Updated on 2024/06/10

Information

 

写真a

 
KUNIMURA KAZUFUMI
 
Organization
Medical Institute of Bioregulation Department of Immunobiology and Neuroscience Assistant Professor
Title
Assistant Professor
Tel
0926426828
Homepage
External link

Degree

  • M.D.

  • Ph.D.

Research History

  • 株式会社 麻生 飯塚病院 (初期研修医)

    株式会社 麻生 飯塚病院 (初期研修医)

Research Interests・Research Keywords

  • Research theme:Development of novel drugs for atopic dermatitis

    Keyword:Atopic dermatitis, IL-31, Academia drug discovery

    Research period: 2020.4

  • Research theme:Fetomaternal immune cross-talk

    Keyword:Pregnancy, Allergy

    Research period: 2019.4

Awards

  • 第23回 生医研リトリート 優秀口演賞

    2021.7   九州大学 生体防御医学研究所   口演発表における投票制度による受賞

  • 第21回生医研リトリート 優秀口演賞

    2018.8   九州大学 生体防御医学研究所  

  • 医学部博士課程奨学助成

    2015.4   武田科学振興財団  

  • Intelligence of the Year 2014

    2015.3   Intelligence of the Year 2014

Papers

  • Cholesterol sulfate limits neutrophil recruitment and gut inflammation during mucosal injury Reviewed

    Kenji Morino*, Kazufumi Kunimura*, Yuki Sugiura, Yoshihiro Izumi, Keisuke Matsubara, Sayaka Akiyoshi, Rei Maeda, Kenichiro Hirotani, Daiji Sakata, Seiya Mizuno, Satoru Takahashi, Takeshi Bamba, Takehito Uruno, Yoshinori Fukui

    Frontiers in Immunology   2023.3

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

    DOI: 10.3389/fimmu.2023.1131146

  • DOCK2 regulates MRGPRX2/B2-mediated mast cell degranulation and drug-induced anaphylaxis Reviewed

    Kazufumi Kunimura, Sayaka Akiyoshi, Takehito Uruno, Keisuke Matsubara, Daiji Sakata, Kenji Morino, Kenichiro Hirotani, Yoshinori Fukui

    The Journal of Allergy and Clinical Immunology   2023.2

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

    DOI: 10.1016/j.jaci.2023.01.029

  • Identification of a functional DOCK8 gene polymorphism associated with atopic dermatitis Reviewed International journal

    Kazufumi Kunimura, Kazuhiko Yamamura, Takeshi Nakahara, Makiko Kido-Nakahara, Takehito Uruno, Yoshinori Fukui

    Allergy   2022.7

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

    DOI: 10.1111/all.15429

  • DOCK8 deficiency causes a skewing to type 2 immunity in the gut with expansion of group 2 innate lymphoid cells Reviewed International journal

    Keisuke Matsubara*, Kazufumi Kunimura*, Nana Yamane, Ryosuke Aihara, Tetsuya Sakurai, Daiji Sakata, Takehito Uruno, Yoshinori Fukui

    Biochemical and Biophysical Research Communications   559   135 - 140   2021.6

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

    DOI: 10.1016/j.bbrc.2021.04.094

  • DOCK8 controls survival of group 3 innate lymphoid cells in the gut through Cdc42 activation. Reviewed International journal

    Ryosuke Aihara*, Kazufumi Kunimura*, Mayuki Watanabe, Takehito Uruno, Nana Yamane, Tetsuya Sakurai, Daiji Sakata, Fusanori Nishimura, Yoshinori Fukui

    International Immunology   33 ( 3 )   149 - 160   2020.9

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

    DOI: 10.1093/intimm/dxaa066

    Repository Public URL: http://hdl.handle.net/2324/4495853

  • S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer's Patches. Reviewed International journal

    Cell reports   29 ( 9 )   2823 - 2834   2019.11

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

    DOI: 10.1016/j.celrep.2019.10.091

  • Altered macrophage phenotypes in a case of autoimmune pulmonary alveolar proteinosis Reviewed

    Kentaro Hata, Toyoshi Yanagihara, Keisuke Matsubara, Kazufumi Kunimura, Daisuke Eto, Kunihiro Suzuki, Kazuya Tsubouchi, Satoshi Ikegame, Yoshinori Fukui, Isamu Okamoto

    ERJ Open Research   00500 - 2023   2023.9

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

    DOI: 10.1183/23120541.00500-2023

  • A case of high-grade VUE diagnosed by additional immunostaining rather than H&E staining alone

    Kenichiro Hirotani, Kazufumi Kunimura, Takeshi Iwasaki, Yoshinori Fukui, Kiyoko Kato

    Placenta   141   94 - 94   2023.9

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    Language:English  

    DOI: 10.1016/j.placenta.2023.08.053

  • Mass cytometry analysis of B-cell populations in extranodal marginal-zone lymphoma of mucosa-associated lymphoid tissue of the lung Reviewed

    Toyoshi Yanagihara, Kentaro Hata, Keisuke Matsubara, Kazufumi Kunimura, Kunihiro Suzuki, Kazuya Tsubouchi, Satoshi Ikegame, Yoshihiro Baba, Yoshinori Fukui, Isamu Okamoto

    Annals of Hematology   2023.7

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

    DOI: 10.1007/s00277-023-05391-3

  • Exploratory mass cytometry analysis reveals immunophenotypes of cancer treatment-related pneumonitis Reviewed International journal

    Toyoshi Yanagihara, Kentaro Hata, Keisuke Matsubara, Kazufumi Kunimura, Kunihiro Suzuki, Kazuya Tsubouchi, Satoshi Ikegame, Yoshihiro Baba, Yoshinori Fukui, Isamu Okamoto

    eLife   12 ( RP87288 )   2023.6

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

    DOI: 10.7554/elife.87288.1

  • Mass cytometry identifies characteristic immune cell subsets in bronchoalveolar lavage fluid from interstitial lung diseases Reviewed

    Kentaro Hata, Toyoshi Yanagihara, Keisuke Matsubara, Kazufumi Kunimura, Kunihiro Suzuki, Kazuya Tsubouchi, Daisuke Eto, Hiroyuki Ando, Maki Uehara, Satoshi Ikegame, Yoshihiro Baba, Yoshinori Fukui, Isamu Okamoto

    Frontiers in Immunology   14   1145814   2023.3

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

    DOI: 10.3389/fimmu.2023.1145814

  • Expansion of ST2-expressing macrophages in a patient with bronchiolitis obliterans syndrome Reviewed

    Toyoshi Yanagihara, Kentaro Hata, Kunihiro Suzuki, Keisuke Matsubara, Kazufumi Kunimura, Kazuya Tsubouchi, Daisuke Eto, Hiroyuki Ando, Maki Uehara, Satoshi Ikegame, Yoshinori Fukui, Isamu Okamoto

    ERJ Open Research   2023.3

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

    DOI: 10.1183/23120541.00033-2023

  • Pharmacological intervention of cholesterol sulfate-mediated T cell exclusion promotes antitumor immunity Reviewed

    Takaaki Tatsuguchi, Takehito Uruno, Yuki Sugiura, Kounosuke Oisaki, Daisuke Takaya, Daiji Sakata, Yoshihiro Izumi, Takaya Togo, Yuko Hattori, Kazufumi Kunimura, Testuya Sakurai, Teruki Honma, Takeshi Bamba, Masafumi Nakamura, Motomu Kanai, Makoto Suematsu, Yoshinori Fukui

    Biochemical and Biophysical Research Communications   609   183 - 188   2022.4

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

    DOI: 10.1016/j.bbrc.2022.04.035

  • Cancer-derived cholesterol sulfate is a key mediator to prevent tumor infiltration by effector T cells Reviewed

    Takaaki Tatsuguchi, Takehito Uruno, Yuki Sugiura, Daiji Sakata, Yoshihiro Izumi, Tetsuya Sakurai, Yuko Hattori, Eiji Oki, Naoto Kubota, Koshiro Nishimoto, Masafumi Oyama, Kazufumi Kunimura, Takuto Ohki, Takeshi Bamba, Hideaki Tahara, Michiie Sakamoto, Masafumi Nakamura, Makoto Suematsu, Yoshinori Fukui

    International Immunology   2022.1

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

    DOI: 10.1093/intimm/dxac002

  • The molecular basis for IL-31 production and IL-31-mediated itch transmission: from biology to drug development Invited Reviewed International journal

    Kazufumi Kunimura, Yoshinori Fukui

    International Immunology   2021.9

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

    DOI: 10.1093/intimm/dxab065

  • Targeted inhibition of EPAS1–driven IL-31 production by a small-molecule compound Reviewed International journal

    148 ( 2 )   633 - 638   2021.4

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

    Background
    IL-31 is a major pruritogen associated with atopic dermatitis (AD). Although a specific antibody for IL-31 receptor has been shown to alleviate pruritus in patients with AD, therapeutic approaches to inhibition of IL-31 production remain unexploited. IL-31 production by Th cells critically depends on the transcription factor EPAS1, which mediates IL31 promoter activation in collaboration with SP1.

    Objective
    We aimed at developing small-molecule inhibitors that selectively block IL-31 production by Th cells.

    Methods
    We generated the reporter cell line that inducibly expressed EPAS1 in the presence of doxycycline to mediate Il31 promoter activation, and we screened 9600 chemical compounds. The selected compounds were further examined by using Th cells from a spontaneous mouse model of AD and Th cells from patients with AD.

    Results
    We have identified 4-(2-(4-isopropylbenzylidene)hydrazineyl)benzoic acid (IPHBA) as an inhibitor of IL31 induction. Although IPHBA did not affect nonspecific T-cell proliferation, IPHBA inhibited antigen-induced IL-31 production by Th cells from both an AD mouse model and patients with AD without affecting other cytokine production and hypoxic responses. In line with this, itch responses induced by adoptive transfer of IL-31–producing Th cells were attenuated when mice were orally treated with IPHBA. Mechanistically, IPHBA inhibited the association between EPAS1 and SP1, resulting in defective recruitment of both transcription factors to the specific sites of the IL31 promoter. We also determined the structure-activity relationship of IPHBA by synthesizing and analyzing 201 analogous compounds.

    Conclusion
    IPHBA could be a potential drug leading to inhibition of EPAS1-driven IL-31 production.

    DOI: 10.1016/j.jaci.2021.03.029

  • A conserved PI(4,5)P2–binding domain is critical for immune regulatory function of DOCK8 Reviewed International journal

    4 ( 4 )   e202000873   2021.2

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

    DOCK8 is a Cdc42-specific guanine-nucleotide exchange factor that is essential for the development and functions of various subsets of leukocytes in innate and acquired immune responses. Although DOCK8 plays a critical role in the spatial control of Cdc42 activity during interstitial leukocyte migration, the mechanism remains unclear. We show that the DOCK homology region (DHR)-1 domain of DOCK8 binds specifically to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and is required for its recruitment to the plasma membrane. Structural and biochemical analyses reveal that DOCK8 DHR-1 domain consists of a C2 domain-like core with loops creating the upper surface pocket, where three basic residues are located for stereospecific recognition of phosphoinositides. Substitution of the two basic residues, K576 and R581, with alanine abolished PI(4,5)P2 binding in vitro, ablated the ability of DOCK8 to activate Cdc42 and support leukocyte migration in three-dimensional collagen gels. Dendritic cells carrying the mutation exhibited defective interstitial migration in vivo. Thus, our study uncovers a critical role of DOCK8 in coupling PI(4,5)P2 signaling with Cdc42 activation for immune regulation.

    DOI: 10.26508/lsa.202000873

  • Selective role of neurokinin B in IL-31-induced itch response in mice. Reviewed International journal

    Daiji Sakata, Takehito Uruno, Keisuke Matsubara, Tsugunobu Andoh, Kazuhiko Yamamura, Yuki Magoshi, Kazufumi Kunimura, Yasuhisa Kamikaseda, Masutaka Furue, Yoshinori Fukui

    The Journal of allergy and clinical immunology   144 ( 4 )   1130 - 1133   2019.10

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

    DOI: 10.1016/j.jaci.2019.06.031

  • The Rac Activator DOCK2 Mediates Plasma Cell Differentiation and IgG Antibody Production. Reviewed International journal

    Miho Ushijima, Takehito Uruno, Akihiko Nishikimi, Fumiyuki Sanematsu, Yasuhisa Kamikaseda, Kazufumi Kunimura, Daiji Sakata, Takaharu Okada, Yoshinori Fukui

    Frontiers in immunology   9   243 - 243   2018.2

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

    DOI: 10.3389/fimmu.2018.00243

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Presentations

  • アトピー性皮膚炎に関わる機能的なDOCK8遺伝子多型の同定

    國村 和史, 福井 宣規

    第52回日本免疫学会学術集会  2024.1 

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    Event date: 2024.1

    Language:English  

    Country:Other  

  • 免疫細胞の遊走抑制能を有した ”腸粘膜メタボライト”による新たな炎症収束機構 Invited

    國村 和史

    CyTOFプロフェッショナルウェビナー  2023.12 

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    Event date: 2023.12

    Language:Others  

    Country:Other  

  • DOCK2/DOCK8分子を介した多彩な免疫制御メカニズム Invited

    國村 和史, 宇留野 武人, 福井 宣規

    第96回日本生化学会大会  2023.10 

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    Event date: 2023.10 - 2023.11

    Language:English  

    Country:Other  

  • DOCK2は肥満細胞のMRGPRX2/B2介在性脱顆粒と薬剤誘発性アナフィラキシーを制御する Invited

    國村 和史

    第18回生命医科学研究所ネットワーク国際シンポジウム  2023.10 

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    Event date: 2023.10

    Language:English  

    Country:Other  

  • 薬剤性アナフィラキシーに関わるMRGPRB2/X2受容体のシグナル経路の解明

    國村 和史

    第51回日本免疫学会学術集会  2022.12 

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    Event date: 2022.12

    Language:English  

    Country:Other  

  • 免疫組織染色により診断し得たhigh-grade VUE (Villitis of Unknown Etiology) の一例

    廣谷 賢一郎, 國村 和史, 岩崎 健, 福井 宣規, 加藤 聖子

    第31回日本胎盤学会学術集会  2023.11 

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    Event date: 2023.11

    Language:Others  

    Country:Other  

  • 母体−胎児間インターフェイスにおける免疫特権環境形成メカニズムの解明

    國村 和史

    第32回Kyoto T Cell Conference (KTCC)  2023.6 

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    Event date: 2023.6

    Language:English  

    Country:Other  

  • コレステロール硫酸は白血球の遊走制御を介して眼の免疫特権環境の形成に寄与する Invited

    國村和史

    第95回日本生化学会大会  2022.11 

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    Event date: 2022.11

    Language:Others  

    Country:Other  

  • 腫瘍によるコレステロール硫酸を介した免疫回避機構の発見

    國村 和史

    第31回Kyoto T Cell Conference (KTCC)  2022.5 

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    Event date: 2022.5

    Language:Japanese  

    Country:Other  

  • アトピー性皮膚炎におけるEPAS1誘導性IL-31産生を抑制する低分子化合物の開発

    國村 和史

    第30回ホットスプリングハーバー国際シンポジウム  2022.1 

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    Event date: 2022.1

    Language:English  

    Country:Other  

  • EPAS1によって誘導されるIL-31産生を選択的に阻害する低分子化合物の発見

    國村 和史

    第50回日本免疫学会学術集会  2021.12 

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    Event date: 2021.12

    Language:English  

    Country:Other  

  • IL-31の産生制御機構および痒みの伝達機構: バイオロジーから創薬へ Invited

    國村 和史

    第16回生命医科学研究所ネットワーク国際シンポジウム  2021.11 

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    Event date: 2021.11

    Language:English  

    Country:Other  

  • アトピー性皮膚炎におけるEPAS1誘導性IL-31産生を抑制する低分子化合物の開発

    國村 和史

    第70回日本アレルギー学会学術大会  2021.10 

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    Event date: 2021.10

    Language:Japanese  

    Country:Other  

  • 小腸パイエル板のM細胞分化に不可欠な新規環境因子の同定 Invited

    國村和史

    第29回ホットスプリングハーバー国際シンポジウム  2020.2 

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    Event date: 2020.2

    Language:English  

    Country:Other  

  • 転写因子EPAS1はIL-31誘導を介してDOCK8欠損におけるアトピー性皮膚炎発症を惹起する

    國村和史

    米国免疫学会議  2019.5 

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    Event date: 2019.5

    Language:English  

    Country:Other  

  • DOCK8 欠損によるアトピー性皮膚炎発症の分子基盤:転写因子 EPAS1 を介した IL-31 産生の重要性

    國村和史

    欧州免疫学会議  2018.9 

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    Event date: 2018.9

    Language:English  

    Country:Other  

  • 腸管免疫システムにおけるDOCK8の新しい機能 Invited

    國村和史

    第4回プサン大学ー九州大学合同シンポジウム  2017.12 

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    Event date: 2017.12

    Language:English  

    Country:Other  

  • Rac GEFであるDOCKファミリーによる樹状細胞遊走の協調的制御機構

    國村和史

    国際免疫学会議  2016.8 

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    Event date: 2016.8

    Language:Others  

    Country:Other  

  • DVTを併発した後天性第V因子インヒビターの1例

    國村和史

    第305回日本内科学会九州地方会  2014.5 

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    Event date: 2014.5

    Language:Japanese  

    Country:Other  

  • Coordinate regulation of dendritic cell migration by the DOCK family of Rac guanine exchange factors

    K. Kunimura, Y. Fukui

    EUROPEAN JOURNAL OF IMMUNOLOGY  2016.8 

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    Language:English  

    Country:Australia  

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MISC

  • The molecular basis for IL-31 production and IL-31-mediated itch transmission: from biology to drug development Reviewed

    Kazufumi Kunimura, Yoshinori Fukui

    International Immunology   2021.9

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    Language:English   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

    DOI: 10.1093/intimm/dxab065

  • DOCK family proteins: key players in immune surveillance mechanisms. Reviewed

    Kazufumi Kunimura, Takehito Uruno, Yoshinori Fukui

    International immunology   2020.1

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    Language:English   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

    DOI: 10.1093/intimm/dxz067

  • 薬剤性アナフィラキシーに関わるMRGPRX2/B2受容体を介したマスト細胞の脱顆粒制御機構

    國村 和史

    月刊「臨床免疫・アレルギー科」   2023.12

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    Language:Japanese  

  • アトピー性皮膚炎におけるIL-31の産生制御機構

    國村 和史, 福井 宣規

    月刊「皮膚科」   2023.9

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    Language:Japanese  

  • 創薬標的としてのIL-31の分子基盤:DOCK8と転写因子EPAS1

    國村和史, 福井宣規

    月刊「臨床免疫・アレルギー科」   2022.3

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    Language:Japanese  

  • The transcription factor EPAS1 links DOCK8 deficiency to atopic skin inflammation via IL-31 induction

    Kazufumi Kunimura, Yoshinori Fukui

    The Journal of Immunology   2019.5

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    Language:English  

    DOI: 10.4049/jimmunol.202.supp.55.11

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Professional Memberships

  • Japanese Society for Immunology

  • Japanese Society of Allergology

  • Japan Society for DOHaD (Developmental Origins of Health and Disease)

Academic Activities

  • 準備・運営 International contribution

    第32回Hot Spring Harbor国際シンポジウム  ( 福岡 ) 2023.10

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    Type:Competition, symposium, etc. 

    Number of participants:200

  • 企画立案・運営等

    第24回免疫サマースクール2023 in 福岡  ( 福岡 ) 2023.8

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    Type:Competition, symposium, etc. 

    Number of participants:100

Research Projects

  • 母児間インターフェイスにおける免疫特権環境形成の分子基盤

    Grant number:23K15816  2023 - 2025

    日本学術振興会  科学研究費助成事業  若手研究

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • 妊娠成立・維持に働く胎児保護分子の実証と制御法開発

    2023 - 2025

    戦略的創造研究推進事業 (文部科学省)

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    Authorship:Principal investigator  Grant type:Contract research

  • IL-31産生阻害薬の開発に向けたEPAS1-SP1複合体の立体構造解明とリード化合物の創出

    2023 - 2025

    医学系研究助成(基礎)

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    Authorship:Principal investigator  Grant type:Contract research

  • 妊娠における胎盤由来脂質代謝産物の基礎および臨床的意義の検証

    2023

    2023年度 研究助成

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    Authorship:Principal investigator  Grant type:Contract research

  • 腸内細菌と免疫細胞を隔てる新規粘膜バリアに着目した炎症性腸疾患の病態解明

    2022

    一般財団法人 貝原守一医学振興財団 研究助成

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    Authorship:Principal investigator  Grant type:Contract research

  • 薬剤性アナフィラキシー克服を目指したマスト細胞の脱顆粒制御機構の解明

    Grant number:21K15472  2021 - 2022

    日本学術振興会  科学研究費助成事業  若手研究

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • 胎児-母体境界領域における免疫特権環境形成の分子基盤

    2021

    公益財団法人 神澤医学研究振興財団 2020年度(第24回)研究助成

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    Authorship:Principal investigator  Grant type:Contract research

  • 薬剤性アナフィラキシーの攻略を目指した分子基盤の解明

    2020

    QRプログラム(わかばチャレンジ)

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    Authorship:Principal investigator  Grant type:On-campus funds, funds, etc.

  • 胎児・母体免疫クロストークによる生体恒常性維持と疾患感受性決定の分子基盤

    2019.10 - 2025.3

    日本 

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    Authorship:Coinvestigator(s) 

    AMED-CREST: 早期ライフステージ

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FD Participation

  • 2024.3   Role:Participation   Title:医学部・医学系学府合同教育FD:大学病院の苦悩と医学研究の課題

    Organizer:[Undergraduate school/graduate school/graduate faculty]

  • 2022.4   Role:Participation   Title:令和4年度 第1回全学FD(新任教員の研修)The 1st All-University FD (training for new faculty members) in FY2022

    Organizer:University-wide

  • 2021.7   Role:Participation   Title:生体防御医学研究所FD

    Organizer:[Undergraduate school/graduate school/graduate faculty]

Media Coverage

  • 薬剤性アナフィラキシー制圧の鍵となる新しいシグナル経路を発見 ~ MRGPRX2 受容体が関わる様々なアレルギー疾患の制御に期待 ~

    2023.2

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