Updated on 2024/03/09

写真a

 
Sasaki Fumiyuki
 
Affiliation
Faculty of Medicine, Department of Microbiology and Immunology, Assistant Professor
Title
Assistant Professor
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Degree

  • Doctor of Philosophy in Medicine ( 2013.3   Kyushu University )

  • Master's degree in Medical Science ( 2009.3   Kyushu University )

Research Interests

  • Gタンパク質共役型受容体(GPCR)

  • 生理活性脂質

  • メカノバイオロジー

  • インフラマソーム

  • 脂質代謝

  • 免疫応答

  • 炎症

Research Areas

  • Life Science / Sports sciences

  • Life Science / Pathological biochemistry

  • Life Science / Immunology

  • Life Science / Biomedical engineering

  • Life Science / Nutrition science and health science

Education

  • 九州大学大学院   医学系学府 医学専攻   博士(医学) 学位取得

    2013.3

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    Country: Japan

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  • Kyushu University

    2009.4 - 2013.3

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    Country: Japan

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  • Kyushu University

    2007.4 - 2009.3

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    Country: Japan

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  • Hirosaki University   Faculty of Agriculture and Life Science

    2005.4 - 2007.3

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    Country: Japan

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  • Tomakomai National College of Technology

    2000.4 - 2005.3

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    Country: Japan

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Research History

  • Nippon Medical School   Graduate School   Assistant Professor

    2022.9

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    Country:Japan

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  • Juntendo University School of Medicine   Department of Biochemistry

    2021.11

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    Country:Japan

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  • Nippon Medical School   Department of Microbiology and Immunology   Assistant Professor

    2021.4

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    Country:Japan

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  • Tokyo Medical and Dental University   Department of Cell Signaling, Graduate School of Medical and Dental Sciences   Project Researcher

    2017.8 - 2021.3

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    Country:Japan

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  • AMED-CREST   「骨恒常性を司る骨細胞のメカノ・カスケードの解明」   プロジェクト研究員

    2017.8 - 2021.3

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    Country:Japan

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  • Juntendo University School of Medicine   Faculty of Medicine

    2017.6 - 2017.7

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  • Institute of Molecular Biotechnology, Austria (IMBA)   Postdoctoral Fellow

    2015.4 - 2016.9

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    Country:Austria

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  • Juntendo University   Institute for Diseases of Old Age   Postdoctoral Researcher

    2013.4 - 2015.3

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    Country:Japan

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  • Juntendo University

    2013.4 - 2015.3

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    Country:Japan

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Professional Memberships

  • The Japanese Society of Inflammation and Regeneration

    2019.3

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  • The Japanese Conference on the Biochemistry of Lipids

    2009

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  • Japanease Society for Immunology

    2008.6

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  • The Japanese Biochemical Society

    2008

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Committee Memberships

  • Frontiers In Immunology   Review Editor  

    2023.9   

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    Committee type:Other

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Papers

  • Expression of leukotriene B4 receptor 1 defines functionally distinct DCs that control allergic skin inflammation Reviewed International journal

    Tomoaki Koga, Fumiyuki Sasaki, Kazuko Saeki, Soken Tsuchiya, Toshiaki Okuno, Mai Ohba, Takako Ichiki, Satoshi Iwamoto, Hirotsugu Uzawa, Keiko Kitajima, Chikara Meno, Eri Nakamura, Norihiro Tada, Yoshinori Fukui, Junichi Kikuta, Masaru Ishii, Yukihiko Sugimoto, Mitsuyoshi Nakao, Takehiko Yokomizo

    Cellular & Molecular Immunology   18 ( 6 )   1437 - 1449   2021.6

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

    <title>Abstract</title>Leukotriene B4 (LTB4) receptor 1 (BLT1) is a chemotactic G protein-coupled receptor expressed by leukocytes, such as granulocytes, macrophages, and activated T cells. Although there is growing evidence that BLT1 plays crucial roles in immune responses, its role in dendritic cells remains largely unknown. Here, we identified novel DC subsets defined by the expression of BLT1, namely, BLT1hi and BLT1lo DCs. We also found that BLT1hi and BLT1lo DCs differentially migrated toward LTB4 and CCL21, a lymph node-homing chemoattractant, respectively. By generating LTB4-producing enzyme LTA4H knockout mice and CD11c promoter-driven Cre recombinase-expressing BLT1 conditional knockout (BLT1 cKO) mice, we showed that the migration of BLT1hi DCs exacerbated allergic contact dermatitis. Comprehensive transcriptome analysis revealed that BLT1hi DCs preferentially induced Th1 differentiation by upregulating IL-12p35 expression, whereas BLT1lo DCs accelerated T cell proliferation by producing IL-2. Collectively, the data reveal an unexpected role for BLT1 as a novel DC subset marker and provide novel insights into the role of the LTB4-BLT1 axis in the spatiotemporal regulation of distinct DC subsets.

    DOI: 10.1038/s41423-020-00559-7

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    Other Link: https://www.nature.com/articles/s41423-020-00559-7

  • Mechanotransduction via the Piezo1-Akt pathway underlies Sost suppression in osteocytes Reviewed

    Fumiyuki Sasaki, Mikihito Hayashi, Yuki Mouri, Satoshi Nakamura, Taiji Adachi, Tomoki Nakashima

    Biochemical and Biophysical Research Communications   521 ( 3 )   806 - 813   2020.1

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    DOI: 10.1016/j.bbrc.2019.10.174

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  • Leukotriene B4 promotes neovascularization and macrophage recruitment in murine wet-type AMD models Reviewed International journal

    Fumiyuki Sasaki, Tomoaki Koga, Mai Ohba, Kazuko Saeki, Toshiaki Okuno, Keijiro Ishikawa, Takahito Nakama, Shintaro Nakao, Shigeo Yoshida, Tatsuro Ishibashi, Hamid Ahmadieh, Mozhgan Rezaei Kanavi, Ali Hafezi-Moghadam, Josef M. Penninger, Koh-Hei Sonoda, Takehiko Yokomizo

    JCI Insight   3 ( 18 )   2018.9

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:American Society for Clinical Investigation  

    Age-related macular degeneration (AMD), a progressive chronic disease of the central retina, is associated with aging and is a leading cause of blindness worldwide. Here, we demonstrate that leukotriene B4 (LTB4) receptor 1 (BLT1) promotes laser-induced choroidal neovascularization (CNV) in a mouse model for wet-type AMD. CNV was significantly less in BLT1-deficient (BLT1-KO) mice compared with BLT1-WT controls. Expression of several proangiogenic and profibrotic factors was lower in BLT1-KO eyes than in BLT1-WT eyes. LTB4 production in the eyes was substantially increased in the early phase after laser injury. BLT1 was highly expressed in M2 macrophages in vitro and in vivo, and ocular BLT1+ M2 macrophages were increased in the aged eyes after laser injury. Furthermore, M2 macrophages were rapidly attracted by LTB4 and subsequently produced VEGF-A- through BLT1-mediated signaling. Consequently, intravitreal injection of M2 macrophages augmented CNV formation, which was attenuated by BLT1 deficiency. Thus, laser-induced injury to the retina triggered LTB4 production and attracted M2 macrophages via BLT1, leading to development of CNV. A selective BLT1 antagonist (CP105696) and 3 LTB4 inhibitors (zileuton, MK-886, and bestatin) reduced CNV in a dose-dependent manner. CP105696 also inhibited the accumulation of BLT1+ M2 macrophages in the laser-injured eyes of aged mice. Together, these results indicate that the LTB4-BLT1 axis is a potentially novel therapeutic target for CNV of wet-type AMD.

    DOI: 10.1172/jci.insight.96902

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  • Forceful mastication activates osteocytes and builds a stout jawbone Reviewed International journal

    Masamu Inoue, Takehito Ono, Yoshitaka Kameo, Fumiyuki Sasaki, Takashi Ono, Taiji Adachi, Tomoki Nakashima

    Scientific Reports   9 ( 1 )   4404 - 4404   2019.12

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    Bone undergoes a constant reconstruction process of resorption and formation called bone remodeling, so that it can endure mechanical loading. During food ingestion, masticatory muscles generate the required masticatory force. The magnitude of applied masticatory force has long been believed to be closely correlated with the shape of the jawbone. However, both the mechanism underlying this correlation and evidence of causation remain largely to be determined. Here, we established a novel mouse model of increased mastication in which mice were fed with a hard diet (HD) to elicit greater masticatory force. A novel in silico computer simulation indicated that the masticatory load onto the jawbone leads to the typical bone profile seen in the individuals with strong masticatory force, which was confirmed by in vivo micro-computed tomography (micro-CT) analyses. Mechanistically, increased mastication induced Insulin-like growth factor (IGF)-1 and suppressed sclerostin in osteocytes. IGF-1 enhanced osteoblastogenesis of the cells derived from tendon. Together, these findings indicate that the osteocytes balance the cytokine expression upon the mechanical loading of increased mastication, in order to enhance bone formation. This bone formation leads to morphological change in the jawbone, so that the bone adapts to the mechanical environment to which it is exposed.

    DOI: 10.1038/s41598-019-40463-3

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    Other Link: http://www.nature.com/articles/s41598-019-40463-3

  • BLT1 mediates commensal bacteria-dependent innate immune signals to enhance antigen-specific intestinal IgA responses Reviewed International journal

    Takahiro Nagatake, So-ichiro Hirata, Tomoaki Koga, Etsushi Kuroda, Shingo Kobari, Hidehiko Suzuki, Koji Hosomi, Naomi Matsumoto, Yaulia Yanrismet, Michiko Shimojou, Sakiko Morimoto, Fumiyuki Sasaki, Ken J. Ishii, Takehiko Yokomizo, Jun Kunisawa

    Mucosal Immunology   12 ( 5 )   1082 - 1091   2019.9

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    Leukotriene B4 receptor 1 (BLT1) triggers the migration of granulocytes and activated T cells; however, its role in B-cell function remains unclear. Here we report that BLT1 is required to induce the production of antigen-specific IgA against oral vaccine through mediating innate immune signals from commensal bacteria. B cells acquire BLT1 expression during their differentiation to IgA+ B cells and plasma cells in Peyer's patches and the small intestinal lamina propria, respectively. BLT1 KO mice exhibited impaired production of antigen-specific fecal IgA to oral vaccine despite normal IgG responses to systemically immunized antigen. Expression of MyD88 was decreased in BLT1 KO gut B cells and consequently led to diminished proliferation of commensal bacteria-dependent plasma cells. These results indicate that BLT1 enhances the proliferation of commensal bacteria-dependent IgA+ plasma cells through the induction of MyD88 and thereby plays a key role in the production of antigen-specific intestinal IgA.

    DOI: 10.1038/s41385-019-0175-z

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    Other Link: http://www.nature.com/articles/s41385-019-0175-z

  • Biochemical and immunological characterization of a novel monoclonal antibody against mouse leukotriene B4 receptor 1

    Fumiyuki Sasaki, Tomoaki Koga, Kazuko Saeki, Toshiaki Okuno, Saiko Kazuno, Tsutomu Fujimura, Yasuyuki Ohkawa, Takehiko Yokomizo

    PLOS ONE   12 ( 9 )   e0185133 - e0185133   2017.9

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Public Library of Science (PLoS)  

    Leukotriene B-4 (LTB4) receptor 1 (BLT1) is a G protein-coupled receptor expressed in various leukocyte subsets; however, the precise expression of mouse BLT1 (mBLT1) has not been reported because a mBLT1 monoclonal antibody (mAb) has not been available. In this study, we present the successful establishment of a hybridoma cell line (clone 7A8) that produces a high-affinity mAb for mBLT1 by direct immunization of BLT1-deficient mice with mBLT1-overexpressing cells. The specificity of clone 7A8 was confirmed using mBLT1-overexpressing cells and mouse peripheral blood leukocytes that endogenously express BLT1. Clone 7A8 did not cross-react with human BLT1 or other G protein-coupled receptors, including human chemokine (C-X-C motif) receptor 4. The 7A8 mAb binds to the second extracellular loop of mBLT1 and did not affect LTB4 binding or intracellular calcium mobilization by LTB4. The 7A8 mAb positively stained Gr-1-positive granulocytes, CD11b-positive granulocytes/monocytes, F4/80-positive monocytes, CCR2-high and CCR2-low monocyte subsets in the peripheral blood and a CD4-positive T cell subset, Th1 cells differentiated in vitro from naive CD4-positive T cells. This mAb was able to detect Gr-1-positive granulocytes and monocytes in the spleens of naive mice by immunohistochemistry. Finally, intraperitoneal administration of 7A8 mAb depleted granulocytes and monocytes in the peripheral blood. We have therefore succeeded in generating a high-affinity anti-mBLT1 mAb that is useful for analyzing mBLT1 expression in vitro and in vivo.

    DOI: 10.1371/journal.pone.0185133

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  • Generation and characterization of a human-mouse chimeric high-affinity antibody that detects the DYKDDDDK FLAG peptide Reviewed

    Koki Ikeda, Tomoaki Koga, Fumiyuki Sasaki, Ayumi Ueno, Kazuko Saeki, Toshiaki Okuno, Takehiko Yokomizo

    Biochemical and Biophysical Research Communications   486 ( 4 )   1077 - 1082   2017.5

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    DOI: 10.1016/j.bbrc.2017.03.165

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  • Leukotriene B4 receptor type 2 (BLT2) enhances skin barrier function by regulating tight junction proteins Reviewed International journal

    Yumiko Ishii, Kazuko Saeki, Min Liu, Fumiyuki Sasaki, Tomoaki Koga, Keiko Kitajima, Chikara Meno, Toshiaki Okuno, Takehiko Yokomizo

    The FASEB Journal   30 ( 2 )   933 - 947   2016.2

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    GPCRs are involved in numerous physiologic functions and are important drug targets. Although the epithelial barrier is important for protection from invading pathogens, the correlation between GPCRs and epithelial barrier function remains unknown. Leukotriene B4 (LTB4) receptor type 2 (BLT2), mainly expressed in epithelial cells, is a GPCR for 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) and LTB4. In our study, BLT2 localized at the lateral membrane in BLT2-overexpressing Madin-Darby canine kidney (MDCK) II cells and in the small intestine of BLT2-transgenic mice. BLT2-deficient mice exhibited higher transepidermal water loss and were more sensitive to epicutaneous sensitization. MDCK-BLT2 cells recovered transepithelial electrical resistance (TER) after a calcium switch faster than did MDCK-Mock cells, and 12-HHT stimulation accelerated TER recovery only in MDCK-BLT2 cells. Quantitative PCR and immunoblot analyses revealed that the 12-HHT/BLT2 axis up-regulated claudin-4 (CLDN4) expression in MDCK-BLT2 cells and human primary keratinocytes, and CLDN4 knockdown abolished 12-HHT-dependent TER recovery. Acceleration of TER recovery and induction of CLDN4 expression by 12-HHT stimulation were abolished by inhibition of Gαi protein or p38 MAPK. These results show that 12-HHT/BLT2 enhances epithelial barrier function by increasing CLDN4 expression via the Gαi protein-p38 MAPK pathway.

    DOI: 10.1096/fj.15-279653

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    Other Link: https://onlinelibrary.wiley.com/doi/full-xml/10.1096/fj.15-279653

  • ROCK-Isoform-Specific Polarization of Macrophages Associated with Age-Related Macular Degeneration Reviewed International journal

    Souska Zandi, Shintaro Nakao, Kwang-Hoon Chun, Paolo Fiorina, Dawei Sun, Ryoichi Arita, Ming Zhao, Enoch Kim, Olivier Schueller, Stewart Campbell, Mahdi Taher, Mark Ivan Melhorn, Alexander Schering, Francesca Gatti, Sara Tezza, Fang Xie, Andrea Vergani, Shigeo Yoshida, Keijiro Ishikawa, Muneo Yamaguchi, Fumiyuki Sasaki, Ruth Schmidt-Ullrich, Yasuaki Hata, Hiroshi Enaida, Mitsuko Yuzawa, Takehiko Yokomizo, Young-Bum Kim, Paul Sweetnam, Tatsuro Ishibashi, Ali Hafezi-Moghadam

    Cell Reports   10 ( 7 )   1173 - 1186   2015.2

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    Age is a major risk factor in age-related macular degeneration (AMD), but the underlying cause is unknown. We find increased Rho-associated kinase (ROCK) signaling and M2 characteristics in eyes of aged mice, revealing immune changes in aging. ROCK isoforms determine macrophage polarization into M1 and M2 subtypes. M2-like macrophages accumulated in AMD, but not in normal eyes, suggesting that these macrophages may be linked to macular degeneration. M2 macrophages injected into the mouse eye exacerbated choroidal neovascular lesions, while M1 macrophages ameliorated them, supporting a causal role for macrophage subtypes in AMD. Selective ROCK2 inhibition with a small molecule decreased M2-like macrophages and choroidal neovascularization. ROCK2 inhibition upregulated M1 markers without affecting macrophage recruitment, underlining the plasticity of these macrophages. These results reveal age-induced innate immune imbalance as underlying AMD pathogenesis. Targeting macrophage plasticity opens up new possibilities for more effective AMD treatment.

    DOI: 10.1016/j.celrep.2015.01.050

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  • Leukotriene B4 receptor BLT2 negatively regulates allergic airway eosinophilia Reviewed

    Yuko Matsunaga, Satoru Fukuyama, Toshiaki Okuno, Fumiyuki Sasaki, Takehiko Matsunobu, Yukari Asai, Koichiro Matsumoto, Kazuko Saeki, Masahiro Oike, Yukari Sadamura, Kentaro Machida, Yoichi Nakanishi, Masato Kubo, Takehiko Yokomizo, Hiromasa Inoue

    The FASEB Journal   27 ( 8 )   3306 - 3314   2013.8

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    Leukotriene B4 (LTB4) has been implicated in the pathogenesis of allergic diseases. BLT2, a low-affinity LTB4 receptor, is activated by LTB4 and 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT). Although the high-affinity LTB4 receptor BLT1 has been shown to exert proinflammatory roles, the role of BLT2 in allergic inflammation has not been clarified. To study the function of BLT2 in development of asthma, we used mice model of ovalbumin (OVA)-induced allergic airway disease. The 12-HHT levels were elevated in bronchoalveolar lavage (BAL) fluids of OVA-sensitized/challenged wild-type mice. BLT2-deficient mice exhibited enhanced eosinophilia in BAL fluids after OVA exposure. Interleukin (IL)-13 levels in BAL fluids and IL-13-producing CD 4+ T cells in the lungs were elevated in BLT2-deficient mice compared to wild-type mice, whereas the levels of IL-4, IL-5, and interferon (IFN) in BAL fluids and serum OVA-specific IgE were comparable. Transfection of BLT2-specific small interfering RNA enhanced IL-13 production in CD4+ T cells in vitro. Expression of BLT2 mRNA in CD4+ T cells was significantly reduced in patients with asthma compared to healthy control subjects. These findings indicate that BLT2 has a protective role in allergic airway inflammation and that diminished BLT2 expression in CD4+ T cells may contribute to the pathophysiology of asthma. © FASEB.

    DOI: 10.1096/fj.12-217000

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    Other Link: https://onlinelibrary.wiley.com/doi/full-xml/10.1096/fj.12-217000

  • Absence of LTB4/BLT1 axis facilitates generation of mouse GM-CSF–induced long-lasting antitumor immunologic memory by enhancing innate and adaptive immune systems International journal

    Yosuke Yokota, Hiroyuki Inoue, Yumiko Matsumura, Haruka Nabeta, Megumi Narusawa, Ayumi Watanabe, Chika Sakamoto, Yasuki Hijikata, Mutsunori Iga-Murahashi, Koichi Takayama, Fumiyuki Sasaki, Yoichi Nakanishi, Takehiko Yokomizo, Kenzaburo Tani

    Blood   120 ( 17 )   3444 - 3454   2012.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:American Society of Hematology  

    <title>Abstract</title>
    BLT1 is a high-affinity receptor for leukotriene B4 (LTB4) that is a potent lipid chemoattractant for myeloid leukocytes. The role of LTB4/BLT1 axis in tumor immunology, including cytokine-based tumor vaccine, however, remains unknown. We here demonstrated that BLT1-deficient mice rejected subcutaneous tumor challenge of GM-CSF gene-transduced WEHI3B (WGM) leukemia cells (KO/WGM) and elicited robust antitumor responses against second tumor challenge with WEHI3B cells. During GM-CSF–induced tumor regression, the defective LTB4/BLT1 signaling significantly reduced tumor-infiltrating myeloid-derived suppressor cells, increased the maturation status of dendritic cells in tumor tissues, enhanced their CD4+ T-cell stimulation capacity and migration rate of dendritic cells that had phagocytosed tumor-associated antigens into tumor-draining lymph nodes, suggesting a positive impact on GM-CSF–sensitized innate immunity. Furthermore, KO/WGM mice displayed activated adaptive immunity by attenuating regulatory CD4+ T subsets and increasing numbers of Th17 and memory CD44hiCD4+ T subsets, both of which elicited superior antitumor effects as evidenced by adoptive cell transfer. In vivo depletion assays also revealed that CD4+ T cells were the main effectors of the persistent antitumor immunity. Our data collectively underscore a negative role of LTB4/BLT1 signaling in effective generation and maintenance of GM-CSF–induced antitumor memory CD4+ T cells.

    DOI: 10.1182/blood-2011-10-383240

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  • A high-affinity monoclonal antibody against the FLAG tag useful for G-protein-coupled receptor study Reviewed

    Fumiyuki Sasaki, Toshiaki Okuno, Kazuko Saeki, Liu Min, Naoya Onohara, Haruyasu Kato, Takao Shimizu, Takehiko Yokomizo

    Analytical Biochemistry   425 ( 2 )   157 - 165   2012.6

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

    DOI: 10.1016/j.ab.2012.03.014

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  • Antiproliferative activity of extracts prepared from three species of Reishi on cultured human normal and tumor cell lines Reviewed

    Yohtaro Katagata, Fumiyuki Sasaki

    Molecular Medicine Reports   3 ( 1 )   2009.11

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Spandidos Publications  

    DOI: 10.3892/mmr_00000237

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  • Studies on levels of polyphenolic compounds in commercial tea beverages, their free radical scavenging activities, and antioxidant activity of procyanidins Reviewed

    Sasaki Fumiyuki, Ishikawa Eri, Osari Suguru, Sato Reiko, Takemoto Naritaka, Honda Shinya, Fujikane Youichi, Suzuki Takashi, Osada Kyoichi

    Bulletin of the Faculty of Agriculture and Life Science, Hirosaki University   8   24 - 28   2005.12

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    Other Link: http://nature.cc.hirosaki-u.ac.jp/kohou2/bulletin/No_8.pdf

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Books

  • Bioactive lipid mediators : current reviews and protocols

    横溝, 岳彦, 村上, 誠( Role: ContributorChapter 29. A Novel Anti-FLAG Monoclonal Antibody Is Useful to Study GPCRs)

    Springer  2015.11  ( ISBN:4431556680

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    Total pages:426   Language:English  

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Misc.

  • The regulation of RANKL by mechanical force Reviewed

    Fumiyuki Sasaki, Mikihito Hayashi, Takehito Ono, Tomoki Nakashima

    Journal of Bone and Mineral Metabolism   39 ( 1 )   34 - 44   2021.1

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    Authorship:Lead author   Language:English   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:Springer Science and Business Media LLC  

    DOI: 10.1007/s00774-020-01145-7

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    Other Link: https://link.springer.com/article/10.1007/s00774-020-01145-7/fulltext.html

  • オメガ3脂肪酸経口摂取の加齢黄斑変性マウスモデルに対する効果の検証 Reviewed

    足立 啓介, 平形 寿彬, 佐々木 文之, 佐伯 和子, 李 賢哲, 松田 彰, 村上 晶, 横溝 岳彦

    日本眼科学会雑誌   124   192 - 194   2020.3

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  • The leukotriene receptors as therapeutic targets of inflammatory diseases Reviewed International journal

    Fumiyuki Sasaki, Takehiko Yokomizo

    International Immunology   31 ( 9 )   607 - 615   2019.8

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    Authorship:Lead author   Language:English   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:Oxford University Press (OUP)  

    <title>Abstract</title>
    Leukotrienes (LTs) are inflammatory mediators derived from arachidonic acid. LTs include the di-hydroxy acid LT (LTB4) and the cysteinyl LTs (CysLTs; LTC4, LTD4 and LTE4), all of which are involved in both acute and chronic inflammation. We and other groups identified a high-affinity LTB4 receptor, BLT1; the LTC4 and LTD4 receptors, CysLT1 and CysLT2; and the LTE4 receptor, GPR99. Pharmacological studies have shown that BLT1 signaling stimulates degranulation, chemotaxis and phagocytosis of neutrophils, whereas CysLT1 and CysLT2 signaling induces airway inflammation by increasing vascular permeability and the contraction of bronchial smooth muscle. Recently, we and other groups suggested that the LTB4–BLT1 axis and the cysteinyl LTs–CysLT1/2 axis are involved in chronic inflammatory diseases including asthma, atopic dermatitis, psoriasis, atherosclerosis, arthritis, obesity, cancer and age-related macular degeneration using animal models for disease and gene knockout mice. This review describes the classical and novel functions of LTs and their receptors in several inflammatory diseases and discusses the potential clinical applications of antagonists for LT receptors and inhibitors of LT biosynthesis.

    DOI: 10.1093/intimm/dxz044

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    Other Link: http://academic.oup.com/intimm/article-pdf/31/9/607/29203631/dxz044.pdf

  • ロイコトリエンB4第一受容体は滲出型加齢黄斑変性症の新規治療標的となる Invited

    佐々木文之, 横溝岳彦

    実験医学   37 ( 3 )   2019.2

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  • ロイコトリエンB4第一受容体BLT1による免疫活性化機構の解析

    古賀 友紹, 佐々木 文之, 佐伯 和子, 奥野 利明, 中尾 光善, 横溝 岳彦

    生命科学系学会合同年次大会   2017.12

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  • HMGB1及びLPSに誘導される炎症を抑制する新規低分子化合物の創製

    中島 槙吾, 玉田 賢弥, 佐藤 聡, 吉森 篤史, 市木 貴子, 佐々木 文之, 横溝 岳彦, 田沼 靖一

    日本生化学会大会プログラム・講演要旨集   89   2016.9

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  • HMGB1/RAGE相互作用を阻害する新規低分子化合物の創製

    89   2016.9

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  • 新規樹状細胞サブセットマーカー分子としてのBLT1受容体

    古賀友紹, 佐々木文之, 佐伯和子, 奥野利明, 横溝岳彦

    脂質生化学研究   55   123 - 124   2013.5

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  • 加齢黄斑変性におけるROCKアイソフォーム特異的macrophage education therapy

    中尾新太郎, ZANDI Souska, 石川桂二郎, 吉田茂生, 佐々木文之, 横溝岳彦, HAFEZI‐MOGHADAM Ali, 石橋達朗

    日本血管生物医学会学術集会プログラム・抄録集   21   122   2013

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    Language:Japanese  

    J-GLOBAL

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  • 新規抗FLAG抗体2H8の活用法 既存抗体との親和性、特異性、認識能の比較 Invited

    佐々木文之, 横溝岳彦

    実験医学   30 ( 8 )   2987 - 2992   2012.11

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

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  • LTB4シグナルの阻害はGM-CSF遺伝子による抗腫瘍効果の維持に関与する

    鍋田 春花, 井上 博之, 伊賀 睦了, 横田 洋介, 栗田 良, 佐々木 文之, 高山 浩一, 中西 洋一, 横溝 岳彦, 谷 憲三朗

    臨床血液   49 ( 9 )   1099 - 1099   2008.9

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    Language:Japanese   Publisher:(一社)日本血液学会-東京事務局  

    J-GLOBAL

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  • RANKL biology: bone metabolism, the immune system, and beyond Reviewed

    Takehito Ono, Mikihito Hayashi, Fumiyuki Sasaki, Tomoki Nakashima

    Inflammation and Regeneration   40 ( 1 )   2020.12

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    Language:English   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:Springer Science and Business Media LLC  

    <title>Abstract</title>Receptor activator of NF-κB (RANK) ligand (RANKL) induces the differentiation of monocyte/macrophage–lineage cells into the bone–resorbing cells called osteoclasts. Because abnormalities in RANKL, its signaling receptor RANK, or decoy receptor osteoprotegerin (OPG) lead to bone diseases such as osteopetrosis, the RANKL/RANK/OPG system is essential for bone resorption. RANKL was first discovered as a T cell-derived activator of dendritic cells (DCs) and has many functions in the immune system, including organogenesis, cellular development. The essentiality of RANKL in the bone and the immune systems lies at the root of the field of “osteoimmunology.” Furthermore, this cytokine functions beyond the domains of bone metabolism and the immune system, e.g., mammary gland and hair follicle formation, body temperature regulation, muscle metabolism, and tumor development. In this review, we will summarize the current understanding of the functions of the RANKL/RANK/OPG system in biological processes.

    DOI: 10.1186/s41232-019-0111-3

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    Other Link: http://link.springer.com/article/10.1186/s41232-019-0111-3/fulltext.html

  • Generation of monoclonal antibodies specific for mouse leukotriene B4 receptor 1 and N-terminal FLAG sequence

    Fumiyuki Sasaki, Kazuko Saeki, Toshiaki Okuno, Takehiko Yokomizo

    FASEB JOURNAL   25   2011.4

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    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:FEDERATION AMER SOC EXP BIOL  

    Web of Science

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  • BLOCKING OF THE LTB4 SIGNALING MAINTAINS THE IN VIVO ANTITUMOR EFFECTS OF GM-CSF TRANSDUCED TUMOR CELLS

    Yosuke Yokota, Haruka Nabeta, Hiroyuki Inoue, Mutsunori Iga, Meng Xin, Ryo Kurita, Fumiyuki Sasaki, Koichi Takayama, Yoichi Nakanishi, Takehiko Yokomizo, Kenzaburo Tani

    JOURNAL OF GENE MEDICINE   11 ( 12 )   1172 - 1172   2009.12

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    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:JOHN WILEY & SONS LTD  

    Web of Science

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Presentations

  • Sphingosine-1-phosphate lyase SGPL1 is required for NLRP3 inflammasome activation via the dynamic organization of endoplasmic reticulum and microtubules

    Fumiyuki Sasaki, Masumi Shimizu, Rimpei Morita

    2024.1 

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    Event date: 2024.1

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  • スフィンゴシン1リン酸分解酵素は小胞体-微小管ダイナミクスの制御を介してNLRP3インフラマソームの活性化を促進する

    佐々木文之, 清水真澄, 森田林平

    第96回日本生化学会大会, 福岡  2023.11 

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    Event date: 2023.10 - 2023.11

    Language:Japanese   Presentation type:Poster presentation  

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  • Sphingosine-1-phosphate lyase promotes NLRP3 inflammasome activation via the development of endoplasmic reticulum and microtubules

    Fumiyuki Sasaki, Masumi Shimizu, Rimpei Morita

    Keystone Symposia, Innate Immunity: From Innate Sensing to Adaptive Responses, US, UT, Snowbird  2023.4 

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    Event date: 2023.4

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  • Sphingosine-1-phosphate lyase promotes inflammasome activation via the development of endoplasmic reticulum network

    Fumiyuki Sasaki, Masumi Shimizu, Rimpei Morita

    2022.12 

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    Event date: 2022.12

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  • Generation and Characterization of high-affinity anti-FLAG monoclonal antibody that is useful to detect GPCRs

    Fumiyuki Sasaki, Naoya Onohara, Toshiaki Okuno, Takehiko Yokomizo

    4th International Conference on Phospholipase A2 and Lipid Mediators (PLM2009), Tokyo  2009.5 

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  • ロイコトリエンB4受容体とM1/M2マクロファージ

    佐々木文之, 古賀友紹, 佐伯和子, 奥野利明, 横溝岳彦

    自然炎症・脂質マシナリー合同若手ワークショップ, 徳島  2013.7 

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    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

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  • Leukotriene B4 receptor 1 signaling promotes neovascular age-related macular degeneration

    Keystone Symposia on Molecular and Cellular Biology, Montreal  2015.3 

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  • 骨メカニカルストレス受容機構の解明を目指して

    佐々木文之, 林幹人, 中島友紀

    第5回日本骨免疫学会, 沖縄  2019.6 

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  • ロイコトリエンB4産生経路およびロイコトリエンB4受容体BLT1は滲出型加齢黄斑変性症の新規治療標的となる(口頭発表)

    2019.7 

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  • The physiological function of a leukotriene B4 receptor 1 in M2 macrophages,

    Fumiyuki Sasaki, Tomoaki Koga, Kazuko Saeki, Toshiaki Okuno T, Takehiko Yokomizo

    2013 FASEB Summer Research Conference, Hokkaido  2013.8 

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  • Leukotriene B4 receptor 1 signaling promotes neovascular age-related macular degeneration

    Fumiyuki Sasaki, Tomoaki Koga, Kazuko Saeki, Toshiaki Okuno T, Takehiko Yokomizo

    The 43th Annual Meeting of the Japanese Society for Immunology, Kyoto  2014.12 

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  • M2 macrophages promote neovascular degeneration through the activation of the leukotriene B4 receptor 1 signaling

    Fumiyuki Sasaki, Tomoaki Koga, Kazuko Saeki, Toshiaki Okuno T, Takehiko Yokomizo

    6th International Conference on Phospholipase A2 and Lipid Mediators (PLM2015) from bench to translational medicine, Tokyo  2015.2 

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  • Expression and function of a leukotriene B4 receptor 1 in M2-type macrophage

    Fumiyuki Sasaki, Tomoaki Koga, Kazuko Saeki, Toshiaki Okuno, Takehiko Yokomizo

    2012.12 

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  • Generation of high-affinity monoclonal antibodies for G-protein coupled receptors study

    Fumiyuki Sasaki, Toshiaki Okuno, Takehiko Yokomizo

    The Annual Molecular Biology Institute Lake Arrowhead Retreat, USA, LA  2009.10 

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  • Generation of monoclonal antibodies specific for mouse leukotriene B4 receptor 1 and N-terminal FLAG sequence

    Fumiyuki Sasaki, Kazuko Saeki, Toshiaki Okuno T, Takehiko Yokomizo

    Experimental biology 2011 (ASBMB), USA, Washington D.C.  2011.4 

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  • GPCRの免疫沈降に有用な新規抗FLAG抗体の樹立と本抗体を用いた新規GPCR結合タンパク質の探索

    佐々木文之, 奥野利明, 佐伯和子, 横溝岳彦

    第84回日本生化学会, 京都  2011.9 

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  • Expression of an LTB4 Receptor BLT1 in M2 Macrophage

    Fumiyuki Sasaki, Tomoaki Koga, Kazuko Saeki, Toshiaki Okuno T, Takehiko Yokomizo

    The 10th JBS Biofrontier Symposium, Fukuoka  2011.11 

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  • BLT1発現が規定するマクロファージサブセットの解析

    佐々木文之, 古賀友紹, 佐伯和子, 奥野利明, 横溝岳彦

    第9回東京呼吸器リサーチフォーラム, 東京  2012.11 

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  • Generation and characterization of a high-affinity monoclonal antibody for mouse leukotriene B4 receptor 1 (BLT1)

    Fumiyuki Sasaki, Takehiko Yokomizo

    第82回日本生化学会, 兵庫  2009.10 

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  • Generation of high-affinity monoclonal antibodies useful for G-protein coupled receptors

    Fumiyuki Sasaki, Toshiaki Okuno T, Kazuko Saeki, Takehiko Yokomizo

    The 6th Japan-Korea Conference on Cellular Signaling for Young Scientists  2009.11 

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  • Generation and Characterization of high-affinity anti-FLAG monoclonal antibody that is useful to detect GPCRs

    Fumiyuki Sasaki F, Naoya Onohara, Toshiaki Okuno, Takehiko Yokomizo

    The 4th Global COE International Symposium 2009 joint with the 19th Hot Spring Harbor Symposium  2009.11 

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  • Establishment of a novel monoclonal antibody, 7A8, which specifically recognizes mouse granulocytes and monocytes expressing leukotriene B4 receptor

    Fumiyuki Sasaki, Takehiko Yokomizo

    第83回日本生化学会・第33回分子生物学会合同大会, 兵庫  2010.12 

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  • Generation of monoclonal antibody for mouse leukotriene B4 receptor 1

    Fumiyuki Sasaki, Kazuko Saeki, Toshiaki Okuno T, Takehiko Yokomizo

    7th Global-COE International Symposium and 6th Young Investigators Forum, Singapore  2009.10 

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  • Generation and characterization of a novel high-affinity monoclonal antibody for FLAG tag

    Fumiyuki Sasaki, Naoya Onohara, Toshiaki Okuno, Takehiko Yokomizo

    第31回日本分子生物学会年会・第81回日本生化学会合同大会, 兵庫  2008.12 

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  • A high-affinity monoclonal antibody against the FLAG tag useful for G-protein coupled receptor study

    Fumiyuki Sasaki, Takehiko Yokomizo

    BIT’s 5 th Annual International Congress of Antibodies-2013, China  2013.5 

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  • ロイコトリエンB4産生経路およびロイコトリエンB4受容体BLT1は滲出型加齢黄斑変性症の新規治療標的となる(ポスター発表)

    佐々木文之, 古賀友紹, 横溝岳彦

    第40回日本炎症・再生医学会, 神戸  2019.7 

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  • Generation of chimeric high-affinity monoclonal antibodies against mouse leukotriene B4 receptor 1 and DYKDDDDK peptide

    Fumiyuki Sasaki, Koki Ikeda, Ayumi Ueno, Kazuko Saeki, Tomoaki Koga, Takehiko Yokomizo

    第86回日本生化学会合同大会, 横浜  2013.9 

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  • 新規高親和性抗FLAG単クローン抗体の作製とその有用性の検討(ポスター発表)

    佐々木文之, 小野原直哉, 奥野利明, 横溝岳彦

    平成21年度日本生化学会九州支部例会(福岡大会), 福岡  2009.5 

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  • 新規抗FLAG単クローン抗体の評価

    佐々木文之, 横溝岳彦

    第2回グローバルCOE若手研究者発表会・11回九州大学生体防御医学研究所リトリート, 熊本  2008.9 

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  • 新規高親和性抗FLAG単クローン抗体の作製とその有用性の検討(口頭発表)

    2009.5 

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Industrial property rights

  • 加齢黄斑変性症予防治療剤

    佐々木 文之, 横溝 岳彦

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    Applicant:学校法人順天堂

    Application no:特願JP2014-228828  Date applied:2014.11

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Awards

  • 2022年度 公益財団法人 今井精一記念財団 研究助成 採択

    2023.11  

    佐々木文之(研究代表者)

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  • 2023年度 日本免疫学会 Tadamitsu Kishimoto International Travel Award 受賞

    2023.3  

    佐々木 文之

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  • The 51st Annual Meeting of the Japanese Society for Immunology Best Poster Award

    2022.12   Sphingosine-1-phosphate lyase promotes inflammasome activation via the development of endoplasmic reticulum network

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  • 2022年度 公益財団法人 持田記念医学薬学振興財団 研究助成 採択

    2022.9  

    佐々木文之(研究代表者)

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  • 研究助成

    2021.12   神澤医学研究振興財団  

    佐々木文之(研究代表者), 根岸靖幸(共同研究者)

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  • 丸山記念研究助成金

    2021.9   日本医科大学  

    佐々木文之(研究代表者)

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  • The 40th Annual Meeting of the Japanese Society of Inflammation and Regeneration Best Presentation Award

    2019.7  

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  • 戦略的クラスター形成パイロット事業 プロジェクト採択

    2018.6   公益財団法人大田区産業振興協会  

    白石利治(研究代表者), 安達泰治(共同研究者), 佐々木文之(共同研究者)

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Research Projects

  • Identification and functional analysis of a novel skeletal muscle-specific mechanical stress receptor in controlling the inflammatory and immune responses

    2022.4 - 2027.3

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

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  • エンドサイトーシスによるNLRP3インフラマソーム形成制御機構と生理的意義の解明

    2022.4 - 2025.3

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

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    Authorship:Coinvestigator(s) 

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  • Identification of an osteocyte-specific mechanical stress receptor by the novel screening method

    Grant number:19K18452  2019.4 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research (KAKENHI), Grant-in-Aid for Early-Career Scientists  Grant-in-Aid for Early-Career Scientists

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    Authorship:Principal investigator 

    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

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Other research activities

  • 第38回日本医科大学医学教育のためのFDワークショップ

    2021.6

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Media Coverage

  • 「加齢黄斑変性症 仕組み解明」 順天堂大 目に異常な血管形成 Newspaper, magazine

    日刊工業新聞  2016.10

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