Updated on 2024/10/22

写真a

 
MORODOMI YOSUKE
 
Organization
Faculty of Pharmaceutical Sciences Academic Researcher
Title
Academic Researcher
Contact information
メールアドレス
Tel
0926426337

Degree

  • Doctor of Medicine

Papers

  • Murine Nuclear Tyrosyl-tRNA Synthetase Deficiency Leads to Fat Storage Deficiency and Hearing Loss. International journal

    Julia A Jones, Jiadong Zhou, Jianjie Dong, Salvador Huitron-Resendiz, Ely Boussaty, Eduardo Chavez, Na Wei, Calin Dan Dumitru, Yosuke Morodomi, Taisuke Kanaji, Allen F Ryan, Rick Friedman, Tong Zhou, Sachiko Kanaji, Matthew Wortham, Simon Schenk, Amanda J Roberts, Xiang-Lei Yang

    The Journal of biological chemistry   300 ( 10 )   107756 - 107756   2024.10   ISSN:00219258 eISSN:1083-351X

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Journal of Biological Chemistry  

    Aminoacyl-tRNA synthetases (aaRS) are fundamental to the translation machinery with emerging roles in transcriptional regulation. Previous cellular studies have demonstrated tyrosyl-tRNA synthetase (YARS1 or TyrRS) as a stress response protein through its cytosol-nucleus translocation to maintain cellular homeostasis. Here, we established a mouse model with a disrupted TyrRS nuclear localization signal, revealing its systemic impact on metabolism. Nuclear TyrRS deficiency (YarsΔNLS) led to reduced lean mass, reflecting a mild developmental defect, and reduced fat mass, possibly due to increased energy expenditure. Consistently, YarsΔNLS mice exhibit improved insulin sensitivity and reduced insulin levels, yet maintain normoglycemia, indicative of enhanced insulin action. Notably, YarsΔNLS mice also develop progressive hearing loss. These findings underscore the crucial function of nuclear TyrRS in the maintenance of fat storage and hearing and suggest that aaRSs' regulatory roles can affect metabolic pathways and tissue-specific health. This work broadens our understanding of how protein synthesis interconnects metabolic regulation to ensure energy efficiency.

    DOI: 10.1016/j.jbc.2024.107756

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  • Nuclear translocation of an aminoacyl-tRNA synthetase may mediate a chronic "integrated stress response". International journal

    Julia A Jones, Na Wei, Haissi Cui, Yi Shi, Guangsen Fu, Navin Rauniyar, Ryan Shapiro, Yosuke Morodomi, Nadine Berenst, Calin Dan Dumitru, Sachiko Kanaji, John R Yates 3rd, Taisuke Kanaji, Xiang-Lei Yang

    Cell reports   42 ( 6 )   112632 - 112632   2023.6

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

    Various stress conditions are signaled through phosphorylation of translation initiation factor eukaryotic initiation factor 2α (eIF2α) to inhibit global translation while selectively activating transcription factor ATF4 to aid cell survival and recovery. However, this integrated stress response is acute and cannot resolve lasting stress. Here, we report that tyrosyl-tRNA synthetase (TyrRS), a member of the aminoacyl-tRNA synthetase family that responds to diverse stress conditions through cytosol-nucleus translocation to activate stress-response genes, also inhibits global translation. However, it occurs at a later stage than eIF2α/ATF4 and mammalian target of rapamycin (mTOR) responses. Excluding TyrRS from the nucleus over-activates translation and increases apoptosis in cells under prolonged oxidative stress. Nuclear TyrRS transcriptionally represses translation genes by recruiting TRIM28 and/or NuRD complex. We propose that TyrRS, possibly along with other family members, can sense a variety of stress signals through intrinsic properties of this enzyme and strategically located nuclear localization signal and integrate them by nucleus translocation to effect protective responses against chronic stress.

    DOI: 10.1016/j.celrep.2023.112632

  • 第5土曜特集 mRNAワクチンやゲノム編集で注目が集まる遺伝子治療 遺伝子治療技術を用いた疾患治療 肺癌に対する免疫細胞治療

    諸富 洋介, 原田 結, 米満 吉和

    医学のあゆみ   285 ( 5 )   440 - 445   2023.4   ISSN:00392359

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    Publisher:医歯薬出版  

    DOI: 10.32118/ayu28505440

    CiNii Research

  • Inflammatory platelet production stimulated by tyrosyl-tRNA synthetase mimicking viral infection. International journal

    Yosuke Morodomi, Sachiko Kanaji, Brian M Sullivan, Alessandro Zarpellon, Jennifer N Orje, Eric Won, Ryan Shapiro, Xiang-Lei Yang, Wolfram Ruf, Paul Schimmel, Zaverio M Ruggeri, Taisuke Kanaji

    Proceedings of the National Academy of Sciences of the United States of America   119 ( 48 )   e2212659119   2022.11

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

    Platelets play a role not only in hemostasis and thrombosis, but also in inflammation and innate immunity. We previously reported that an activated form of tyrosyl-tRNA synthetase (YRSACT) has an extratranslational activity that enhances megakaryopoiesis and platelet production in mice. Here, we report that YRSACT mimics inflammatory stress inducing a unique megakaryocyte (MK) population with stem cell (Sca1) and myeloid (F4/80) markers through a mechanism dependent on Toll-like receptor (TLR) activation and type I interferon (IFN-I) signaling. This mimicry of inflammatory stress by YRSACT was studied in mice infected by lymphocytic choriomeningitis virus (LCMV). Using Sca1/EGFP transgenic mice, we demonstrated that IFN-I induced by YRSACT or LCMV infection suppressed normal hematopoiesis while activating an alternative pathway of thrombopoiesis. Platelets of inflammatory origin (Sca1/EGFP+) were a relevant proportion of those circulating during recovery from thrombocytopenia. Analysis of these "inflammatory" MKs and platelets suggested their origin in myeloid/MK-biased hematopoietic stem cells (HSCs) that bypassed the classical MK-erythroid progenitor (MEP) pathway to replenish platelets and promote recovery from thrombocytopenia. Notably, inflammatory platelets displayed enhanced agonist-induced activation and procoagulant activities. Moreover, myeloid/MK-biased progenitors and MKs were mobilized from the bone marrow, as evidenced by their presence in the lung microvasculature within fibrin-containing microthrombi. Our results define the function of YRSACT in platelet generation and contribute to elucidate platelet alterations in number and function during viral infection.

    DOI: 10.1073/pnas.2212659119

  • Circulating immune cells with megakaryocyte signature in response to COVID-19 mRNA vaccination. International journal

    Taisuke Kanaji, Yosuke Morodomi, Sachiko Kanaji

    Thrombosis research   220   1 - 4   2022.10

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    Language:English  

    DOI: 10.1016/j.thromres.2022.10.003

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MISC

  • 【mRNAワクチンやゲノム編集で注目が集まる遺伝子治療】遺伝子治療技術を用いた疾患治療 肺癌に対する免疫細胞治療

    諸富 洋介, 原田 結, 米満 吉和

    医学のあゆみ   2023.4

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    Language:Japanese  

    肺癌は悪性度の高い疾患であり,わが国を含め世界各国の死因の上位を占めている.しかし,急速な科学技術の発展とともに分子標的薬などが開発され,治療法が一変してきている.そのなかでも,免疫チェックポイント阻害薬(ICI)が肺癌などの固形腫瘍にも有効であることが証明されて以来,悪性腫瘍も免疫の力によって制御できる可能性があることがわかってきた.本稿では,肺癌に対する免疫療法の現状を述べるとともに,特に近年注目を集めているナチュラルキラー細胞(NK細胞)を用いた細胞治療について概説する.(著者抄録)

  • 腹膜播種の全容解明 Sp1によるCXCR4/CXCL12シグナル活性化と細胞外マトリクスを介したスフェア形成

    原田 結, 笠木 勇太, 諸富 洋介, 米満 吉和

    日本癌学会総会記事   2016.10

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    Language:English  

  • 有瘻性膿胸に対する持続洗浄を併用した閉鎖式陰圧療法

    諸富 洋介, 岡本 龍郎, 山口 正史, 井上 要二郎, 高田 和樹, 桂 正和, 鈴木 雄三, 藤下 卓才, 北原 大和, 田川 哲三, 竹之山 光広, 一瀬 幸人, 前原 喜彦

    日本呼吸器外科学会雑誌   2015.4

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    Language:Japanese  

  • 栄養・感染症・緩和 悪性胸水に対するドレナージおよび胸膜癒着術の原発巣別検討

    諸富 洋介, 岡本 龍郎, 高田 和樹, 桂 正和, 鈴木 雄三, 藤下 卓才, 北原 大和, 島松 晋一郎, 田川 哲三, 徳永 えり子, 沖 英次, 調 憲, 前原 喜彦

    日本外科学会定期学術集会抄録集   2015.4

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    Language:Japanese  

  • 悪性胸膜中皮腫における線溶系分子の発現と臨床病理学的因子に関する検討

    諸富 洋介, 岡本 龍郎, 高田 和樹, 桂 正和, 鈴木 雄三, 藤下 卓才, 北原 大和, 島松 晋一郎, 田川 哲三, 岡野 慎士, 田口 健一, 竹之山 光広, 一瀬 幸人, 前原 喜彦

    肺癌   2014.10

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    Language:Japanese  

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Research Projects

  • 血小板をベクターとして用いる癌に対する革新的ドラッグデリバリーシステムの開発

    Grant number:23H02769  2023 - 2025

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant type:Scientific research funding

  • 血小板をベクターとして用いる癌に対する革新的ドラッグデリバリーシステムの開発

    Grant number:23H02769  2023 - 2025

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • がん幹細胞化に関与するSphere形成メカニズムを標的とした革新的治療開発

    Grant number:15H05792  2015 - 2019

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant type:Scientific research funding

  • 肺扁平上皮癌における喫煙量別比較に基づいた新たなドライバー遺伝子変異の同定

    Grant number:15K10263  2015 - 2017

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant type:Scientific research funding

  • 悪性胸膜中皮腫の微小環境の特性を標的とした新規治療法の開発

    Grant number:25861255  2013 - 2015

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant type:Scientific research funding

Travel Abroad

  • 2015.11 - 2022.7

    Staying countory name 1:United States   Staying institution name 1:Scripps Research Institute