor formation and prolonged survival. Treatment with B cells alone did not affect EBV transformation, but suppression of EBV-induced transformation was observed in the presence of T cells. Even without direct B cell-T cell contact in a transwell system, the inhibitor reduced the transformation activity, indicating that intercellular communication by humoral factors was critical to prevent EBV-induced transformation. These findings suggest that inhibition of STING signaling pathway with C-176 could be a new therapeutic target of EBV-LPD.

    DOI: 10.1111/cas.15152

    Web of Science

    Scopus

    PubMed

  8. Acetylation site specificities of lysine deacetylase inhibitors in human cells Reviewed International coauthorship

    Schölz C, Weinert BT, Wagner SA, Beli P, Miyake Y, Qi J, Jensen LJ, Streicher W, McCarthy AR, Westwood NJ, Lain S, Cox J, Matthias P, Mann M, Bradner JE, Choudhary C

    Nature biotechnology   Vol. 33 ( 4 ) page: 415 - 423   2015.4

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nbt.3130

  9. Aberrant DNA polymerase alpha is excluded from the nucleus by defective import and degradation in the nucleus Reviewed

    Eichinger CS, Mizuno T, Mizuno K, Miyake Y, Yanagi K, Imamoto N, Hanaoka F

    The Journal of Biological Chemistry   Vol. 284 ( 44 ) page: 30604 - 30614   2009.10

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1074/jbc.M109.024760

  10. Novel splicing variant of mouse Orc1 is deficient in nuclear translocation and resistant for proteasome-mediated degradation Reviewed

    Miyake Y, Mizuno T, Yanagi K, Hanaoka F

    The Journal of Biological Chemistry   Vol. 280 ( 13 ) page: 12643 - 12652   2005.4

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1074/jbc.M413280200

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Books 2

  1. Molecular function of host factors involved in cellular entry of influenza A virus

    Yasuyuki Miyake( Role: Sole author ,  Topics from special edition)

    the New Science Co., Ltd.  2022.5 

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    Language:Japanese Book type:Textbook, survey, introduction

  2. Purification of Unanchored Polyubiquitin Chains from Influenza Virions

    Miyake Yasuyuki, Matthias Patrick, Yamauchi Yohei( Role: Contributor ,  Chapter 16)

    Humana Press  2018  ( ISBN:978-1-4939-8677-4

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    Responsible for pages:329-342   Language:English Book type:Scholarly book

    DOI: 10.1007/978-1-4939-8678-1_16

MISC 1

  1. ヒストン脱アセチル化酵素HDAC6の結晶構造から明らかにされたチューブリンに対する特異性および選択的な阻害剤との結合 Invited International coauthorship

    三宅康之 , パトリック マティアス

    ライフサイエンス新着論文レビュー     2016.8

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    Authorship:Lead author   Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

    DOI: 10.7875/first.author.2016.083

Presentations 3

  1. ENDOSOMAL DEUBIQUITINASE USP7 PROMOTES INFLUENZA VIRUS UNCOATING International coauthorship International conference

    Yasuyuki Miyake

    Negative Strand Virus meeting 2022  2022.6.13  NSV meeting organizing commitee

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    Event date: 2022.6

    Language:English   Presentation type:Oral presentation (general)  

    Venue:Portugal   Country:Portugal  

  2. Molecular mechanism(s) for cellular entry of RNA viruses Invited

    Yasuyuki Miyake

    Premium Lecture  2021.11.18 

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    Event date: 2021.11

    Language:English   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    Country:Japan  

  3. Molecular function of USP7 protein in cellular entry of influenza virus International coauthorship

    Alina Rozanova, Yasuyuki Miyake, and Yohei Yamauchi

    43th BMSJ 2020  2020.12.3 

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    Event date: 2020.12

    Language:English   Presentation type:Poster presentation  

    Venue:online   Country:Japan  

Research Project for Joint Research, Competitive Funding, etc. 2

  1. ウイルス感染における宿主因子の動態と分子機能の解明

    2021.4 - 2024.3

    科学技術振興機構  創発的研究支援事業 

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    Grant type:Competitive

  2. The HDAC6/USP7 axis in enveloped RNA virus infection

    2019.12 - 2023.3

    Yasuyuki Miyake

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    Grant type:Competitive

KAKENHI (Grants-in-Aid for Scientific Research) 2

  1. インフルエンザウイルスとヒト免疫不全症候群ウイルスの脱殻分子メカニズムの解明

    2020.4 - 2023.3

    科学研究費補助金  基盤研究(C)

    三宅康之

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    Authorship:Principal investigator 

     ヒトの感染症を引き起こすインフルエンザ、コロナ、エボラ、デング、ジカといった脂質二重膜に包まれたエンベロープRNAウイルスは、細胞内にエンドサイトーシスと呼ばれる食作用で取り込まれる。その後エンドソーム内部の環境が変化することでエンドソーム膜に融合し、ウイルスゲノムが細胞質内へ放出される。ウイルスの細胞内への侵入の素過程における宿主因子の機能の理解は、RNAウイルスの細胞内侵入のメカニズムだけでなく、将来的に宿主因子を標的とした新たな抗ウイルス薬の開発につながることが期待される。そこで、宿主因子とウイルス殻タンパク質の複合体を生化学的に精製し、その分子構造と相互作用メカニズムを明らかにする。

  2. ユビキチンを利用したインフルエンザウイルス脱殻の分子機構解明

    2018.4 - 2020.3

    科学研究費補助金 

    三宅康之

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    Authorship:Principal investigator 

     ヒストン脱アセチル化酵素HDAC6は、インフルエンザウイルスが細胞内に侵入する際のウイルスの脱殻において重要な役割を果たしている。後期エンドソームにおいてウイルス内部に存在するユビキチンを細胞質側に提示することでHDAC6がリクルートされ、HDAC6とダイニン・ミオシンモーター及び微小管・アクチンフィラメントなどとの分子間相互作用によりウイルスの脱殻が促される。しかし特定のユビキチン鎖がシグナルとなって、HDAC6をリクルートしているのかは不明である。
     in vitroの実験において、インフルエンザウイルスを後期エンドソームを模倣した低pH条件のバッファーに晒し、HDAC6のユビキチン結合ドメインとの相互作用を調べた結果、ポリユビキチン鎖がより多く結合していることを明らかにしてきた。現在、この後期エンドソームでの低pHによるプライミングがウイルスのユビキチンに与える影響を含め、ウイルスがHDAC6に認識されやすい特定のユビキチン鎖を持つのか生化学的に解析している。またHDAC6へのユビキチン結合を阻害するNanobodyとHDAC6との複合体の相互作用解析を通じて、抗インフルエンザウイルス薬の基盤を構築する。

Industrial property rights 1

  1. New treatment against influenza virus

    Banerjee I , Helenius A , Matthias P , Miyake Y , Yamauchi Y

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    Application no:WO2015189816 A1  Date applied:2015

 

Teaching Experience (On-campus) 6

  1. Virology 3

    2022

  2. Molecular Pathology

    2022

  3. Microorganisms and Human

    2021

  4. Molecular Pathology

    2021

  5. 病理病態学

    2020

  6. 生体と微生物 ウイルス学総論3

    2020

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Teaching Experience (Off-campus) 1

  1. ウイルス学

    2022.1 Nagoya City University)

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    Level:Undergraduate (specialized)  Country:Japan