Updated on 2024/10/07

写真b

 
HANADA Yuki
 
*Items subject to periodic update by Rikkyo University (The rest are reprinted from information registered on researchmap.)
Affiliation*
College of Science Department of Life Science
Title*
Assistant Professor
Degree
Doctor of Medical Science ( 3 2021   Kyushu University )
Research Interests
  • Molecular cell biology at the surface of organelle membranes

  • Membrane protein

  • Mff

  • Energy sensing

  • Mitochondrial fission/fusion

  • Metabolism

  • Immune response

  • Mitochondria

  • Campus Career*
    • 4 2023 - Present 
      College of Science   Department of Life Science   Assistant Professor
     

    Research Areas

    • Life Science / Cell biology

    • Life Science / Metabolism and endocrinology

    Research History

    • 4 2023 - Present 
      Rikkyo University   Department of Life Science   Assistant professor

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      Notes:Laboratory of Molecular Cell Biology

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    • 4 2019 - 3 2023 
      Osaka University   Graduate School of Science Department of Biological Sciences   Researcher

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      Notes:Laboratory of Cellular Life Science

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    Education

    • 5 2018 - 3 2020 
      Osaka University   Graduate School of Science   Department of Biological Sciences

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    • 4 2015 - 3 2020 
      Kyushu University   Faculty of Medical Sciences

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    • 4 2009 - 3 2015 
      Kyushu University   School of Pharmaceutical Sciences

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    Awards

    • 9 2018  
      the 91st Annual Meeting of the Japanese Biochemical Society  Young Scientist Award 

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      Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

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    Papers

    • Alternative splicing of Mff regulates AMPK-mediated phosphorylation, mitochondrial fission and antiviral response Invited Peer-reviewed

      Yuki Hanada, Risa Maeda, Takaya Ishihara, Masaki Nakahashi, Yuichi Matsushima, Emi Ogasawara, Toshihiko Oka, Naotada Ishihara

      Pharmacological Research   107414 - 107414   9 2024

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      Authorship:Lead author   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

      DOI: 10.1016/j.phrs.2024.107414

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    • Non-alcoholic fatty liver disease in mice with hepatocyte-specific deletion of mitochondrial fission factor Peer-reviewed International journal

      Yukina Takeichi, Takashi Miyazawa, Shohei Sakamoto, Yuki Hanada, Lixiang Wang, Kazuhito Gotoh, Keiichiro Uchida, Shunsuke Katsuhara, Ryuichi Sakamoto, Takaya Ishihara, Keiji Masuda, Naotada Ishihara, Masatoshi Nomura, Yoshihiro Ogawa

      Diabetologia64 ( 9 ) 2092 - 2107   9 2021

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      Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

      Abstract

      Aims/hypothesis

      Mitochondria are highly dynamic organelles continuously undergoing fission and fusion, referred to as mitochondrial dynamics, to adapt to nutritional demands. Evidence suggests that impaired mitochondrial dynamics leads to metabolic abnormalities such as non-alcoholic steatohepatitis (NASH) phenotypes. However, how mitochondrial dynamics are involved in the development of NASH is poorly understood. This study aimed to elucidate the role of mitochondrial fission factor (MFF) in the development of NASH.

      Methods

      We created mice with hepatocyte-specific deletion of MFF (MffLiKO). MffLiKO mice fed normal chow diet (NCD) or high-fat diet (HFD) were evaluated for metabolic variables and their livers were examined by histological analysis. To elucidate the mechanism of development of NASH, we examined the expression of genes related to endoplasmic reticulum (ER) stress and lipid metabolism, and the secretion of triacylglycerol (TG) using the liver and primary hepatocytes isolated from MffLiKO and control mice.

      Results

      MffLiKO mice showed aberrant mitochondrial morphologies with no obvious NASH phenotypes during NCD, while they developed full-blown NASH phenotypes in response to HFD. Expression of genes related to ER stress was markedly upregulated in the liver from MffLiKO mice. In addition, expression of genes related to hepatic TG secretion was downregulated, with reduced hepatic TG secretion in MffLiKO mice in vivo and in primary cultures of MFF-deficient hepatocytes in vitro. Furthermore, thapsigargin-induced ER stress suppressed TG secretion in primary hepatocytes isolated from control mice.

      Conclusions/interpretation

      We demonstrated that ablation of MFF in liver provoked ER stress and reduced hepatic TG secretion in vivo and in vitro. Moreover, MffLiKO mice were more susceptible to HFD-induced NASH phenotype than control mice, partly because of ER stress-induced apoptosis of hepatocytes and suppression of TG secretion from hepatocytes. This study provides evidence for the role of mitochondrial fission in the development of NASH.

      Graphical abstract

      DOI: 10.1007/s00125-021-05488-2

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      Other Link: https://link.springer.com/article/10.1007/s00125-021-05488-2/fulltext.html

    • Dynamin-related protein 1 deficiency accelerates lipopolysaccharide-induced acute liver injury and inflammation in mice Peer-reviewed

      Lixiang Wang, Xin Li, Yuki Hanada, Nao Hasuzawa, Yoshinori Moriyama, Masatoshi Nomura, Ken Yamamoto

      Communications Biology4   894   21 7 2021

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      Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

      <title>Abstract</title>Mitochondrial fusion and fission, which are strongly related to normal mitochondrial function, are referred to as mitochondrial dynamics. Mitochondrial fusion defects in the liver cause a non-alcoholic steatohepatitis-like phenotype and liver cancer. However, whether mitochondrial fission defect directly impair liver function and stimulate liver disease progression, too, is unclear. Dynamin-related protein 1 (DRP1) is a key factor controlling mitochondrial fission. We hypothesized that DRP1 defects are a causal factor directly involved in liver disease development and stimulate liver disease progression. Drp1 defects directly promoted endoplasmic reticulum (ER) stress, hepatocyte death, and subsequently induced infiltration of inflammatory macrophages. Drp1 deletion increased the expression of numerous genes involved in the immune response and DNA damage in <italic>Drp1</italic>LiKO mouse primary hepatocytes. We administered lipopolysaccharide (LPS) to liver-specific <italic>Drp1</italic>-knockout (<italic>Drp1</italic>LiKO) mice and observed an increased inflammatory cytokine expression in the liver and serum caused by exaggerated ER stress and enhanced inflammasome activation. This study indicates that Drp1 defect-induced mitochondrial dynamics dysfunction directly regulates the fate and function of hepatocytes and enhances LPS-induced acute liver injury in vivo.

      DOI: 10.1038/s42003-021-02413-6

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      Other Link: http://www.nature.com/articles/s42003-021-02413-6

    • MAVS is energized by Mff which senses mitochondrial metabolism via AMPK for acute antiviral immunity Peer-reviewed International journal

      Yuki Hanada, Naotada Ishihara, Lixiang Wang, Hidenori Otera, Takaya Ishihara, Takumi Koshiba, Katsuyoshi Mihara, Yoshihiro Ogawa, Masatoshi Nomura

      Nature Communications11 ( 1 ) 5711 - 5711   11 11 2020

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

      Mitochondria are multifunctional organelles that produce energy and are critical for various signaling pathways. Mitochondrial antiviral signaling (MAVS) is a mitochondrial outer membrane protein essential for the anti-RNA viral immune response, which is regulated by mitochondrial dynamics and energetics; however, the molecular link between mitochondrial metabolism and immunity is unclear. Here we show in cultured mammalian cells that MAVS is activated by mitochondrial fission factor (Mff), which senses mitochondrial energy status. Mff mediates the formation of active MAVS clusters on mitochondria, independent of mitochondrial fission and dynamin-related protein 1. Under mitochondrial dysfunction, Mff is phosphorylated by the cellular energy sensor AMP-activated protein kinase (AMPK), leading to the disorganization of MAVS clusters and repression of the acute antiviral response. Mff also contributes to immune tolerance during chronic infection by disrupting the mitochondrial MAVS clusters. Taken together, Mff has a critical function in MAVS-mediated innate immunity, by sensing mitochondrial energy metabolism via AMPK signaling.

      DOI: 10.1038/s41467-020-19287-7

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    • Nivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanoma Peer-reviewed

      Seiichi Yano, Kenji Ashida, Hiromi Nagata, Kenji Ohe, Naoko Wada, Yukina Takeichi, Yuki Hanada, Yuta Ibayashi, Lixiang Wang, Shohei Sakamoto, Ryuichi Sakamoto, Hiroshi Uchi, Motoaki Shiratsuchi, Masutaka Furue, Masatoshi Nomura, Yoshihiro Ogawa

      BMC Endocrine Disorders18 ( 36 )   8 6 2018

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      Publishing type:Research paper (scientific journal)  

      © 2018 The Author(s). Background: Nivolumab, an anti-programmed cell death-1 monoclonal antibody, has improved the survival of patients with malignant melanoma. Despite its efficacy, nivolumab inconsistently induces thyroid dysfunction as an immune-related adverse event (irAE). This study aimed to evaluate nivolumab-induced thyroid dysfunction to determine the risks and mechanisms of thyroid irAEs. Methods: After excluding 10 patients, data of 24 patients with malignant melanoma (aged 17-85years; 54% female) were retrospectively analyzed. Results: Thyroid irAEs were observed in seven patients (29%). Three patients had hypothyroidism after preceding transient thyrotoxicosis, and the other four patients had hypothyroidism without thyrotoxicosis. Levothyroxine-Na replacement was required in three patients. Antithyroid antibody (ATA) titer was elevated in one of four assessable patients. The average (±SD) time to onset of thyroid irAE was 33.6 (±21.9) weeks. The administration period of nivolumab was longer in patients with thyroid irAEs than in those without thyroid irAEs (P<0.01). There were no significant differences between patients with and without thyroid irAEs regarding age, sex, tumor stage, response to nivolumab therapy, baseline thyroid function, antithyroid peroxidase antibody (anti-TPO Ab) and antithyroglobulin antibody (anti-Tg Ab). Conclusions: Thyroid dysfunction was a common irAE of nivolumab in malignant melanoma. Neither anti-TPO Ab nor anti-Tg Ab was associated with the risk for nivolumab-induced thyroid dysfunction. A conventional ATA-independent mechanism might be involved in thyroid irAEs. Further studies are required to clarify the mechanism and identify the predictive factors of thyroid irAEs.

      DOI: 10.1186/s12902-018-0267-x

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    • Vancomycin induces reactive oxygen species-dependent apoptosis via mitochondrial cardiolipin peroxidation in renal tubular epithelial cells Peer-reviewed

      Yuya Sakamoto, Takahisa Yano, Yuki Hanada, Aki Takeshita, Fumika Inagaki, Satohiro Masuda, Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo

      European Journal of Pharmacology800   48 - 56   4 2017

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      Publishing type:Research paper (scientific journal)  

      © 2017 The Authors Vancomycin (VCM) is a first-line antibiotic for serious infections caused by methicillin-resistant Staphylococcus aureus. However, nephrotoxicity is one of the most complaint in VCM therapy. We previously reported that VCM induced apoptosis in a porcine proximal tubular epithelial cell line (LLC-PK1), in which mitochondrial complex I may generate superoxide, leading to cell death. In the present study, VCM caused production of mitochondrial reactive oxygen species and peroxidation of the mitochondrial phospholipid cardiolipin that was reversed by administration of the mitochondrial uncoupler carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP). FCCP also significantly suppressed VCM-induced depolarization of the mitochondrial membrane and apoptosis. Moreover, the lipophilic antioxidant vitamin E and a mitochondria-targeted antioxidant, mitoTEMPO, also significantly suppressed VCM-induced depolarization of mitochondrial membrane and apoptosis, whereas vitamin C, n-acetyl cysteine, or glutathione did not provide significant protection. These findings suggest that peroxidation of the mitochondrial membrane cardiolipin mediated the VCM-induced production of intracellular reactive oxygen species and initiation of apoptosis in LLC-PK1 cells. Furthermore, regulation of mitochondrial function using a mitochondria-targeted antioxidant, such as mitoTEMPO, may constitute a potential strategy for mitigation of VCM-induced proximal tubular epithelial cell injury.

      DOI: 10.1016/j.ejphar.2017.02.025

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    • Disruption of mitochondrial fission in the liver protects mice from diet-induced obesity and metabolic deterioration Peer-reviewed

      Lixiang Wang, Takaya Ishihara, Yuta Ibayashi, Keita Tatsushima, Daiki Setoyama, Yuki Hanada, Yukina Takeichi, Shohei Sakamoto, Sadaki Yokota, Katsuyoshi Mihara, Dongchon Kang, Naotada Ishihara, Ryoichi Takayanagi, Masatoshi Nomura

      Diabetologia58 ( 10 ) 2371 - 2380   24 10 2015

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      Publishing type:Research paper (scientific journal)  

      © 2015, Springer-Verlag Berlin Heidelberg. Aim/hypothesis: Mitochondria and the endoplasmic reticulum (ER) physically interact by close structural juxtaposition, via the mitochondria-associated ER membrane. Inter-organelle communication between the ER and mitochondria has been shown to regulate energy metabolism and to be central to the modulation of various key processes such as ER stress. We aimed to clarify the role of mitochondrial fission in this communication. Methods: We generated mice lacking the mitochondrial fission protein dynamin-related protein 1 (DRP1) in the liver (Drp1LiKO mice). Results: Drp1LiKO mice showed decreased fat mass and were protected from high-fat diet (HFD)-induced obesity. Analysis of liver gene expression profiles demonstrated marked elevation of ER stress markers. In addition, we observed increased expression of the fibroblast growth factor 21 (FGF21) gene through induction of activating transcription factor 4, master regulator of the integrated stress response. Conclusions/interpretation: Disruption of mitochondrial fission in the liver provoked ER stress, while inducing the expression of FGF21 to increase energy expenditure and protect against HFD-induced obesity.

      DOI: 10.1007/s00125-015-3704-7

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    Misc.

    • Molecular mechanism linking metabolism and innate immunity on mitochondria Peer-reviewed

      Yuki Hanada, Takaya Ishihara, Naotada Ishihara

      Journal of Japanese Biochemical Society94 ( 2 ) 230 - 235   25 4 2022

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      Authorship:Lead author   Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

      DOI: 10.14952/SEIKAGAKU.2022.940230

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    • Regulation of cellular functions by mitochondrial membrane dynamics

      Yuki Hanada, Takaya Ishihara, Naotada Ishihara

      Seitai no Kagaku69 ( 6 ) 581 - 585   12 2018

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      Authorship:Lead author   Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

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    Presentations

    • Mitochondrial outer membrane proteins regulated by energy metabolism for signaling at the mitochondrial surface Invited International conference

      Yuki Hanada

      Cold Spring Harbor Asia Conference, Mitochondria and Metabolism in Health and Disease  1 11 2023 

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      Event date: 30 10 2023 - 3 11 2023

      Language:English   Presentation type:Oral presentation (invited, special)  

      Venue:Suzhou  

      I was selected as a chairperson of the session in this conference.

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    • エネルギー代謝と免疫応答を繋ぐ ミトコンドリアの新機能

      花田有希

      立教大学 理学部 生命理学科 助教セミナー  13 10 2023 

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    • Splicing-dependent functional regulation of mitochondrial fission factor Mff

      30 6 2022 

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      Event date: 28 6 2022 - 30 6 2022

      Language:English   Presentation type:Poster presentation  

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    • Two-sided control of antiviral response by mitochondrial immunometabolic factor Invited

      Yuki Hanada, Masatoshi Nomura, Yoshihiro Ogawa, Naotada Ishihara

      The 44th Annual Meeting of the Molecular Biology Society of Japan  2 12 2021 

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      Event date: 1 12 2021 - 3 12 2021

      Language:English   Presentation type:Symposium, workshop panel (nominated)  

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    • Molecular property of mitochondrial fission factor Mff for mitochondrial antiviral signaling

      3 11 2021 

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      Event date: 3 11 2021 - 5 11 2021

      Language:Japanese   Presentation type:Poster presentation  

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    • Regulatory mechanism of mitochondrial immune response against RNA virus infection International conference

      Yuki Hanada, Risa Maeda, Yoshihiro Ogawa, Masatoshi Nomura, Naotada Ishihara

      25 12 2020 

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      Event date: 25 12 2020 - 26 12 2020

      Language:English   Presentation type:Oral presentation (general)  

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    • Regulatory function of mitochondrial fission factor Mff in mitochondrial antiviral response

      26 6 2019 

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      Event date: 25 6 2019 - 26 6 2019

      Language:Japanese   Presentation type:Oral presentation (general)  

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    • ミトコンドリアを介した抗ウイルス応答におけるミトコンドリア分裂因子Mffの新たな調節機能

      花田 有希

      ミトコンドリアサイエンスワークショップ2019  14 5 2019 

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      Event date: 14 5 2019 - 15 5 2019

      Language:Japanese   Presentation type:Oral presentation (general)  

      Venue:亀岡, 京都  

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    • A novel regulatory function of mitochondrial fission factor Mff in mitochondrial antiviral activity

      Yuki Hanada, Takaya Ishihara, Masatoshi Nomura, Yoshihiro Ogawa, Naotada Ishihara

      26 9 2018 

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      Event date: 24 9 2018 - 26 9 2018

      Language:Japanese   Presentation type:Oral presentation (general)  

      Young Scientist Award

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    • Involvement of mitochondrial fission factor (Mff) in MAVS dissociation from mitochondria for a time-dependent induction of antiviral responses International conference

      Yuki Hanada, Lixiang Wang, Hidenori Otera, Takumi Koshiba, Syohei Sakamoto, Kenji Ashida, Naotada Ishihara, Katsuyoshi Mihara, Yoshihiro Ogawa, Masatoshi Nomura

      20 4 2018 

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      Event date: 20 4 2018 - 22 4 2018

      Language:English   Presentation type:Poster presentation  

      Venue:Kyoto  

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    Teaching Experience

    • 2023 - Present 
      Experiments in Biology for Chemistry Students ( Rikkyo University )

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    • 2023 - Present 
      Laboratory Experiments in Life Science 2B ( Rikkyo University )

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    • 2023 - Present 
      Seminar in Life Science 2 ( Rikkyo University )

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    • 2023 - Present 
      Basic Experiments in Life Science ( Rikkyo University )

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    • 2023 - Present 
      Research Experiments ( Rikkyo University )

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    Professional Memberships

    • 2024 - Present 
      The Japanese Society of Mitochondrial Research and Medicine (J-mit)

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    • 2023 - Present 
      The Molecular Biology Society of Japan

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    • 2019 - Present 
      Japan Society for Cell Biology

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    • 2017 - Present 
      The Japanese Biochemical Society

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    • 2015 - Present 
      The Japan Endocrine Society

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    • 2014 - Present 
      The Pharmaceutical Society of Japan

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    Research Projects

    • Regulatory mechanism of mitochondrial function on mitochondrial outer membrane, the interface with the host

      the Japan Society for the Promotion of Science (JSPS)  Grants-in-Aid for Scientific Research (KAKENHI) 

      Yuki Hanada

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      2023 - 2024

      Grant number:23K19355

      Authorship:Principal investigator 

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    • Mitochondria-mediated metabolism-immune linkage for protection against viral infection

      Robert T. Huang Entrepreneurship Center of Kyushu University (QREC)  Academic Challenge 2017 grants-in-aid for scientific research 

      Yuki Hanada

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      5 2017 - 3 2018

      Authorship:Principal investigator 

      Grant amount:\497000

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    Academic Activities

    • Journal of Biochemistry reviewer

      Peer review

      2023

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    Media Coverage

    • Mitochondria regulate strength of immune response Newspaper, magazine

      The Mainichi Newspapers  3 12 2020

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    • Mitochondrial protein modulates defense against viral infection Newspaper, magazine

      The Nikkan Kogyo Newspapers  12 11 2020

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    Other

    • Session 7 Chair in Cold Spring Harbor Asia Conference 2023

      11 2023
      -
      11 2023

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    • JSPS PD Research Fellowship (refusal to accept fellowship)

      9 2022
      -
      9 2022

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