研究者データベース

應田 涼太(オウダ リヨウタ)
医学研究院 病理系部門 微生物学免疫学分野
助教

基本情報

所属

  • 医学研究院 病理系部門 微生物学免疫学分野

職名

  • 助教

学位

  • 生命科学博士(京都大学)

科研費研究者番号

  • 90817321

J-Global ID

研究キーワード

  • 自然免疫   

研究分野

  • ライフサイエンス / 免疫学

職歴

  • 2018年07月 - 現在 北海道大学 医学研究院 助教
  • 2017年04月 - 2018年06月 京都大学 ウイルス・再生医科学研究所 研究員
  • 2014年04月 - 2017年03月 米国立衛生研究所 研究員
  • 2013年04月 - 2014年03月 京都大学 ウイルス研究所 日本学術振興会 特別研究員

学歴

  • 2008年04月 - 2013年03月   京都大学 大学院   生命科学研究科

研究活動情報

論文

  • Ji-Seung Yoo, Michihito Sasaki, Steven X. Cho, Yusuke Kasuga, Baohui Zhu, Ryota Ouda, Yasuko Orba, Paul de Figueiredo, Hirofumi Sawa, Koichi S. Kobayashi
    Nature Communications 12 1 2021年12月 
    AbstractThe MHC class I-mediated antigen presentation pathway plays a critical role in antiviral immunity. Here we show that the MHC class I pathway is targeted by SARS-CoV-2. Analysis of the gene expression profile from COVID-19 patients as well as SARS-CoV-2 infected epithelial cell lines reveals that the induction of the MHC class I pathway is inhibited by SARS-CoV-2 infection. We show that NLRC5, an MHC class I transactivator, is suppressed both transcriptionally and functionally by the SARS-CoV-2 ORF6 protein, providing a mechanistic link. SARS-CoV-2 ORF6 hampers type II interferon-mediated STAT1 signaling, resulting in diminished upregulation of NLRC5 and IRF1 gene expression. Moreover, SARS-CoV-2 ORF6 inhibits NLRC5 function via blocking karyopherin complex-dependent nuclear import of NLRC5. Collectively, our study uncovers an immune evasion mechanism of SARS-CoV-2 that targets the function of key MHC class I transcriptional regulators, STAT1-IRF1-NLRC5.
  • Ruibo Li, Ryota Ouda, Chihiro Kimura, Ryo Narita, Hiroshi Nishimura, Takashi Fujita, Takashi Watanabe
    ACS Sustainable Chemistry & Engineering 2021年06月15日
  • Steven X Cho, Saptha Vijayan, Ji-Seung Yoo, Toshiyuki Watanabe, Ryota Ouda, Ning An, Koichi S Kobayashi
    Immunology 162 3 252 - 261 2021年03月 
    The presentation of antigenic peptides by major histocompatibility complex (MHC) class I and class II molecules is crucial for activation of the adaptive immune system. The nucleotide-binding domain and leucine-rich repeat receptor family members CIITA and NLRC5 function as the major transcriptional activators of MHC class II and class I gene expression, respectively. Since the identification of NLRC5 as the master regulator of MHC class I and class-I-related genes, there have been major advances in understanding the function of NLRC5 in infectious diseases and cancer. Here, we discuss the biological significance and mechanism of NLRC5-dependent MHC class I expression.
  • Chihiro Kimura, Ruibo Li, Ryota Ouda, Hiroshi Nishimura, Takashi Fujita, Takashi Watanabe
    ChemSusChem 2020年05月12日 [査読有り][通常論文]
  • Takeuchi F, Ikeda S, Tsukamoto Y, Iwasawa Y, Qihao C, Otakaki Y, Ryota O, Yao WL, Narita R, Makoto H, Watashi K, Wakita T, Takeuchi K, Chayama K, Kogure A, Kato H, Fujita T
    PloS one 14 2 e0212233  2019年 [査読有り][通常論文]
     
    Currently, there is no available therapy to eradicate hepatitis B virus (HBV) in chronically infected individuals. This is due to the difficulty in eliminating viral covalently closed circular (ccc) DNA, which is central to the gene expression and replication of HBV. We developed an assay system for nuclear circular DNA using an integration-deficient lentiviral vector. This vector produced non-integrated circular DNA in nuclei of infected cells. We engineered this vector to encode firefly luciferase to monitor the lentiviral episome DNA. We screened 3,840 chemicals by this assay for luciferase-reducing activity and identified dicumarol, which is known to have anticoagulation activity. We confirmed that dicumarol reduced lentiviral episome DNA. Furthermore, dicumarol inhibited HBV replication in cell culture using NTCP-expressing HepG2 and primary human hepatocytes. Dicumarol reduced intracellular HBV RNA, DNA, supernatant HBV antigens and DNA. We also found that dicumarol reduced the cccDNA level in HBV infected cells, but did not affect HBV adsorption/entry. This is a novel assay system for screening inhibitors targeting nuclear cccDNA and is useful for finding new antiviral substances for HBV.
  • Takashi Watanabe, Ruibo Li, Chihiro Kimura, Ryota Ouda, Ryo Narita, Hiroshi Nishimura, Takashi Fujita
    Sustainable humanosphere : bulletin of Research Institute for Sustainable Humanosphere Kyoto University 14 2 - 2 2018年09月10日 [査読無し][通常論文]
  • Kamada R, Yang W, Zhang Y, Patel MC, Yang Y, Ouda R, Dey A, Wakabayashi Y, Sakaguchi K, Fujita T, Tamura T, Zhu J, Ozato K
    Proceedings of the National Academy of Sciences of the United States of America 115 39 E9162-E9171  2018年09月 [査読有り][通常論文]
     
    Epigenetic memory for signal-dependent transcription has remained elusive. So far, the concept of epigenetic memory has been largely limited to cell-autonomous, preprogrammed processes such as development and metabolism. Here we show that IFNβ stimulation creates transcriptional memory in fibroblasts, conferring faster and greater transcription upon restimulation. The memory was inherited through multiple cell divisions and led to improved antiviral protection. Of ∼2,000 IFNβ-stimulated genes (ISGs), about half exhibited memory, which we define as memory ISGs. The rest, designated nonmemory ISGs, did not show memory. Surprisingly, mechanistic analysis showed that IFN memory was not due to enhanced IFN signaling or retention of transcription factors on the ISGs. We demonstrated that this memory was attributed to accelerated recruitment of RNA polymerase II and transcription/chromatin factors, which coincided with acquisition of the histone H3.3 and H3K36me3 chromatin marks on memory ISGs. Similar memory was observed in bone marrow macrophages after IFNγ stimulation, suggesting that IFN stimulation modifies the shape of the innate immune response. Together, external signals can establish epigenetic memory in mammalian cells that imparts lasting adaptive performance upon various somatic cells.
  • Ryota Ouda, Naoyuki Sarai, Vishal Nehru, Mira C. Patel, Maxime Debrosse, Mahesh Bachu, Răzvan V. Chereji, Peter R. Eriksson, David J. Clark, Keiko Ozato
    FEBS Letters 592 10 1681 - 1692 2018年05月01日 [査読有り][通常論文]
     
    The role of the histone chaperone SPT6 in mammalian cells is not fully understood. Here, we investigated the involvement of SPT6 in type I interferon (IFN)-induced transcription in murine fibroblasts. In RNA-seq analysis, Spt6 siRNA attenuates about half of ~ 200 IFN-stimulated genes (ISGs), while not affecting housekeeping genes. ISGs with high mRNA induction are more susceptible to Spt6 siRNA than those with lower levels of induction. ChIP analysis shows that SPT6 is recruited to highly inducible, Spt6 siRNA-sensitive ISGs, but not to other siRNA-insensitive ISGs. Furthermore, SPT6 recruitment is abrogated in cells lacking the histone methyltransferase NSD2. In co-IP experiments, SPT6 interacts with NSD2. In summary, SPT6 facilitates IFN-induced transcription, highlighting its critical role in gene activation.
  • Nazmul Haque, Ryota Ouda, Keiko Ozato, J.Robert Hogg
    Nature Communication 9 1145 1145  2018年03月 [査読有り][通常論文]
  • Ruibo Li, Ryo Narita, Hiroshi Nishimura, Shinsuke Marumoto, Seiji P. Yamamoto, Ryota Ouda, Mitsuyoshi Yatagai, Takashi Fujita, Takashi Watanabe
    ACS Sustainable Chemistry and Engineering 6 1 119 - 126 2018年01月02日 [査読有り][通常論文]
     
    Pyroligneous acids (PA) from hardwood, softwood, and bamboo significantly disinfected encephalomyocarditis virus (EMCV). Twenty-five kinds of phenolic derivatives in the PAs were identified and quantified. The total amounts of phenolic compounds in bamboo PA is higher than those in the PAs from softwood and hardwood. Phenol, 2-methoxyphenol, 2-methoxy-4-methylphenol, and 2-methoxy-4-ethylphenol are the most abundant compounds in the PAs examined. The activities of all the phenolic compounds against the encephalomyocarditis virus were assessed. The number of phenolic hydroxyl groups significantly affects the antiviral activity, and catechol and its derivatives exhibit higher viral inhibition effects than other phenolic derivatives. In addition, substituents affect the antiviral activity of the compounds. Phenolic compounds with a methyl group show higher activities than with a methoxyl group (e.g., 2-methylphenol > 2-methoxyphenol). Moreover, the relative position of functional groups also plays a key role in the viral inhibition activity (e.g., 2,6-dimethoxyphenol > 3,4-dimethoxyphenol). Thus, PAs contain phenol derivatives with considerable structural diversity and viral inhibition activities, providing a new strategy for virus-inactivation treatment through the optimization of PA-derived phenol structures.
  • Li Ruibo, Narita Ryo, Ouda Ryota, Kimura Chihiro, Nishimura Hiroshi, Yatagai Mitsuyoshi, Fujita Takashi, Watanabe Takashi
    RSC ADVANCES 8 63 35888 - 35896 2018年 [査読有り][通常論文]
  • Ji-Seung Yoo, Kiyohiro Takahasi, Chen Seng Ng, Ryota Ouda, Koji Onomoto, Mitsutoshi Yoneyama, Janice Ching Lai, Simon Lattmann, Yoshikuni Nagamine, Tadashi Matsui, Kuniyoshi Iwabuchi, Hiroki Kato, Takashi Fujita
    PLOS PATHOGENS 10 3 e1004012  2014年03月 [査読有り][通常論文]
     
    RIG-I is a DExD/H-box RNA helicase and functions as a critical cytoplasmic sensor for RNA viruses to initiate antiviral interferon (IFN) responses. Here we demonstrate that another DExD/H-box RNA helicase DHX36 is a key molecule for RIG-I signaling by regulating double-stranded RNA (dsRNA)-dependent protein kinase (PKR) activation, which has been shown to be essential for the formation of antiviral stress granule (avSG). We found that DHX36 and PKR form a complex in a dsRNA-dependent manner. By forming this complex, DHX36 facilitates dsRNA binding and phosphorylation of PKR through its ATPase/helicase activity. Using DHX36 KO-inducible MEF cells, we demonstrated that DHX36 deficient cells showed defect in IFN production and higher susceptibility in RNA virus infection, indicating the physiological importance of this complex in host defense. In summary, we identify a novel function of DHX36 as a critical regulator of PKR-dependent avSG to facilitate viral RNA recognition by RIG-I-like receptor (RLR).
  • Ryota Ouda, Koji Onomoto, Kiyohiro Takahasi, Michael R. Edwards, Hiroki Kato, Mitsutoshi Yoneyama, Takashi Fujita
    JOURNAL OF BIOLOGICAL CHEMISTRY 286 29 26210 - U901 2011年07月 [査読有り][通常論文]
     
    In mammals, viral infections are detected by innate immune receptors, including Toll-like receptor and retinoic acid inducible gene I (RIG-I)-like receptor (RLR), which activate the type I interferon (IFN) system. IFN essentially activates genes encoding antiviral proteins that inhibit various steps of viral replication as well as facilitate the subsequent activation of acquired immune responses. In this study, we investigated the expression of non-coding RNA upon viral infection or RLR activation. Using a microarray, we identified several microRNAs (miRNA) specifically induced to express by RLR signaling. As suggested by Bioinformatics (miRBase Target Data base), one of the RLR-inducible miRNAs, miR-23b, actually knocked down the expression of very low density lipoprotein receptor (VLDLR) and LDLR-related protein 5 (LRP5). Transfection of miR-23b specifically inhibited infection of rhinovirus 1B (RV1B), which utilizes the low density lipoprotein receptor (LDLR) family for viral entry. Conversely, introduction of anti-miRNA-23b enhanced the viral yield. Knockdown experiments using small interfering RNA (siRNA) revealed that VLDLR, but not LRP5, is critical for an efficient infection by RV1B. Furthermore, experiments with the transfection of infectious viral RNA revealed that miR-23b did not affect post-entry viral replication. Our results strongly suggest that RIG-I signaling results in the inhibitions of infections of RV1B through the miR-23b-mediated down-regulation of its receptor VLDLR.

その他活動・業績

  • Microwave-assisted degradation of woody biomass for application as antiviral agent against encephalomycarditis virus
    Ruibo Li, Ryota Ouda, Chihiro Kimura, Hiroshi Nishimura, Takashi Fujita, Takashi Watanabe 1st International Lignin Symposium (ILS), 20190914, Hokkaido Univ. 2019年09月 [査読無し][通常論文]
  • Antiviral activity of phenolic compounds in pyroligenous acid, and structure-activity relationship
    Ruibo Li, Ryo Narita, Ryota Ouda, Chihiro Kimura, Hiroshi Nishimura, Takashi Fujita, Takashi Watanabe The 20th ISWFPC (poster) 2019年09月 [査読無し][通常論文]
  • Production of antiviral compounds from sugarcane bagasse by microwave solvolysis
    Chihiro Kimura, Ruibo Li, Ryota Ouda, Hiroshi Nishimura, Takashi Fujita, Takashi Watanabe The 20th ISWFPC (poster) 2019年09月 [査読無し][通常論文]
  • Conversion of woody biomass into antiviral compounds by microwave degradation
    Ruibo Li, Ryota Ouda, Chihiro Kimura, Ryo Narita, Hiroshi Nishimura, Takashi Fujita, Takashi Watanabe 第69回木材学会大会要旨集(口頭、函館、3.14.) 2019年03月 [査読無し][通常論文]
  • サトウキビバガスのマイクロ波ソルボリシスによる新規抗ウイルス活性物質の創出
    木村智洋, 李瑞波, 應田涼太, 西村裕志, 藤田尚志, 渡辺隆司 第69回木材学会大会要旨集(口頭、函館、3.14.) 2019年03月 [査読無し][通常論文]
  • Production of Antiviral Compounds from Sugarcane Bagasse by Microwave Reactions
    Chihiro Kimura, Ryota Ouda, Ruibo Li, Hiroshi Nishimura, Takashi Fujita, Takashi Watanabe The 3rd Asia Research Node Symposium on Humanosphere Science, NCHU, Taiwan, 20180926: P16 2018年09月 [査読無し][通常論文]
  • マイクロ波反応を用いたサトウキビバガス からの抗ウイルス活性物質の生産
    木村智洋, 李瑞波, 応田涼太, 西村裕志, 藤田尚志, 渡辺隆司 第27回日本エネルギー学会大会(poster P-3-5) 2018年08月 [査読無し][通常論文]
  • Characterization of antiviral compounds in wood and bamboo vinegars
    Ruibo Li, Ryo Narita, Hiroshi Nishimura, Shinsuke Marumoto, Seiji P. Yamamoto, Ryota Ouda, Mitsuyoshi Yatagai, Takashi Fujita, Takashi Watanabe International workshop of bamboo charcoal and vinegar 2017年12月 [査読無し][通常論文]
  • 應田涼太, LI Ruibo, 成田亮, 成田亮, 成田亮, 渡辺隆司 生存圏研究 (13) 34‐38 -47 2017年11月10日 [査読無し][通常論文]
     
    地球温暖化などによる環境変動や、グローバル化による人・動物・物の移動が増加したことから、近年ウイルスをはじめとした感染症のリスクが高まっている。本稿では、再生可能な持続資源として注目を集めている木質バイオマスの中で、木竹酢液の生理活性に着目した研究成果を紹介する。木竹酢液は、木竹炭を製造する際に副次的に得られ、セルロース、ヘミセルロースおよびリグニンの熱分解生成物などから構成される。木竹酢液は古くから消毒、殺菌などに使用されており、様々な生理活性を有するバイオマスであるが、ウイルスなどの病原体に対する活性についての検討は十分ではない。そこで、未利用バイオマスから薬効成分・生理活性物質を生産し、人の健康や安全な生活に貢献するという新しい研究領域を開拓することを目的として著者らが最近行っている、木酢液、竹酢液の抗ウイルス活性についての成果も併せて紹介する。とりわけ、2010年に宮崎県で発生した家畜伝染病、口蹄疫の原因ウイルスである口蹄疫ウイルスなどに対する消毒薬への応用を視野に入れ、木竹酢液に含まれる抗ウイルス活性物質の探索を行った結果について詳述する。これまでに、口蹄疫ウイルスと同じピコルナウイルス科に属する脳心筋炎ウイルスを用いて木竹酢液の抗ウイルス活性の検討を行い、木竹酢液は酸性条件下で強い抗ウイルス活性を示すことが明らかになっている。また、木竹酢液に含まれるphenolと酢酸が相乗的に抗ウイルス活性を示すことを示した。われわれの実験結果では、ヒノキ由来の木酢液原液が中性条件下においても抗ウイルス活性を示したことから、この画分に含まれる抗ウイルス活性物質の探索を行った。成分分画と抗ウイルス活性の検討により、精製したフラクションに抗ウイルス活性物質が含まれることを示した。本稿では、研究課題に関連する今後の展望についても簡単に言及する。
  • Ryota Ouda, Koji Onomoto, Kiyohiro Takahasi, Hiroki Kato, Mitstoshi Yoneyama, Takashi Fujita CYTOKINE 63 (3) 288 -288 2013年09月 [査読無し][通常論文]
  • Antiviral MicroRNA
    Ouda Ryota, Fujita Takashi Chembiomolecular Science 201 -205 2013年 [査読無し][通常論文]
  • 應田涼太, 藤田尚志 医学のあゆみ 243 (1) 12 -17 2012年10月06日 [査読無し][通常論文]
  • DHX36 regulates stress granule-mediated innate immunity during virus infection.
    Yoo J-S, Ouda R, Takahasi K, Kato H, Nagamine Y, Fujita T 10th NTU-KU Joint Symposium on Molecular and Cell Biology 1. 5-9 2012 Taipei, Taiwan 2012年 [査読有り][通常論文]
  • RIG-I-inducible miR-23b inhibits infections by minor group rhinoviruses through \ndown-regulation of the receptor VLDL.
    Ouda R, Onomoto K, Takahasi K, Edwards M.R, Kato H, Yoneyama M, Fujita T The 18th East Asia Joint Symposium on Biomedical Research Dec. 7-9, 2011 Shanghai, China 2011年 [査読有り][通常論文]
  • Functional analysis of RIG-I inducible microRNA.
    Ryota Ouda, Koji Onomoto, Mitsutoshi Yoneyama, Takashi Fujita 2009. 12.H 第32 回日本分子生物学会年会 横浜 2009年 [査読有り][通常論文]

受賞

  • 日本インターフェロン・サイトカイン学会 優秀ポスター賞
     
    受賞者: 應田 涼太

教育活動情報

主要な担当授業

  • 基本医学研究
    開講年度 : 2021年
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 炎症、自然免疫系、獲得免疫系、抗原提示機能、MHC、がん免疫、腸管免疫、炎症性疾患
  • 基本医学総論
    開講年度 : 2021年
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 免疫学、自然免疫、獲得免疫、炎症、感染免疫、がん免疫 Immunology, innate Immunity, adaptive immunity, inflammation, infection immunity, cancer immunology
  • 医学総論
    開講年度 : 2021年
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 免疫学、自然免疫、獲得免疫、炎症、感染免疫、がん免疫
  • 基盤医学研究
    開講年度 : 2021年
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 炎症、自然免疫系、獲得免疫系、抗原提示機能、MHC、がん免疫、腸管免疫、炎症性疾患
  • 微生物・免疫学実習
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 医学部
    キーワード : 細菌、ウイルス、無菌操作、グラム染色、抗酸菌染色、培養、細胞培養、定量、抗生物質、CPE、PCR、ELISA、IFA、蛍光抗体法、抗体、ブロッティング、炎症性サイトカイン、フローサイトメトリー、リンパ球、マクロファージ
  • 免疫学
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 医学部
    キーワード : 免疫学、自然免疫、獲得免疫、炎症、感染免疫、がん免疫


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