Takashi Izumi

Vice President(Research and Industry-Academia Collaboration)
Faculty of Health Care,Department of Acupuncture and MoxibustionDean of Faculty/Chair of Department/Professor
Graduate School of Health Sciences,Doctoral Program in Health SciencesDean of Graduate School/Chair of Program/Professor
Graduate School of Health Sciences,Master's and Doctoral Programs in Acupuncture and MoxibustionDean of Graduate School/Chair of Program/Professor
Last Updated :2025/10/07

■Researcher basic information

Degree

  • Doctor of Medicine, The University of Tokyo

Research Keyword

  • Biosensor
  • Analytical Chemistry
  • Biomarker
  • Mass spectrometry
  • Signal Transduction
  • Lipid Mediator

Field Of Study

  • Manufacturing technology (mechanical, electrical/electronic, chemical engineering), Electronic devices and equipment
  • Nanotechnology/Materials, Nano/micro-systems
  • Nanotechnology/Materials, Analytical chemistry
  • Life sciences, Medical systems
  • Life sciences, Functional biochemistry
  • Life sciences, Respiratory medicine
  • Life sciences, Pathobiochemistry
  • Life sciences, Medical biochemistry

■Career

Career

  • May 2025 - Present
    Teikyo Heisei University
  • Apr. 2021 - Present
    Teikyo Heisei University, Graduate School of Health Sciences, Dean
  • Apr. 2021 - Present
    Teikyo Heisei University, Vice President
  • Apr. 2019 - Present
    Teikyo Heisei University, Dean, Faculty of Health Care, Director, Department of Acupunture and Moxibustion
  • Apr. 2018 - Present
    Gunma University
  • Apr. 2018 - Present
    Gunma University
  • Apr. 2018 - Present
    Teikyo Heisei University, Faculty of Health Care, Professor
  • May 2021 - May 2025
    Teikyo Heisei University
  • Apr. 2021 - Mar. 2024
    Gunma University, Special Professor
  • Apr. 2018 - Mar. 2021
    Gunma University, Graduate School of Medicine, Appointed Professor
  • Apr. 2017 - Mar. 2018
    Gunma University, Vice President
  • Apr. 2003 - Mar. 2018
    Gunma University, Graduate School of Medicine, Professor
  • Apr. 2015 - Mar. 2017
    Gunma University
  • Apr. 2011 - Mar. 2015
    Gunma University, Faculty of Medicine, Dean
  • Apr. 2011 - Mar. 2015
    Gunma University, Graduate School of Medicine, Dean
  • Aug. 2000 - Mar. 2013
    Gunma University, Faculty of Medicine, Professor
  • Apr. 2009 - Mar. 2011
    Gunma University, Vice President
  • Oct. 2004 - Mar. 2008
    Waseda University
  • Apr. 1998 - Jul. 2000
    The University of Tokyo, Graduate School of Medicine, Assistant Professor
  • Apr. 1991 - Mar. 1998
    The University of Tokyo, Faculty of Medicine, Research Associate
  • Jun. 1990 - Mar. 1991
    The University of Tokyo, Faculty of Medicine, Researcher
  • Jul. 1987 - Jun. 1990
    Karolinska Institute, Sweden, Research Fellow
  • Jun. 1984 - Jun. 1987
    The University of Tokyo, Faculty of Medicine, Researcher
  • Jun. 1977 - May 1984
    The University of Tokyo Hospital, Medical Doctor

Educational Background

  • Apr. 1973 - Mar. 1977, The University of Tokyo, Faculty of Medicine, School of Medicine
  • Apr. 1971 - Mar. 1973, The University of Tokyo, College of Arts and Sciences

Member History

  • Jul. 2024 - Present
    Member of the ASBMB’s Lipid Research Division (LRD), American Society for Biochemistry and Molecular Biology (ASBMB)
  • Oct. 2004 - Present
  • Jan. 2001 - Present
  • Jan. 2000 - Present
  • Jan. 2011 - Jun. 2024
  • Sep. 2000 - Mar. 2018
  • Jan. 2016 - Dec. 2017
  • Jan. 2011 - Dec. 2016
  • Apr. 2011 - Mar. 2015
  • Jan. 2005 - Dec. 2010
  • Jun. 2010

■Research activity information

Award

  • Feb. 2024
    The Scientific Research Honor Society, USA, Full Member, Sigma Xi
    Scholarly achievements and contributions to the advancement of knowledge
    Takashi Izumi
  • Mar. 1978

Paper

MISC

Books and other publications

Lectures, oral presentations, etc.

  • Design and Development of Silicon Nanowire Biosensor with Enhanced Sensitivity and Specificity for Biomolecule Detection               
    Hui Zhang; Fumiya Osawa; Yawei Qiu; Haru Okamoto; Zhiheng Liu; Noriyasu Ohshima; Toshiya Sakata; Taira Kajisa; Takashi Izumi; Hayato Sone
    5th Gunma International Symposium 2025 (GIS2025), 23 Jan. 2025
  • Enhancing Detection Sensitivity of Si Nanowire Biosensor Through Controlled Channel Impurity Concentrations               
    Fumiya Osawa; Hui Zhang; Yawei Qiu; Noriyasu Ohshima; Toshiya Sakata; Taira Kajisa; Takashi Izumi; Hayato Sone
    5th Gunma International Symposium 2025 (GIS2025), 23 Jan. 2025
  • Si ナノワイヤバイオセンサの不純物濃度制御と電気特性評価               
    09 Dec. 2024
  • Si ナノワイヤバイオセンサ作製のための熱酸化によるSi 層膜厚制御               
    09 Dec. 2024
  • Si ナノワイヤバイオセンサ高感度化を目指した幅及び半導体極性効果の検証               
    09 Dec. 2024
  • Ultrasensitive Specific Detection of Anti-influenza A H1N1 Hemagglutinin Monoclonal Antibody Using Silicon Nanowire Field Effect Biosensors               
    Hui Zhang; Fumiya Osawa; Haru Okamoto; Yawei Qiu; Zhiheng Liu; Noriyasu Ohshima; Taira Kajisa; Toshiya Sakata; Takashi Izumi; Hayato Sone
    37th International Microprocesses and Nanotechnology Conference (MNC2024), 14 Nov. 2024
  • Challenges in Forming Sub-10 nm Nanowires via Directed Self-Assembly for Future Applications in Silicon Nanowire Biosensor               
    13 Nov. 2024
  • 分岐鎖アミノ酸代謝と細胞老化・個体老化の関係               
    Nov. 2024
  • COMSOL有限要素解析法を用いた高感度Siナノワイヤバイオセンサの最適な構造の予測               
    19 Sep. 2024
  • 分岐鎖アミノ酸代謝の変調が細胞老化及び個体老化に与える影響               
    15 Jun. 2024
  • The Possibility of Ultrasensitive Detection of Biomolecules using Silicon Nanowire Biosensor with Structural Optimization               
    16 Nov. 2023
  • テロメア短縮系を用いた効率的な複製老化系の樹立および分岐鎖アミノ酸代謝の細胞老化における役割の解析               
    31 Oct. 2023
  • 非接触型導電率検出キャピラリー電気泳動を用いた寒冷ストレス下における唾液イオンの網羅的解析               
    Nov. 2023
  • Siナノワイヤバイオセンサ電気特性と検出感度の幅及び極性依存性               
    21 Sep. 2023
  • Siナノワイヤバイオセンサ空乏領域の推測による高感度化要因の解明               
    21 Sep. 2023
  • 骨芽細胞様細胞株MC3T3-E1におけるPGE2分泌を介したメカノストレス伝播機構の解析               
    08 Jun. 2023
  • マウス由来GDE7は環状ホスファチジン酸を産生する酵素活性を有する               
    Jun. 2022
  • 高感度Siナノワイヤバイオセンサ作製のための最適なドーピング濃度の探求               
    16 Dec. 2021
  • 電子線描画法を用いた超高感度 Siナノワイヤバイオセンサの作製と特性評価               
    16 Dec. 2021
  • Development of rapid and efficient induction system for replicative senescence by mimicking telomere shortening               
    Yuma Aramaki; Kazuki Irie; Aiko Tsuchida; Takashi Izumi; Yoji A. Minamishima; Akimitsu Konishi
    14 Dec. 2021
  • 分岐鎖アミノ酸代謝の変調による細胞老化制御機構               
    Dec. 2021
  • 分岐鎖アミノ酸代謝の変調による細胞老化制御機構               
    19 Jun. 2021
  • MC3T3-E1における、脂質オートクライン刺激とエストラジオール刺激のクロストーク機構の解析               
    Dec. 2020
  • キャピラリー電気泳動を用いる唾液中の陰及び陽イオンの同時分析と生理活性物質との相関               
    13 Dec. 2019
  • 骨芽細胞様細胞MC3T3-E1の細胞内外の脂質メディエーターがアクチン細胞骨格変化を介して骨形成を制御する               
    06 Dec. 2019
  • Fabrication of Ultrahigh-Sensitivity Silicon Nanowire Biosensor by CMOS-Compatible Process for Detecting Biomolecules at Low Concentrations               
    Hui Zhang; Kei Okabe; Naoki Kikuchi; Noriyasu Ohshima; Taira Kajisa; Toshiya Sakata; Takashi Izumi; Hayato Sone
    International Conference on Mechanical, Electrical and Medical Intelligent System 2019, 04 Dec. 2019
  • シリコンナノワイヤ細線化によるバイオセンサ検出感度の評価               
    18 Sep. 2019
  • LipidBankデータベースの歴史と現状               
    Jun. 2019
  • 家庭環境内における重金属類曝露シナリオの解明-調査方法の検討               
    Jun. 2019
  • 電子線描画法による高感度シリコンナノワイヤバイオセンサの作製 およびアトモル濃度の抗原抗体特異結合の検出               
    09 Mar. 2019
  • 家庭環境内における重金属類暴露シナリオの解明ー調査方法の確立               
    Feb. 2019
  • Fabrication of Highly Sensitive Silicon Nanowire Biosensor by Electron Beam Lithography for Detecting Antigen-Antibody Specific Binding at Attomolar Concentration               
    Hui Zhang; Noriyasu Ohshima; Kakeru Oshima; Naoki Kikuchi; Taira Kajisa; Toshiya Sakata; Takashi Izumi; Hayato Sone
    GUMI 2018 (5th International Symposium of Gunma University Medical Innovation), 06 Dec. 2018
  • Novel S1P chaperone activity in the plasma from ApoM/albumin-double knockout mice               
    Nov. 2018
  • 酸化脂質膜受容体であるヒトG2Aは脳腫瘍細胞の上皮間葉転換様プロセスを制御する               
    27 May 2018
  • 一般家庭における重金属曝露メカニズムの解明-調査プロトコルについて               
    Mar. 2018
  • ゲノム編集技術を用いた蛍光蛋白ラベル法による内在性p53蛋白動態の1細胞解析               
    21 Dec. 2017
  • 骨芽細胞様細胞MC3T3-E1における分化段階に応じた機械的刺激による骨形成制御応答の解析               
    07 Dec. 2017
  • 膜貫通型リゾホスホリパーゼD、GDE4過剰発現細胞における脂質の網羅的解析               
    07 Dec. 2017
  • ゲノム編集技術を用いた蛍光蛋白ラベル法による内在性p53蛋白動態の1細胞解析               
    07 Dec. 2017
  • 脂質データベースLipidBank のWiki版構築とその特徴               
    Dec. 2017
  • スフィンゴシン1リン酸の新規担体分子の探索               
    Dec. 2017
  • 骨芽細胞様細胞MC3T3-E1における分化段階に応じた機械的刺激による骨形成制御応答               
    Dec. 2017
  • Fabrication of Silicon Nanowire Biosensor Using Electron Beam Lithography and Low-Concentration Antibody Detection               
    Yuya Sakurai; Tomoya Tashiro; Noriyasu Oshima; Kakeru Oshima; Sumio Hosaka; Takashi Izumi; Hayato Sone
    4th International Symposium of Gunma University Medical Innovation (GUMI2017), Nov. 2017
  • 電子線リソグラフィを用いたSiナノワイヤバイオセンサの作製と低濃度抗体検出               
    Oct. 2017
  • An oxidazed lipids-membrane receptor, human G2A regulates epithelial-mesenchymal transition-like proces of glioma cells.               
    30 Sep. 2017
  • 質量分析によるメタボローム解析の現状と課題               
    Jul. 2017, [Invited]
  • 化学物質曝露評価における定量的メタボロミクスの現状と課題               
    May 2017
  • 電子線リソグラフを用いた超高感度Siナノワイヤバイオセンサの創製               
    Mar. 2017
  • TRF2はコアヒストンとの直接結合によりテロメアのループ構造を維持する               
    11 Jan. 2017
  • テロメア機能不全時に染色体末端に誘導されるDNA損傷応答の細胞周期依存的な制御               
    01 Dec. 2016
  • Fabrication of N-type Silicon Nanowire Using Electron Beam Lithography for Antibody Detection               
    Yuya Sakurai; Tomoya Tashiro; Noriyasu Oshima; Kakeru Oshima; Sumio Hosaka; Takashi Izumi; Hayato Sone
    3rd International Symposium of Gunma University Medical Innovation and 8th International Conference on Advanced Micro‐Device Engineering (GUMI&AMDE 2016), Dec. 2016
  • 可溶性2-アラキドノイルグリセロール産生酵素、DDHD2の酵素学的解析               
    Jun. 2016
  • Fabrication of N-type Silicon Nanowire Using Electron Beam Lithography for Antibody Detection               
    Mar. 2016
  • Cell cycle-dependent regulation of non-homologous end joining at unprotected telomeres               
    第33回染色体ワークショップ, Jan. 2016
  • Complete sequence of human telomere DNA by single-molecule real-time sequencing technique               
    08 Dec. 2015
  • Cell cycle-dependent regulation of non-homologous end joining at unprotected telomeres               
    02 Dec. 2015
  • Glycosphingolipids Database in LipidBank Wiki Version               
    Dec. 2015
  • Fabrication of N-type Silicon Nanowire Using Electron Beam Lithography for Antibody Detection               
    Yuya Sakurai; Tomoya Tashiro; Noriyasu Oshima; Kakeru Oshima; Sumio Hosaka; Takashi Izumi; Hayato Sone
    2nd International Symposium of Gunma University Medical Innovation (GUMI2015), Dec. 2015
  • Purification and characterization of a soluble diacylglycerol lipase from rat brain               
    Araki M.; Aso C.; Ohshima N.; Tatei K.; Hirano T.; Sugimoto S.; Kishi M.; Kishimoto K.; Obinata H.; Izumi T.
    14th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases, Jul. 2015
  • Gタンパク質共役型受容体であるG2Aはがん細胞の幹細胞性を制御する               
    29 May 2015
  • 新規リゾホスファチジン酸産生酵素、GDE4・GDE7の酵素学的解析               
    May 2015
  • GDE4 and GDE7 Produce Lysophosphatidic Acid by Lysophospholipase D Activity               
    Mari Araki; Chizu Aso; Noriyasu Ohshima; Kazuaki Tatei; Tohko Hirano; Hiroyuki Sugimoto; Mikiko Kishi; Koji Kishimoto; Takashi Izumi
    The 6th international conference on Phospholipase A2 and Lipid Mediators (PLM 2015), 09 Feb. 2015, [Invited]
  • Identification and functional analyses of a novel diacylglycerol lipase from rat brain               
    Chiaki Isaji; Takahiro Kudo; Noriyasu Ohshima; Yosuke Yamashita; Mari Araki; Ayako Honda; Tomomi Nagano; Norihisa Kato; Akiyoshi Konishi; Koji Kishimoto; Kazuaki Tatei; Noriyuki Yanaka; Takashi Izumi
    The 6th international conference on Phospholipase A2 and Lipid Mediators (PLM 2015), 09 Feb. 2015, [Invited]
  • 新規酵素GDE4およびGDE7は,LPAおよびalkyl-LPAの産生に関与する               
    Jan. 2015
  • Cell Cycle-Dependent Regulation of DNA Damage Response and DNA Repair at Dysfunctional Telomeres.               
    The 4D Nucleome 2014, 18 Dec. 2014
  • Fabrication of N-type Silicon Nanowire Using FIB for Biomolecule Detection               
    Hayato Sone; Yuya Sakurai; Takashi Izumi; Sumio Hosaka
    1st International Symposium of Gunma University Medical Innovation and 6th International Conference on Advanced Micro-Device Engineering (GUMI&AMDE2014), 05 Dec. 2014
  • テロメアにおける細胞周期依存的なDNA損傷反応・DNA修復の制御機構               
    Dec. 2014
  • テロメアでの細胞周期依存的なDNA損傷反応・DNA修復反応の制御機構               
    27 Nov. 2014
  • 酸化脂質をリガンドとするGPCR, G2Aは幹細胞性制御に関わる               
    Nov. 2014
  • ラット脳ジアシルグリセロールリパーゼの精製と機能解析               
    07 Aug. 2014
  • 群馬大学におけるAdvanced OSCE の試み;医療コミュニケーション能力の評価を目的とした新規課題の導入               
    Jul. 2014
  • Gタンパク質共役型受容体、G2Aが制御するがん幹細胞性と上皮間葉転換               
    Jul. 2014, [Invited]
  • LipidBankにおける糖脂質分類:植物編               
    Jun. 2014
  • Identification and functional analyses of a novel diacylglycerol lipase from rat brain               
    2014
  • Regulation of DNA damage checkpoint termination               
    The 36th Annual Meeting of the Molecular Biology Society of Japan, 03 Dec. 2013
  • Wee1によるDNA損傷チェックポイントの回復制御               
    25 Nov. 2013
  • 9-HODE-activated GPCR, G2A Regulates Stemness of Cancer Stem Cells in Human Astrocytoma Cell Lines               
    Kishimoto K; Haraguchi T; Shimizu K; Yamaguchi A; Yoshihara T; Ohshima N; Tatei T; Tobita S; ida Y; Tsushima Y; Izumi T
    The Scripps Research Institute (San Diego), Nov. 2013, [Invited]
  • 9-HODE-activated GPCR, G2A induces epithelial-to-mesenchymal transition of human astrocytoma cells prior to generation of stem cell-like properties.               
    Kishimoto K.; Haraguchi T.; Shimizu K.; Yamaguchi A.; Yoshihara T.; Ohshima N.; Tatei K.; Tobita S.; Tsushima Y.; Izumi T.
    Society of Neuroscience 2013, Nov. 2013
  • 9-HODE-activated G2A induces epithelial-to-mesenchymal transition of human astrocytoma cells prior to generation of stem cell-like properties.               
    Kishimoto K.; Haraguchi T.; Shimizu K.; Yamaguchi A.; Yoshihara T.; Ohshima N.; Tatei K.; Tobita S.; Tsushima Y.; Izumi T.
    Society of Neuroscience 2013, Nov. 2013
  • Differentiation of malignant tumors from granulomas with dynamic [18F]-Fluoro-L-a-methyltyrosine PET imaging               
    Yamaguchi A; Iida Y; Fujisawa Y; Inamoto S; Zhao S; Suzue K; Tominaga H; Kishimoto K; Higuchi T; Hisaeda H; Izumi T; Kuge Y; Tsushima Y
    European Association of Nuclear Medicine (Lyon), Oct. 2013
  • Identification of a novel diacylglycerol lipase from rat brain               
    Sep. 2013
  • 血管平滑筋細胞に対するニコチンの分化・脱分化作用に関する解析               
    Sep. 2013
  • Gタンパク質共役型受容体、G2Aはアストロサイトーマ細胞株のがん幹細胞性を制御する               
    Sep. 2013
  • 皮膚科学におけるG2Aの役割               
    22 Jul. 2013
  • 基礎学力の向上を目指す教養教育科目「学びのリテラシー」の実践               
    Jul. 2013
  • LipidBankにおけるArchaea脂質のデータベース               
    Jul. 2013
  • Gタンパク質共役型受容体,G2Aはヒトアストロサイトーマ細胞株のがん幹細胞性を制御する               
    Jun. 2013, [Invited]
  • Subcellular distribution and binding specificity of phospholipid-binding proteins               
    Xi Xin; Kazuaki Tatei; Hideaki Ehara; Yumiko Kihara; Takashi Izumi
    JCBL (The Japanese Conference on the Biochemistry of Lipids) 55, Jun. 2013
  • 新規脳ジアシルグリセロールリパーゼの同定               
    Jun. 2013
  • 発光測定に基づく低酸素細胞・組織イメージング技術の開発と医学応用               
    Apr. 2013
  • アストロサイトーマU251細胞の幹細胞性と上皮間葉転換制御に関わるGタンパク質共役型受容体G2Aの役割               
    Dec. 2012
  • 抗ロイコトリエンC4モノクローナル抗体とその単鎖抗体によるロイコトリエン中和作用               
    Dec. 2012
  • ロイコトリエンに対する単鎖抗体を利用した抗体治療薬開発に向けた基礎研究               
    Nov. 2012
  • Oxidized Free Fatty Acids-Activated GPCR, G2A Regulates Stemness and Malignant Behavior of An Astrocytoma Cell Line               
    Neuroscience 2012, Oct. 2012
  • G2A Regulates Stemness and malignant behavior of Astrocytoma Cells.               
    Sep. 2012
  • アンケート調査からみた生涯教育への臨床医のニーズ ー群馬大学医学教育センターリカレント教育部門の活動ー               
    Jul. 2012
  • がん幹細胞性制御におけるG2Aの役割               
    Jun. 2012, [Invited]
  • 酸化遊離脂肪酸をリガンドとするGタンパク質共役型受容体、G2Aはアストロサイトーマ細胞株のがん幹細胞性を制御し、悪性度を規定する               
    Jun. 2012
  • ロイコトリエン作用に対する抗ロイコトリエンC4単鎖抗体の中和効果               
    May 2012
  • Gタンパク質共役型受容体、G2Aを介したがん幹細胞性制御               
    May 2012
  • A stimulus-dependent, dentate gyrus-specific novel phospholipase A2               
    Nov. 2011
  • グリオーマ細胞におけるG2Aを介した形質変化の制御               
    Nov. 2011, [Invited]
  • G2Aは神経膠腫細胞株U251に栄養飢餓及び低酸素刺激に対する抵抗性を賦与する               
    Sep. 2011
  • Expression of a single-chain antibody that neutralizes the effect of cysteinyl leukotrienes               
    Takahashi Y; Kawakami Y; Hirano S; Kinoshita M; Otsuki A; Yamamoto TS; Kurahashi Y; Daiyasu H; Toh H; Kishimoto K; Izumi T; Yamamoto S
    52nd International Conference on the Bioscience of Lipids, 30 Aug. 2011, [Invited]
  • 哺乳動物のGDE群とマウスGDE5の非酵素的機構による骨格筋分化制御               
    Aug. 2011
  • 生理活性脂質研究の新展開               
    Jun. 2011
  • 酪酸ナトリウムでラット肝臓幹様細胞のAnnexin A3 の発現が抑制される               
    Dec. 2010
  • マウス由来グリセロホスホジエステルホスホジエステラーゼ1(GDE1)の基質特異性と組織分布の解析               
    Dec. 2010
  • pColdベクターを用いた5-リポキシゲナーゼ(5-LO)の大量発現と精製               
    Dec. 2010
  • Cytosolic phospholipase A2 alpha amplifies early cyclooxygenase-2 expression, oxidative stress and MAP kinase phosphorylation after cerebral ischemia in mice               
    Dec. 2010
  • pColdベクターを用いた5-リポキシゲナーゼ (5-LO)の大量発現と精製               
    Nov. 2010
  • 酸化遊離脂肪酸をリガンドとするG2Aの機能とサブタイプの解析               
    May 2010
  • アシルプロテインチオエステラーゼ1/リゾホスホリパーゼ1の活性と細胞内局在               
    May 2010
  • Novel function of 9(S)-hydroxyoctadecadienoic acid on proliferation of T cells               
    May 2010
  • Ceramide induces myogenic differentiation and apoptosis in Drosophila Schneider cells.               
    Dec. 2009
  • Functional role of a novel glycerophosphodiester phosphodiesterase GDE5 during myoblast differentiation.               
    Dec. 2009
  • ほ乳類グリセロホスホジエステルホスホジエステラーゼの酵素学的解析               
    Nov. 2009
  • 9-HODE induces cell growth arrest in Jurkat T lymphocytes.               
    Oct. 2009
  • Proteomic analysis of rat hepatic stem-like cells respond to sodium butyrate reversibly.               
    Sep. 2009
  • Detection of Receptor protein tyrosine kinase-mediated cytoskeletal rearrangement in living cells using surface plasmon resonance.               
    Sep. 2009
  • High methionine diet-induced acute hepatitis in CSE-deficient mice.               
    Sep. 2009
  • 表面プラズモン共鳴現象を用いた生細胞におけるGPCRシグナルの検出               
    Jul. 2009
  • The transcriptional regulation of Ets2 and CTP:phosphocholine cytidylyltransferase alfa in M-CSF stimulated RAW264 osteoclast precursor cells.               
    Okamura K.; Takagishi K.; Yamashita S.; Aoyama C.; Horibata Y.; Izumi T.; Vance D.; Sugimoto H.
    55th Annual Meeting of the Orthopaedic Research Societies, May 2009
  • Characterization of mouse glycerophosphodiester phosphodiesterase 1 (GDE1)               
    Noriyasu Ohshima; Mayumi Kaneko; Naoko Takahashi; Koji Takio; Yoshitsugu Shiro; Kazuaki, Tatei; Takashi Izumi
    4th International Conference on Phospholipase A2 and Lipid Mediators, May 2009
  • Ceramide induces myogenic differentiation and apoptosis in Drosophila Schneider cells               
    Kazuaki Tatei; Hidemasa Kawamura; Tetsuo Nonaka; Hideru Obinata; Tomoyasu Hattori; Ai Ogawa; Hideko Kazama; Nobuyuki Hamada; Tomoo Funayama; Tetsuya Sakashita; Yasuhiko Kobayashi; Takashi Nakano; Takashi Izumi
    4th International Conference on Phospholipase A2 and Lipid Mediators, May 2009
  • Oxidized free fatty acids mediate alarm signals through a G-protein coupled receptor, G2A               
    Takashi Izumi; Hideru Obinata; Ai Ogawa; Tomoyasu Hattori; Mikiko Kishi; Noriyasu Ohshima; Kexin Chen; Melisa Intan Barliana; Kazuaki Tatei
    4th International Conference on Phospholipase A2 and Lipid Mediators, May 2009
  • 新規因子GDE5の筋芽細胞分化における役割、および骨格筋特異的GDE5過剰発現マウスの形質の解析               
    Mar. 2009
  • Characterization of a neutral sphingomyelinase homolog as a phosphodiesterase for phosphoethanolamine ceramide in Drosophila cells               
    Kazuaki TATEI; Hidemasa KAWAMURA; Tetsuo NONAKA; Hideru OBINATA; Tomoyasu HATTORI; Ai OGAWA; Hideko KAZAMA; Nobuyuki HAMADA; Tomoo FUNAYAMA; Tetsuya SAKASHITA; Yasuhiko KOBAYASHI; Takashi NAKANO; Takashi IZUMI
    4th COE International Symposium, Nov. 2008
  • STUDY OF BUTYRATE SIGNAL TRANSDUCTION PATHWAYS IN RATHEPATIC STEM-LIKE CELLS               
    Nov. 2008
  • Gタンパク質共役型受容体G2Aのリガンド同定と機能解析               
    Jul. 2008
  • マウス由来グリセロホスホジエステルホスホジエステラーゼ1(GDE1)の酵素学的解析               
    Jun. 2008
  • リゾホスホリパーゼ1の脱パルミトイル化活性の解析               
    Jun. 2008
  • 酸化遊離脂肪酸をリガンドとするG2Aの生理機能               
    Jun. 2008
  • Gタンパク質共役型受容体G2Aの新規スプライシングバリアントの同定と機能解析               
    Jun. 2008
  • 9-hydroxyoctadecadienoic acid, one of the oxidized metabolites of linoleic acid, induces cell cycle arrest in the G1 phase in primary human keratinocytes               
    Hideru Obinata; Takashi Izumi
    International Workshop on Cell Regulation in Division and Arrest Under Stress, Apr. 2008
  • 脱パルミトイル化酵素としてのリゾホスホリパーゼ1の解析               
    Dec. 2007
  • Ets2の核内(NLS)および核外移行シグナル(NES)の同定およびRAW293細胞を用いたM-CSF刺激によるCTP:phosphocholine cytidylyltransferaseα(CTα)転写促進におけるEts2の重要性               
    Dec. 2007
  • 生細胞におけるGPCR活性の表面プラズモン共鳴(SPR)による観察               
    Dec. 2007
  • ラット肝臓幹様(HSL)細胞を酪酸処理したときのProhibitin の応答               
    Dec. 2007
  • Gタンパク質共役型受容体G2Aのスプライシングバリアントの同定と機能解析               
    Dec. 2007
  • 表皮角化細胞におけるGタンパク質共役型受容体G2Aの生理作用               
    Jun. 2007
  • G2A MEDIATES SIGNALS OF OXIDIZED FREE FATTY ACIDS IN HUMAN KERATINOCYTES               
    Hideru Obinata; Tomoyasu Hattori; Ai Ogawa; Kazuaki Tatei; Takashi Izumi
    3rd International Conference on Phospholipases A2 and Lipid Mediators, May 2007
  • OXIDIZED FREE FATTY ACID-G2A SIGNALING MEDIATES ALARM SIGNAL UNDER OXIDATIVE STRESS               
    Takashi Izumi; Hideru Obinata; Tomoyasu Hattori; Ai Ogawa; Kexin Chen; Melisa Intan Barliana; Mikiko Kishi; Kazuaki Tatei
    3rd International Conference on Phospholipases A2 and Lipid Mediators, May 2007
  • ロイコトリエン研究の最近の進歩               
    Mar. 2007
  • Gタンパク質共役型受容体G2Aのリガンド同定と皮膚における生理機能の解析               
    Oct. 2006
  • Gタンパク質共役型受容体G2Aのリガンド同定とシグナル解析               
    Jun. 2006
  • Bioluminescence Resonance Energy Transfer によるロイコトリエンB4受容体二量体の検出               
    Jun. 2006
  • ショウジョウバエ初期胚における放射線誘導性アポトーシスの解析               
    Jun. 2006
  • Proteome analysis of hepatocyte stem-like (HSL) cell differentiation.               
    Toshihiko Saheki; Hitomi Ito; Naoyuki Takayama; Kentaro Nakamura; Akihiro Sekiguchi; Atsuyoshi Nishina; Takashi Izumi; Toshihiro Sugiyama; Masaharu Seno; Itaru Kojima
    20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress, Jun. 2006
  • Cystathionine gamma-lyase-deficient mice as animal models for cystathioninaemia               
    Noriyuki Akahoshi; Takashi Izumi; Yasuki Ishizaki; Isao Ishii
    20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress, Jun. 2006
  • Partial purification of natural ligands for orphan G-protein coupled receptors               
    Takashi Tujii; Hideru Obinata; Takashi Izumi; Shigeki Takeda
    20th IUBMB international congress of biochemistry and molecular biology and 11th FAOBMB congress, Jun. 2006
  • Purification and characterization of lysophospholipase D from rat brain               
    Sayaka Sugimoto; Hiroyuki Sugimoto; Chizu Aso; Takashi Izumi
    20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress, Jun. 2006
  • Human G2A is a G protein-coupled receptor activated by 9-hydroxyoctadecadienoic acid and other oxidized free fatty acids               
    Hideru Obinata; Tomoyasu Hattori; Kazuaki Tatei; Takashi Izumi
    20th IUBMB international congress of biochemistry and molecular biology and 11th FAOBMB congress, Jun. 2006
  • Detection of GPCR activity by surface plasmon resonance (SPR) in living cells               
    Chen Kexin; Hideru Obinata; Kohei Hosaka; Takashi Izumi
    20th IUBMB international congress of biochemistry and molecular biology and 11th FAOBMB congress, Jun. 2006
  • Identification of nuclear-export-signal(NES) and nuclear-localization-signal(NLS) of Ets-2,and their relationship to the transcriptional regulation of CTP:phosphocholine Cytidylyltransferase α               
    Koichi Okamura; Takashi Izumi; Kenji Takagishi; Dennis E. Vance; Hiroyuki Sugimoto
    20th IUBMB international congress of biochemistry and molecular biology and 11th FAOBMB congress, Jun. 2006
  • Lysophospholipase is a deacylating enzyme useful for the detection of palmitoylated peptide by MALDI-TOF mass spectrometry               
    Tohko HIRANO; Merisa I BARLIANA; KISHI MIKIKO; Hiroyuki SUGIMOTO; Chie MURATA; Ryo TAGUCHI; IZUMI TAKASHI
    20th IUBMB International Congress of Biochemistry and Molecular Bioligy and 11th FAOBMB Congress, Jun. 2006
  • The roles of G2A in human keratinocytes as a receptor for 9-hydroxyoctadecadienoic acid               
    Tomoyasu Hattori; Hideru Obinata; Ai Ogawa; Kazuaki Tatei; Osamu Ishikawa; Takashi Izumi
    20th IUBMB international congress of biochemistry and molecular biology and 11th FAOBMB congress, Jun. 2006
  • 酸化遊離脂肪酸の受容体G2Aのヒト表皮角化細胞における生理的役割               
    May 2006
  • Detection of GPCR activity by surface plasmon resonance (SPR) in living cells               
    Chen K.; Obinata H.; Izumi T.
    Keystone Symposia, G Protein-Coupled Receptors: Evolving Concepts and New Tchniques, Feb. 2006
  • Analysis of the dimerization/ oligomerization of Leukotriene B4 receptors by BRET               
    Kishi M; Obinata H; Barliana M I; Izumi T
    Keystone Symposia, G Protein-Coupled Receptors: Evolving Concepts and New Tchniques, Feb. 2006
  • ショウジョウバエの初期胚に対する重粒子線照射の影響               
    Jan. 2006
  • A biological role of G2A in human keratinocytes as a receptor for oxidized free fatty acids               
    Hattori, T.; Obinata, H.; Ogawa, A.; Izumi, T.
    Keystone Symposia, Eicosanoid in Inflammation and Chronic Disease, Jan. 2006
  • Identification of 9-hydroxyoctadecadienoic acid and other oxidized free fatty acids as ligands of the G-protein coupled receptor G2A               
    Obinata, H.; Hattori, T.; Tatei, K.; Izumi, T.
    Keystone Symposia, Eicosanoid in Inflammation and Chronic Diseases, Jan. 2006
  • ヒトGタンパク質共役受容体MrgX2のリガンド探索               
    Dec. 2005
  • ヒト表皮角化細胞においてリノール酸酸化物が及ぼす影響               
    Dec. 2005
  • Analysis of the mechanism of dimerization/ oligomerization of leukotriene B4 Receptors               
    Dec. 2005
  • ショウジョウバエ・ホスホリパーゼD遺伝子の強制発現による解析               
    Dec. 2005
  • An UV-inducible G protein-coupled receptor, G2A, functions as a receptor for oxidized free fatty acid such as 9-hydroxyoctadecadienoic acid.               
    H. Obinata; T. Hattori; A. Ogawa; K. Tatei; T. Izumi
    21st century COE Program, The second international symposium on biomedical research using accelerator technology., Nov. 2005
  • ケラチノサイトにおけるリノール酸酸化物の影響               
    Nov. 2005
  • Effects of heavy-ion irradiation on the early embryo of Drosophila melanogaster               
    TATEI KAZUAKI; OBINATA HIDERU; NONAKA TETUO; NAKANO TAKASHI; IZUMI TAKASHI
    21st century COE Program, The second international symposium on biomedical research using accelerator technology., Nov. 2005
  • Femtogram Mass Biosensor Using a Self-sensing Cantilever for Allergy Check               
    Hayato Sone; Ayumi Ikeuchi; Takashi Izumi; Haruki Okano; Sumio Hosaka
    The 13th International Conference on Scanning Tunneling Microscopy/Spectroscopy and Related Techniques, Jul. 2005
  • 表面プラズモン共鳴法(SPR)を用いたGタンパク質共役型受容体のシグナル解析               
    16 Jun. 2005
  • Bioluminescence Resonance Energy Transfer(BRET)を用いたロイコトリエンB4受容体二量体化の解析               
    16 Jun. 2005
  • 多機能酵素としての低分子型リゾホスホリパーゼとその質量分析への応用               
    Jun. 2005
  • Detection of the dimerization of the leukotriene B4 receotor using BRET               
    Jun. 2005
  • カンチレバー型フェムトグラムバイオセンサを用いた抗体抗原反応測定               
    Apr. 2005
  • Femtogram mass biosensor using a self-sensing cantilever for an allergy checker               
    Sumio Hosaka; Takafumi Chiyoma; Ayumi Ikeuchi; Haruki Okano; Hayato Sone; Takashi Izumi
    2nd International Conference on Advanced Materials and Nanotechnology, Feb. 2005
  • Femtogram mass biosensor using a piezoresistive cantilever in water               
    Hayato Sone; Ayumi Ikeuchi; Takashi Izumi; Haruki Okano; Sumio Hosaka
    The 12th International Colloquium on Scanning Probe Microscopy, Dec. 2004
  • Bioluminescence Resonance Energy Transfer(BRET)によるロイコトリエンB4受容体二量体化の検出               
    Dec. 2004
  • ショウジョウバエ・ホスホリパーゼD遺伝子の同定と強制発現による解析               
    Dec. 2004
  • Actin assembly is a crucial factor for PAF-induced superoxide anion generation from adherent human eosinophils               
    Suzuki, M.; Kato, M.; Hanaka, H.; Izumi, T.; Morikawa, A.
    2nd International Conference on Phospholopase A2 and 8th International Congress on Platelet-Activating Factor and Lipid Mediators, Oct. 2004
  • Transcriptional regulation for CTP:phosphocholine cytidylyltransferase alfa               
    Sugimoto, H.; Okamura, K.; Sugimoto, S.; Vance, D. E.; Izumi, T.
    2nd International conference on phospholipase A2 and 8th international congress on Platelet-activating factor and related lipid mediators, Oct. 2004
  • Functional analysis of Phospholipase D gene in Drosophila               
    Izumi, T.; Tatei, K.
    2nd International conference on phospholipase A2 and 8th international congress on Platelet-activating factor and related lipid mediators, Oct. 2004
  • Overexpression of the Phospholipase D gene affects the external sensory organ cell fate in Drosophila               
    Tatei, K.; Izumi, T.
    2nd International Conference on Phospholopase A2 and 8th International Congress on Platelet-Activating Factor and Lipid Mediators, Oct. 2004
  • カンチレバー共振型ピコグラムセンサー               
    Sep. 2004
  • Femtogram mass sensor using a piezo resistive cantilever for bioscience               
    Hayato Sone; Yoshinori Fujinuma; Takashi Hieida; Takafumi Chiyoma; Haruki Okano; Sumio Hosaka
    Intern. Conf. Micro and Nano Engineering 2004, Aug. 2004
  • Detection of the Leukotriene B4 Receptor Dimerizarion/ Oligomerization in living cells by Bioluminescence Resonance Energy Transfer (BRET).               
    27 May 2004
  • 5-リポシキゲナーゼの細胞内局在と活性制御               
    Mar. 2004
  • Regulation of the transcription for CTP:phosphocholione cytidylyltransferase a: roles of Sp1 as a co-activator with Ets-1, and Net as an important repressor               
    Dec. 2003
  • Characterization of kainite-inducible dentate gyrus-specific cytosolic phospholipase A2 (KIDSCPLA2)               
    Kishimoto, K.; Nakadate, K.; Shirasawa, T.; Izumi, T.; Uozumi, N.; Watanabe, Y.; Shimizu, T.
    33rd Society for Neuroscience annual meeting, Nov. 2003
  • Overexpression of the Phospholipase D gene in Drosophila.               
    Tatei, K.; Izumi, T.
    First COE International Symposium, Gunma University, "Molecular Mechanisms of Vesicle Trafficking and Membrane Fusion", Nov. 2003
  • Identification of Ets-1 as an Important Transcriptional Activator of CTP:Phosphocholine Cytidylyltransferase a in COS-7 Cells and Co-Activation with Transcriptional Enhancer Factor-4               
    Oct. 2003
  • The mechanism of intracellular localization of LTA4H               
    Oct. 2003
  • LTA4水解酵素の細胞内局在とそのメカニズムについて               
    Jun. 2003
  • 5-oxo-ETE受容体の活性化が引き起こすケモタキシスと細胞内セカンドメッセンジャー濃度変化の測定               
    Jun. 2003
  • Glucocorticoids Up-regulate Leukotriene B4 Receptor-1 Expression in HL-60 Cells and Human Neutrophils               
    Obinata, H.; Yokomizo, T.; Shimizu, T.; Izumi, T.
    Keystone Symposia, Eicosanoid Lipid Mediators: From Molecular Discovery to Clinical Application, Mar. 2003
  • Molecular Cloning and Regulation of Two Leukotriene B4 Receptor               
    Izumi, T.; Obinata, H.; Yokomizo, T.; Shimizu, T.
    Keystone Symposia, Eicosanoid Lipid Mediators: From Molecular Discovery to Clinical Application, Mar. 2003
  • ショウジョウバエホスホリパーゼD(dPld)遺伝子の強制発現による機能解析               
    Nov. 2002
  • 脳におけるアラキドン酸含有LPAの2-アラキドノイルグリセロールへの酵素的変換               
    Nov. 2002
  • ロイコトリエンB4受容体-1のグルココルチコイドによる発現上昇               
    Oct. 2002
  • ショウジョウバエホスホリパーゼD遺伝子の強制発現による機能解析               
    Oct. 2002
  • 生理活性脂質LPAの分析法に関する研究               
    Sep. 2002
  • 生理活性脂質の基礎と臨床               
    Sep. 2002, [Invited]
  • 5-リポキシゲナーゼの細胞内局在と活性制御               
    30 Aug. 2002
  • キイロショウジョウバエのホスホリパーゼD遺伝子の単離と解析               
    Jun. 2002
  • ロイコトリエンB4受容体-1のグルココルチコイドによる発現および機能の亢進               
    Jun. 2002
  • Current topics on leukotriene research               
    Izumi T.
    The 12th Congress of Interasma Japan/ North Asia, 06 Mar. 2002
  • 脳の脂質とオーファン受容体               
    Mar. 2002
  • ロイコトリエンB4 と病態               
    Mar. 2002
  • Receptor-dependent Metabolism of PAF by Macrophage               
    2002
  • 脳神経系特異的な新規 G タンパク質共役型受容体の遺伝子クローニング               
    Dec. 2001
  • 5-リポキシゲナーゼの細胞内局在と移行               
    25 Oct. 2001
  • 5-リポキシゲナーゼの細胞内局在と移行               
    Oct. 2001
  • マウスマクロファージにおける受容体依存的なPAFの分解               
    Oct. 2001
  • Characterization of lysophospholipase D activity in rat brain               
    Sugimoto, H.; Iijima, T.; Nakane, S.; Izumi, T.
    Seventh International Congress on Platelet-Activating Factor and Lipid Mediators, Sep. 2001
  • Characterization of two cysteinyl leukotriene receptors (CysLT1 and CysLT2) from mouse               
    Ogasawara, H.; Ishii, S.; Yokomizo, T.; Shimizu, T.; Izumi, T.
    Seventh International Congress on Platelet-Activating Factor and Lipid Mediators, Sep. 2001
  • Glucocorticoid up-regulates leukotriene B4 receptor expression in HL-60 cells differntiation into neutrophils               
    Obinata, H.; Yokomizo, T.; Shimizu, T.; Izumi, T.
    Seventh International Congress on Platelet-Activating Factor and Lipid Mediators, Sep. 2001
  • Translocation and localization of 5-lipoxygenase               
    Hanaka, H.; Shimizu, T.; Izumi, T.
    Seventh International Congress on Platelet-Activating Factor and Lipid Mediators, Sep. 2001
  • Receptor-Dependent Metabolism of PAF by Macrophage               
    Sep. 2001
  • 5-リポキシゲナーゼの細胞内局在と移行               
    03 Jul. 2001
  • TRANSLOCATION AND LOCALIZATION OF 5-LIPOXYGENASE               
    Apr. 2001
  • 生理活性脂質と気管支喘息               
    2001, [Invited]
  • ロイコトリエン B4 受容体発現に及ぼすグルココルチコイドの影響               
    Dec. 2000
  • ロイコトリエン B4 第二受容体 BLT2 のクローニングと解析               
    Dec. 2000
  • EGFP との融合タンパク質を用いた 5 -リポキシゲナーゼの細胞内局在と膜移行の解析               
    Dec. 2000
  • Translocaion and localization of 5-lipoxygenase.               
    H. Hanaka; T. Shimizu; T. Izumi
    The 3rd International Conference on Oxygenases, 26 Nov. 2000
  • Characterization of two forms of leukotriene B4 receptors.               
    T. Shimizu; T. Yokomizo; T. Izumi
    The 3rd International Conference on Oxygenases, 26 Nov. 2000
  • 第二のロイコトリエンB4受容体BLT2のクローニングと解析               
    Oct. 2000
  • ロイコトリエン受容体               
    Oct. 2000
  • ロイコトリエンの産生制御と受容体               
    Oct. 2000
  • NLS- and NES-dependent mechanisms determine the localization of 5-lipoxygenase               
    Hanaka, H.; Shimizu, T.; Izumi, T.
    11th International Conference on Advances in Prostaglandin and Leukotriene Research, Jun. 2000
  • Structures and Functions of Leukotriene B4 Receptors               
    T. Yokomizo; E. Noiri; K. Kato; K. Masuda; A. Toda; N. Ito; T. Izumi; T. Shimizu
    11th International Conference on Advances in Prostaglandin and Leukotriene Research, Jun. 2000
  • Leukotriene B4 Receptors: from clones to clinics               
    T. Shimizu; T. Izumi; T. Yokomizo
    11th International Conference on Advances in Prostaglandin and Leukotriene Research, Jun. 2000
  • Cloning and characterization of rat leukotriene B4 receptor               
    Toda, A.; Yokomizo, T.; Masuda, K.; Nakao, A.; Izumi, T.; Shimizu, T.
    11th International Conference on Advances in Prostaglandin and Leukotriene Research, Jun. 2000
  • Cloning and expression of the mouse leukotriene D4 receptor               
    Ogasawara, H.; Izumi, T.; Shimizu, T.
    11th International Conference on Advances in Prostaglandin and Leukotriene Research, Jun. 2000
  • Transcriptional mechanism of human leukotriene B4 receptor               
    Kato, K.; Yokomizo, T.; Izumi, T.; Shimizu, T.
    11th International Conference on Advances in Prostaglandin and Leukotriene Research, Jun. 2000
  • Critical roles of PAF receptor and cPLA2 in acute lung injury               
    Ishii, S.; Uozumi, N.; Kume; K; Izumi, T.; Shimizu, T.; Nagase, T.; Ouchi, Y.
    11th International Conference on Advances in Prostaglandin and Leukotriene Research, Jun. 2000
  • Intracellular localization of LTA4 Hydrolase               
    Ide, Y.; Izumi, T.; Shimizu, T.
    11th International Conference on Advances in Prostaglandin and Leukotriene Research, Jun. 2000
  • Leukotriene D4 activates microglia through the CysLT1 receptor               
    Hirabayashi, T.; Ogasawara, H.; Izumi, T.; Shimizu, T.
    11th International Conference on Advances in Prostaglandin and Leukotriene Research, Jun. 2000
  • Localization and translocation of enzymes involved in leukotriene biosynthesis               
    Izumi T.; Hanaka H.; Ide Y.; Hirabayashi T.; Shimizu T.
    11th International Conference on Advances in Prostaglandin and Leukotriene Research, Jun. 2000
  • マウスのロイコトリエンD4受容体のクローニングと発現               
    Jun. 2000
  • 脂質メディエーターと生体制御-ロイコトリエン受容体を中心に               
    Jun. 2000
  • ヒトロイコトリエンB4受容体遺伝子の転写機構の解析               
    Dec. 1999
  • ロイコトリエンの産生制御と受容体               
    Nov. 1999
  • アラキドン酸カスケード               
    Oct. 1999
  • Localization and translocation of enzymes involved in the synthesis of leukotrienes.               
    Izumi, T.; Hanaka, H.; Ide, Y.; Hirabayashi, T.; Shimizu, T.
    6th International Conference on Eicosanoids & Other Bioactive Lipids in Cancer, Inflammation and Related Diseases, Sep. 1999
  • Leukotriene B4 receptor: Structure, transcriptional regulation, and intracellular signaling.               
    Yokomizo, T.; Kato, K.; Masuda, K.; Toda, A.; Ito, N.; Izumi, T.; Shimizu, T.
    6th International Conference on Eicosanoids & Other Bioactive Lipids in Cancer, Inflammation and Related Diseases, Sep. 1999
  • Rapid activation of HepG2 cells by 17beta-estradiol               
    Obinata, H.; Izumi, T.; Shimizu, T.
    FASEB Summer Reseach Conference, 08 Aug. 1999
  • ロイコトリエンB4受容体:細胞内情報伝達、転写調節機構               
    Jul. 1999
  • モルモットロイコトリエンB4受容体cDNAのクローニング及び機能解析               
    Jun. 1999
  • EGFPとの融合タンパク質を用いた5-リポキシゲナーゼの細胞内局在と膜移行の解析               
    花香 博美; 和泉 孝志; 清水 孝雄
    Jun. 1999
  • 脂質受容体               
    Apr. 1999
  • アラキドン酸カスケードの新展開               
    Apr. 1999
  • cDNA cloning and characterization of guinea-pig leukotriene B4 receptor               
    Masuda, K.; Yokomizo, T.; Izumi, T.; Shimizu, T.
    Keystone Symposium, Mar. 1999
  • Cellular localization and teranslocation of 5-lipoxygenase               
    Hanaka, H.; Izumi, T.; Shimizu, T.
    Keystone Symposium, Mar. 1999
  • メディエーター最前線 ロイコトリエン               
    Mar. 1999
  • ロイコトリエンB4受容体の構造と細胞内情報伝達               
    Oct. 1998
  • Regulation of Expression of PAF Receptor on Eosinophils in Allergic Inflammation               
    S. Kishimoto; T. Sugiura; T. Izumi; T. Shimizu; H. Sagara; T. Fukuda; S. Makino; K. Waku
    6th International Congress on Platelet-activating Factor and Related Lipid Mediators, Oct. 1998
  • Agonist-Induced Sequestration and Recycling of PAF Receptor               
    E. Saito; I. Ishii; T. Izumi; T. Shimizu
    6th International Congress on Platelet-activating Factor and Related Lipid Mediators, Oct. 1998
  • Properties of leukotriene B4 receptor               
    Izumi T.; Yokomizo T.; Igarashi T.; Masuda K.; Kato K.; Toda A.; Shimizu T.
    6th International Congress on Platelet-activating Factor and Related Lipid Mediators, Oct. 1998
  • ロイコトリエンとアレルギー疾患               
    Apr. 1998
  • Molecular cloning of leukotriene B4 receptor               
    Yokomizo, T.; Izumi, T.; Shimizu, T.
    Keystone Symposia on Molecular and Cellular Biology, 23 Mar. 1998
  • ロイコトリエンB4受容体のクローニングと性質               
    Nov. 1997
  • cDNA cloning of LTB4 receptor.               
    Izumi, T.; Yokomizo, T.; Shimizu, T.
    5th International Conference on Eicosanoids & Other Bioactive Lipids in Cancer, Inflammation and Related Diseases, Sep. 1997
  • cDNA cloning and functional expression of a human leukotriene B4 receptor.               
    Yokomizo, T.; Izumi, T.; Chan, K.; Takuwa, Y.; Shimizu, T.
    Sep. 1997
  • Molecular cloning of leukotriene B4 receptor.               
    Yokomizo, T.; Izumi, T.; Shimizu, T.
    17th International Congress of Biochemistry and Molecular Biology, Aug. 1997
  • PAF受容体 -遺伝子から臨床まで-               
    Apr. 1997
  • Pathophysiological roles of PAF in vivo.               
    Ishii, S.; Kume, K.; Izumi, T.; Shimizu, T.; Nagase, T.; Fukuchi, Y.; Kuwaki, T.; Kumada, M.; Ikuta, K.; Tashiro, H.; Miyazaki, J.-I.; Noma, M.
    10th International Conference on Prostaglandins and Related Compounds, Oct. 1996
  • Exchanges of polar amino acids to alanines of platelet-activating factor receptor generate constitutive active and inactive mutants with altered affinities and altered cellular responses to their ligands.               
    Ishii, I.; Izumi, T.; Ui, M.; Shimizu, T.
    10th International Conference on Prostaglandins and Related Compounds, Sep. 1996
  • Platelet-activating factor receptor - Signal transduction and gene regulation.               
    Shimizu, T.; Izumi, T.
    10th International Conference on Prostaglandins and Related Compounds, Sep. 1996
  • cDNA Cloning of Leukotriene B4 12-Hydroxydehydrogenase               
    Izumi T.; Yokomizo T.; Shimizu T.
    10th International Conference on Prostaglandins and Related Compounds, Sep. 1996
  • Exchanges of polar amino acids to alanine generate platelet-activating factor receptor mutants with altered affinities to their ligand.               
    Ishii, I.; Izumi, T.; Ui, M.; Shimizu, T.
    American Society of Investigative Pathology, American Association of Immunologists, Jun. 1996
  • アレルギー性気管支喘息における好酸球PAF受容体の発現               
    Feb. 1996
  • PAFトランスジェニックマウスの解析               
    Feb. 1996
  • 血小板活性化因子受容体のリガンド結合部位の解析               
    Feb. 1996
  • PAFと気管支喘息               
    1996
  • 血小板活性化因子受容体およびロイコトリエン受容体について               
    1996, [Invited]
  • Cloning and characterization of a platelet-activating factor receptor gene.               
    Ishii, S.; Nakamura, M.; Waga, I.; Kume, K.; Izumi, T.; Shimizu, T.
    4th International Conference on Eicosanoids & Other Bioactive Lipids in Cancer, Inflammation and Radiation Injury, Oct. 1995
  • Expression and mutagenetic study of leikotriene B4 12-hydroxydehydrogenase.               
    Yokomizo, T.; Kume, K.; Izumi, T.; Shimizu, T.
    4th International Conference on Eicosanoids & Other Bioactive Lipids in Cancer, Inflammation and Radiation Injury, Oct. 1995
  • ブタ白血球ロイコトリエンB4受容体の部分精製と再構成               
    Apr. 1995
  • PAF受容体を介する細胞内応答               
    Mar. 1995
  • Regulation and signal transduction of PAF receptor.               
    Izumi, T.
    FASEB Summer Research Conferences on Cytokine and Lipid Mediator Networks, 1995, [Invited]
  • Regulation and signal transduction of PAF receptor.               
    Izumi, T.; Honda, Z.; Mutoh, H.; Kume, K.; Shimizu, T.
    9th International Conference on Prostaglandins and Related Compounds, Jun. 1994, [Invited]
  • Purification and characterization of leukotriene B4 (LTB4) 12-hydroxydehydrogenase.               
    Yokomizo, T.; Uozumi, N.; Izumi, T.; Shimizu, T.
    9th International Conference on Prostaglandins and Related Compounds, Jun. 1994
  • エイコサノイド・PAF受容体と情報伝達               
    Apr. 1994
  • LTB4とPAFについての最近の研究               
    1994
  • Biosynthesis and Metabolism of Leukotriene (LT)B4.               
    Yokomizo, T.; Minami, M.; Izumi, T.; Shimizu, T.
    International Symposium on Molecular Biology of the Arachidonate Cascade, Dec. 1993
  • Characterization of the PAF receptor.               
    Izumi, T.; Honda, Z.; Mutoh, H.; Shimizu, T.
    International Symposium on Molecular Biology of the Arachidonate Cascade, Dec. 1993
  • PAF受容体を介する情報伝達の解析               
    Dec. 1993
  • 血小板活性化因子(PAF)による生体制御 -PAF受容体のクローニングと情報伝達-               
    Nov. 1993
  • PAF受容体を介する情報伝達の解析               
    Oct. 1993
  • Leukotriene A4 hydrolase, a bifunctional enzyme               
    Izumi T.; Minami M.; Ohishi N.; Bito H.; Shimizu T.
    The 8th International Conference on Prostaglandins and Related Compounds, Jul. 1992
  • 血小板活性化因子と情報伝達               
    Jun. 1992
  • Leukotriene A4 hydrolase, a bifunctional enzyme.               
    Izumi, T.; Minami, M.; Bito, H.; Shimizu, T.
    First IUBMB Conference, Biochemistry of Dieseases, Jun. 1992
  • PAF受容体と情報伝達               
    1992, [Invited]
  • 脂質性メディエーターによる細胞制御               
    1992
  • Biosynthesis of leukotriene C4.               
    Izumi, T.; Shimizu, T.; Tsuchida, S.; Sato, K.
    First Biennial International Conference on Amino Acid Research, Aug. 1991
  • PAF受容体について               
    1991
  • アラキドン酸のリポキシゲナーゼファミリーについて               
    1991
  • ロイコトリエン(LT)A4の代謝 LTA4水解酵素とLTC4合成酵素の精製及び性質               
    Jul. 1987
    ヒト肺よりLTA4水解酵素を,モルモット肺よりLTC4合成酵素の精製を行い,その性質につき検討した.ヒト肺のLTA4水解酵素は,均一な蛋白に精製され,分子学的性質において,ヒト白血球の酵素と類似し,基質であるLTA4の他,基質とならないLTA4 isomerによっても不活性化された.モルモット肺のLTC4合成酵素は,ミクロソーム画分に回収され,塩及びdetergentにより可溶化された.本酵素活性はゲル濾過カラム等にてグルタチオン-S-トランスフェラーゼ活性と分離され,さらにイオン交換,ハイドロキシアパタイトカラムにて部分精製された
  • モルモット全身臓器におけるLTA4水解(LTB4合成)酵素活性およびLTC4合成酵素活性の分布               
    Jun. 1986
    LTA4を基質としたときのLTA4水解(LTB4合成)酵素活性およびLTC4合成酵素活性のモルモット主要臓器における分布を測定し,血球細胞に比べて種々の臓器に高いLT合成活性のあることを見出した.この知見は炎症反応における各臓器の果たす役割や,臓器の機能に関係したLTの作用を知る上で重要である
  • マウスマスト細胞のカルシウム依存性5-リポキシゲナーゼの精製と性質               
    Jun. 1986
  • マスフラグメントメトリーによるロイコトリエンB4及びプロスタグランジンの微量定量               
    Jul. 1985

Affiliated academic society

  • Feb. 2024 - Present
    Sigma Xi               
  • The Molecular Biology Society of Japan               
  • American Society for Biochemistry and Molecular Biology               
  • The Japanese Conference on the Biochemistry of Lipids               
  • The Japanese Biochemical Society               

Research Themes

  • Stress-relieving effects of acupuncture using salivary components as an indicator
    Grant-in-Aid for Challenging Research (Exploratory)
    Kochi University
    Jun. 2022 - Mar. 2025
  • 小児特有の化学物質複合曝露メカニズム解明とリスク管理モデルの提案               
    Apr. 2017 - Mar. 2020
  • Studies on G protein-coupled receptor controlling cell cycle and stemness
    Grant-in-Aid for Scientific Research (B)
    Gunma University
    Apr. 2012 - Mar. 2017
    G2A is a G protein-coupled receptor that uses oxidized free fatty acids as ligands. The addition of oxidized free fatty acids such as 9-HODE to the cultured cells resulted in cell cycle arrest. G2A induction was also observed by stress stimulation such as glucose starvation and hypoxia. It became clear that G2A induction is deeply involved in changes in intracellular pH and glutathione concentration. When glioma cells expressing G2A were transplanted into immunodeficient mice, tumor-formation and metastasis to the organs was observed. Immunohistochemical analysis of metastatic lesion revealed that epithelial mesenchymal transition occurred.
    Thus, G2A, a stress-inducible GPCR, stops the cell cycle in response to oxidized free fatty acids. On the other hand, G2A increases stemness in tumor cells resulting in epithelial mesenchymal transition and forms metastatic foci.
  • Analysis of receptor signaling in living cells by surface plasmon resonance
    Grant-in-Aid for Challenging Exploratory Research
    Gunma University
    Apr. 2011 - Mar. 2014
    Various methods have been used for the analysis of intracellular signaling from cell membrane receptors. However, there are problems in the reproducibility and operability. Previously, we have succeeded in measuring the SPR (surface plasmon resonance) through GPCR (G-protein coupled receptor) in living cells. In this study, we elucidated the part of the intracellular signaling pathways of GPCR signal using various inhibitors. Furthermore, we succeeded in measuring the SPR though RTKs (tyrosine kinase receptors), another group of membrane receptors. We also observed SPR signal through GPCR using a small portable SPR device.
  • 生体調節シグナルの統合的研究               
    Apr. 2007 - Mar. 2012
  • Functional analysis and its application of a G-protein coupled receptor, whose ligands are oxidized free fatty acids
    Grant-in-Aid for Scientific Research (B)
    Gunma University
    Apr. 2006 - Mar. 2008
    A purpose of this study was to clarify the physiological and pathological functions of a G-protein coupled receptor called G2A, and was to investigate the basic aspects of G2A signaling to establish new diagnosis / therapy. G2A is a receptor which ligands are oxidative flee fatty acids such as 9-HODE and 11-HETE derived from linoleic acid or arachidonic acid, respectively. It was reported that G2Awas induced by various DNA damage stimulation and its stimulation causes arrest of cell cycle. However, the physiological function of G2Awas unidentified.
    As skin is routinely and pathologically exposed to many oxidative stresses such as UV radiation, chemical agents, and inflammation that might induce both G2A expression and production of G2A ligands, we examined G2A fraction in human keratinocytes. G2A was expressed in human epidermis and normal human epidermal keratinocytes (NHEK). 9-HODE evoked intracellular calcium mobilization, and secretion of cytokines including IL-6, IL-8, and GM-CSF in NHEK cells. These responses became prominent in HaCaT cells, an immortalized human keratinocyte cell line, by overexpression of G2A. 9-HODE further inhibited proliferation of NHEK cells by suppressing DNA synthesis and arresting the cell cycle in the G0/1-phase, and down-regulation of G2A expression by small interfering RNA caused suppression of 9-HODE-induced effects on proliferation of NHEK cells 13-HODE, much weaker ligand of G2A, did not show any effects on either cytokine secretion and proliferation in NHEK cells. On the other hand, UVB and hydrogen peroxide induced G2A expression and caused oxidation of linoleate to produce 9-HODE in HaCaT cells.
    These results suggest that 9-HODE-G2A signaling plays proinflammatory roles in skin under oxidative conditions.
  • 生体情報の受容伝達と機能発現               
    Apr. 2002 - Mar. 2007
  • Roles and regulation of lipid mediators
    Grant-in-Aid for Scientific Research (A)
    The University of Tokyo
    Apr. 2000 - Mar. 2003
    Upon cell stimulation, various types of phospholipases are activated, and a class of lipid mediators are produced. They play important role in self-defense and maintenance of homeostasis. In the last three years, we have carried out biochemical and genetic experiments, and obtained results as follows. The results have been published in almost 50 original articles and 6 reviews or book chapters.
    1. Studies on cytosolic phospholipase A2 and related molecules.
    cPLA2α-null mice showed impairment in synaptic plasticity and reproduction. The enzyme also plays important roles in inflammatory bone resorption, autoimmune arthritis, acute respiratory distress syndrome (ARDS) and bleomycin-induce pulmonary fibrosis. Thus, a selective cPLA2a inhibitor would be beneficial for these disorders. In addition to a subtype of cPLA2, we also found β, and γ subtypes of the enzyme. While β-subtype has Ca-sensitive C2 domain, g-subtype is activated by reactive oxygen species. We also found a novel truncated isoforms of cPLA2, specifically expressed in dentate gyrus by stimulation.
    2. Characterization of leukotriene receptors.
    We identified 4 different types of leukotriene receptors (BLT1, BLT2, CysLT1, and CysLT2). They are differently expressed in cells and tissues, by cognate promoter activations. We elucidated detailed signal transduction of these receptors, and established cell, either overexpressing or lacking these receptors. More systematic phenotype analyzes will be done by gene targeting of the mice.
    3. Characterization of other types of receptors.
    We analyzed PAF (platelet-activating factor) receptor, and further found that PAF is deeply involved in inflammatory responses, capacitation of sperm, and neuronal migration in cerebellar granular cells. We also identified the fate of PAF (its breakdown to lysophospholipids, and reacylation to 1-alky1-phospholipids). By SNP analyzes, we found a novel mutation in the third intracellular domain in asthmatic family.
  • Analysis of mechanisms of neutrophil accumulation in the lung ; research utilizing LTB_4 receptor-expressed CHO cells.
    Grant-in-Aid for Scientific Research (C)
    University of Tokyo
    Apr. 1999 - Mar. 2001
    1. Determination of optimal condition of labeling LTB_4 receptor-expressed CHO cells with fluorescent probes.
    CHO cells could be adequately labeled for visualization with fluorescent microscopy with 4 micro molar CMFDA or 2 micro molar CMTMR.LTB_4 receptor-expressed CHO cells labeled with this conditions showed the same chemotaxis against LTB_4 as unlabeled cells in chemotaxis assay using chemotaxis chamber.
    2. Evaluation of neutrophil accumulation in mice lung with intratracheal administration of various agents and its reproducibility.
    As models of neutrophil accumulation in mice lung, we administered LTB_4, bleomycin, and silica intratracheally. After 4 hours of LTB_4 administration, neutrophilia over 10% in bronchoalveolar lavage fluid (BALF) cells were observed in only about 20% of examined mice, and after 24 hours of bleomycin administration, neutrophilia over 50% were observed in only about 50% of examined mice, suggesting that the reproducibility of neutrophil accumulation in mice lung by these methods was not adequate. In case of administration of silica, when silica was recovered in BALF, there were consistent marked neutrophilia (40-80%) in BALF cells 24 hours after silica administration, but, when silica was not recovered in BALF, neutrophilia were not observed. This findings indicated that expectoration and inaccessibility to lung parenchyme of intratracheally administered agents were the main cause of inadequate reproducibility of the procedures. Silica was a suitable agent for intratracheal administration in that its deposition into lung parenchyme could be verified by BALF analysis.
    3. in vivo Chemotaxis assay in mice model of intratracheal administration of silica using CMFDA-labeled LTB_4 receptor-expressed CHO cells.
    CMFDA-labeled LTB_4 receptor-expressed CHO cells and CMTMR-labeled control CHO cells were injected to mice intravenously via tail veins after 20 hours of intratracheal administration of silica. However, in BALF obtained 4 hours later, neither CMTMR nor CMFDA-labeled cells could not be recovered. Because there was a possibility that LTB_4 receptor-expressed CHO cells was not present freely in alveolar space but attached to pulmonary capillary endothelium or alveolar epithelium, we made histological specimens of lung tissues and examined fluorescent probe-labeled cells, but, at present, we could not obtain any definite results.
  • INVOLVEMENT OF LIPID MEDIATORS IN INFLAMMATORY DISORDERS
    Grant-in-Aid for Scientific Research (C)
    Apr. 1999 - Mar. 2001
    Lipid mediators such as leukotrienes (LTs) and platelet-activating factor (PAF) are major chemical mediators involved in inflammatory and allergic disorders. To clarify the pathological roles of these mediators in inflammatory disorders, this research project was carried out, and following results were obtained.
    1. Establishment and analysis of inflammatory animal model
    In PAF receptor transgenic mice, PAF receptor deficiency mice, cPLA2 deficiency mice, and wild-type mice, ARDS (adult respiratory distress syndrome) models were made by intratracheal administration of acid or intravenous administration of LPS, and analyzed. The obtained results indicate that PAP and cPLA2-dependent mediators play important roles in these conditions.
    PAF receptors are overexpressed in Kupffer cells after experimental hepatectomy in rat.
    2. Study on LTB4 receptor
    The mechanism of leukocyte-specific expression of LTB4 receptor was revealed by its promoter analysis. Using in vivo chemotaxis of CHO cells expressing LTB4 receptor, the possible roles of LTB4 in pathogenesis of acute renal inflammation were indicated. The second receptor for LTB4 was discovered. The project on establishment of LTB4 deficiency mice is now in progress.
    3. Signal transduction through LTD4 receptor
    Intracellular signal transduction through LTD4 receptor was analyzed in monocytes and macrophages.
    4. Intracellular localization of enzymes involved in production of lipid mediators
    The mechanisms of intracellular localization and translocation of enzymes such as cPLA2, 5-lipoxygenase and LTA4 hydrolase were studied.
    These results revealed that mechanisms of lipid mediator production and pathological roles of lipid mediators in inflammatory disorders, and may help us develop new therapies and drugs.
  • FUNCTIONAL REGULATION OF RECEPTORS FOR LIPID MEDIATORS
    Grant-in-Aid for Scientific Research (B)
    The University of Tokyo
    Apr. 1998 - Mar. 2000
    Lipid mediators such as leukotrienes (LTs) and platelet-activating factor (PAF) are major chemical mediators involved in inflammatory and allergic disorders. Despite their potent biological activities, little is known about the function and translational regulation of their receptors. To clarify these questions, we carried out following experiments and obtained some results that may contribute better understanding of patho-physiological roles of lipid mediators and development of new therapies and drugs for inflammatory and at11ergic disorders.
    1. We analyzed the mechanisms of ligand-induced internalization of PAP receptors.
    2. Using PAP receptor knockout mice and cPLA2 knockout mice, the roles of lipid mediators in acute lung injuries occurred by LPS and acid were investigated.
    3. Functional coupling of LTB4 receptor with G-proteins in porcine WBC was identified.
    4. Analysis of human genome for LTB4 receptor was carried out. The mechanisms for leukocyte specific expression of LTB4 receptor was clarified.
    5. cDNA clones for LTB4 receptors of mouse, rat and Guinea pig were identified. And their functions were analyzed.
    6. We analyzed the signal transduction mechanisms through LTD4 receptors using human monocytic leukemia THP-1 cells.
  • MECHANISM OF NEURONAL DEATH AND REGENERATION
    Grant-in-Aid for Scientific Research (B)
    THE UNIVERSITY OF TOKYO
    Apr. 1998 - Mar. 2000
    Neuronal survival and death are determined by multiple factors including neuronal activity as well as an influence from surrounding glia. In this project, we focus on various lipid mediators in terms of its ability of interaction between neuron and glia. We found that various lipid mediators are produced by stimuli, and play roles in the network as follows. LPA, produced by various cells, stimulates growth and cell maturation of neuron as well as proliferation of astrocytes. LPA also releases various cytokines and neurotrophis (NGF, BDNF) from astroglia, which activates neuronal cells. PAP is released from neuron by the NMDA stimulation, and acts on microglia. Microglia produces NO, and causes chemotaxis towards neuron, suggesting the role of microglia for repairing neuronal cells. PAF receptor-deficient mice and phospholipase A2 (cPLA2)-deficient mice are established, and their congenic mice are now available by backcrossing. The exact roles of these lipid mediators will be clarified by extensive analyses of their phenotypes.
  • IN VIVO AND INTRACELLULAR ROLES OF LEUKOTRIENE B4 RECEPTOR.
    Grant-in-Aid for Scientific Research (C)
    UNIVERSITY OF TOKYO
    1999 - 2000
    To investigate the biological functions of leukotriene B4 receptor in vivo, we established a line of mice deficient in high-affinity leukotriene B4 receptor (BLT1). Embryonic stem (ES) cells were transfected with a targeting vector for BLT1, and several clones were isolated and confirmed for their homologous recombination by Southern blotting. These ES cells were microinjected to blastcysts, transferred to pseudopregnant female mice, and subsequently chimeric mice were obtained. These chimeric mice are crossed among them, and finally BLT1-deficient mice were born. Now these mice are under backcrossing to examine their phenotype.
    CHO cells stably expressing BLT1 showed robust chemotaxis toward LTB4 in vitro, so we tried to examine the chemotactic activities of these cells in vivo. Rat acute ischemic-reperfusion renal injury was initiated by 45 minute-clamping of the renal artery. After 24 hrs, cells were injected into the injured kidney, and were allowed to chemotax for 4 hrs. Only in case of ischemic kidney, not in the sham-operated kdney, CHO cells expressing BLT1 migrated into the peritubal portion of the kidney. Control cells transfected with empty vector did not migrate at all. Prefeeding of the rats with BLT antagonist (Ono 4057) not only inhibited the cells migration, but also reduced the severity of the renal failure, suggesting that LTB4-BLT1 interaction plays important roles in the initiation and the progression of ischemic renal failure.(Noiri, E., et al Proc.Natl.Acad.Sci.U.S.A., 2000)
    To clarify the molecular mechanisms of the cell-specific expression of BLT1, we examined the transcriptional regulation of BLT1. BLT1 gene is a small gene within 4 kbps, and its promoter contains no TATA-box, but an Initiator sequence. Serial deletion analyses revealed that Sp-1 at-50 from the initiation site plays a pivotal role in BLT1 transcription. Moreover, the promoter region was totally methylated in BLT1-nonexpressing cells, but not in the expressing cells. In vitro methylation of BLT1 promoter almost completely inhibited its promoter activity.(Kato, K., et al.J.Exp.Med.2000)
    On the course of analyzing BLT1 promoter, we found a novel gene with structural similarities with BLT1. The encoded protein was a novel G-protein-coupled receptor, and exhibited a low-affinity, but significant binding to LTB4. This receptor efficiently transduces intracellular signaling toward calcium increase, inhibition of ademylyl cyclase, and chemotaxis by application of LTB4, thus we named it a second LTB4 receptor, BLT2.(Yokomizo, et al.J.Exp.Med.2000, Yokomizo, T.et al.J.Biol.Chem.2001)
  • Molecular Cloning and Signal Transduction of Leukotriene Receptors
    Grant-in-Aid for Scientific Research (C)
    The University of Tokyo
    Apr. 1997 - Mar. 1999
    Leukotrienes are major lipid mediators involved in inflammatory and allergic disorders. Despite their potent biological activities, little is known about the receptors and intracellular signaling pathways.
    1.We cloned a cDNA for a LTB_4 receptor (BLT) from HL-60 cells differentiated with retinoic acid using a subtraction strategy. The open reading frame (ORF) of the cDNA encodes a protein of 352 amino acids and is predicted to contain seven membrane-spanning domains. In CHO cells stably expressing BLT, LTB_4 elicited many signal transductions such as increase in intracellular calcium, InsP_3 accumulation, and inhibition of adenylyl cyclase. The CHO cells revealed a marked chemotactic response toward nM order of LTB_4. Calcium increase and InsP_3 accumulation induced by LTB_4 were partially sensitive to pertussis toxin (PTX), while chemotaxis and inhibition of adenylate cyclase were completely sensitive to PTX, indicating that BLT transduces LTB_4 signals through both PTX-sensitive and -insensitive G proteins.
    2.We analyzed the signal transduction mechanisms through LTD_4 receptors using human monocytic leukemia THP-1 cells. When these cells were stimulated with LTD_4, intracellular calcium concentration was increased and mitogen-activated protein kinase (MAP kinase) was activated. A chemotactic response of THP-1 cells toward LTD_4 was also observed. We found that LTD_4 has at least two distinct signaling pathways in THP-1 cells, a PTX-insensitive mitogen-activated protein kinase activation through protein kinase Calpha and Raf-1 and a PTX-sensitive chemotactic response. This cellular signaling can explain in part the versatile activities of LTD_4 in macrophages under inflammatory and allergic conditions.
  • Elucidation of roles of platelet-activating factor receptor by gene targeting.
    Grant-in-Aid for Scientific Research (B)
    University of Tokyo
    Apr. 1996 - Mar. 1998
    Platelet-activating factor (PAF) is a potent phospholipid mediator involved in inflammatory and allergic responses. It is also reported that PAF plays major roles in endotoxin-induced lethality, reproduction and brain development. To determine the role of PAF and its receptor in vivo, we generated a PAF receptor-deficient mice, by honologous recombination. Offspring were obtained with a Menderian distribution. They grow up normally, and no developmental changes are observed in any organs examined. The level of blood immunoglobulins and differential cell counts show no abnormality.
    When the mice were sensitized and challenged with ovalbumin, the wild type mice showed a marked bronchial constriction, pulmonary edema, hypotension and death. On the other hand, the PAF receptor-deficient mice showed only moderate response to these treatments. Upon challenging with endotoxin, no significant difference was observed in both groups. Thus, we concluded that PAF is deeply involved in anaphylactic responses, while it shows minor role in the endotoxin-induced pathologies and lethality. Considering PAF antagonists show some protective effects on endotoxin-shock, even in PAF receptor knock-out mice, there may exist other targets of PAF receptor antagonists to protect the living system from endotoxin-induced disorders.
  • Pathophysiology and Treatment of Endotoxin Shock
    Grant-in-Aid for Scientific Research (A)
    University of Tokyo
    Apr. 1995 - Mar. 1997
    Endotoxin causes systemic collapse, disseminated intravascular coagulation and lethality, by infection of gram-negative bacteria. Although many reports the production of cytokines, the precise mechanism of pathophysiological events remained obscure. By cell biology and molecular biology techniques, we obtained following results.
    (1) Elucidation of relation between endotoxin and PAF receptor
    We established transgenic mice overxpressing PAF receptor. These mice showed severe symptoms of endotoxin shock and death by intravenous administration of small doses of LPS.The lethality was efficiently blocked by the use of PAF receptor antagonists, suggesting that PAF-PAFR is involved in the pathogenesis of endotoxin-induced lethality.
    (2) Elucidation of LPS action on macrophages
    By incubating of macrophages with bacterial endotoxin, PAFR mRNA was increased several fold after 4h. MAP kinase was also activated, and the activation related to the tyrosine phosphorylation of Raf-1 kinase.
  • STUDIES ON PHYSIOLOGICAL FUNCTION OF PLATELET-ACTIVATING FACTOR
    Grant-in-Aid for General Scientific Research (B)
    THE UNIVERSITY OF TOKYO
    Apr. 1993 - Mar. 1995
    Following results were obtained on the physiological role and cellular signaling of platelet-activating factor (PAF).
    (1)Cellular signaling via PAF receptor
    By using transfected receptor in CHO cells, cellular signaling after PAF application was determined. PAF stimulates phosphoinositide turnover, mitogen-activated protein (MAP) kinase, phospholipase A2, and inhibits adenylate cyclase. From the results of PTX-treatment, PAF receptor appears to couple with two types of G-proteins. Ca-independent activation of MAP kinase was inhibited by wortmannin, suggesting a wortmannin-sensitive molecule such as phosphatidylinositol 3-kinase is present between Gi and MAP kinase.
    To determine the molecular mechanisms of signal desensitization by PAF,we prepared CHO cells carrying wild-type, C-terminal deletion mutant, and substitution mutant (Ser, Thr to Ala) receptors. We found that C-terminal cytoplasmic tail is not required for forward signal transduction, but it is essential for signal-shut down. A family of GRK (G-protein receptor kinase) may be involved in the phosphorylation of Ser/Thr residues leading to signal shut down.
    (2)Genomic structure of PAF receptor.
    Human PAF receptor gene is present as a single copy in haploid on the chromosome 1q. The gene consists of three exons, separated each other > 20kb intron. Two5'-noncoding exons has distinct transcriptional start site, and promoters. These exons are alternatively spliced to a common splice acceptor to yield two different mRNAs. Transcript 1 is present in almost all tissues, and up-regulated by PAF or endotoxin through its NF-kB site. Transcript 2 is expressed in more tissue-specific way, and up-regulated by estrogen, and down-regulated by TGF-b. The physiological and pathological significance of these promoters are currently under investigation.
  • THE MECHANISM AND BIOSYNTHESIS OF BIOACTIVE LIPIDS
    Grant-in-Aid for General Scientific Research (C)
    The University of Tokyo
    Apr. 1992 - Mar. 1994
    1. STUDY FOR LEUKOTRIENE BIOSYNTHESIS AND METABOLISM
    A monoclonal antibody to LTC_4 synthase was developed, and using this antibody enzyme purification is now going on.
    A mutagenesis study of LTA_4 hydrolase revealed that the active center for LTB_4 producing activity is different from that for aminopeptidase activity.
    We showed that LTB_4 is inactivated by LTB_4-12-hydroxydehydrogenase in porcine kidney, and this enzyme was purified to apparent homogeneity.
    2. STUDY FOR FUNCTION OF LEUKOTRIENE
    Studies for cDNA cloning of leukotriene receptors are going on using frog oocyte expression system or mammalian cell expression system.
    3. STUDY FOR PAR RECEPTOR
    The presence of functionally active PAF receptor in rat brain have been indicated.
    In a human eosinophilic leukemia cell line (EoL-1 cells), PAF receptor were induced during differentiation by sodium butyrate.
    Studies on human PAF receptor gene revealed that two different promoter exist to produce two types of mRNA, namely leukocyte type and heart type.
    In CHO cells transfected with PAF receptor, PAF activated MAP kinase and MAP kinase kinase.
  • Screening and Development of New Immnomodulatory Drugs using PAF Receptor Gene as a Probe
    Grant-in-Aid for Developmental Scientific Research (B)
    The University of Tokyo
    Apr. 1991 - Mar. 1993
    Platelet-activating factor (PAF) is a potent mediator of inflammation, immunological disorders, and endotoxin shock. We have recently isolated cDNA clones of human and guinea pig PAF receptors. Using these clones as probe, we have obtained following results.
    1. Isolation and structure of PAF receptor gene.
    PAF receptor gene is consisted of three exons which are separated by >20kb introns. All exons are localized on chromosome 1. By alternative splicing, the leukocyte- and heart-type transcripts are produced. They have differentially regulated by distinct promoters.
    2. Elucidation of signal transduction through a cloned PAF receptor.
    A stable transfectant cell (CHO) was established carrying a cloned PAF receptor. By the application of PAF, phospholipase C and A_2, and MAP (mitogen-associated protein) are all activated, while adenylate cyclase was inhibited. These cellular events appear to be regulated by different types of G-proteins. Furthermore, we found that endotoxin. LPS, stimulated PAF receptor and yielded a Ca increase in human platelets as well as CHO transfectants. Thus, a part of LPS signaling, especially that related to platelet-aggregation might be due to the direct activation of PAF receptor.
    3. Development of Screening System of PAF Receptor Agonists and Antagonists.
    PAF receptor was expressed in Xenopus oocytes and a sensitive assay system of PAF receptor agonists/antagonists was made. Furthermore, COS cells/CHO cells carrying an excess amount of PAF receptors were constructed. By using membrane fractions of these cells, the highly specific screening system of PAF receptor modulator (either receptor antagonists or uncoupler of receptor-G-protein) was established. Through screening of naturally-occurring and synthetic compounds, several candidate chemicals have been obtained, which have potentiality for immunomodulatory drugs.
  • Studies on Leukotriene Biosynthesis and Signal Transduction.
    Grant-in-Aid for General Scientific Research (B)
    The University of Tokyo
    1990 - 1992
    PAF and leukotrienes are lipid mediators involved in inflammatory/allergic response as well as various cardiovascular and immunological disorders. We have carried out experiments on biosyntheses and signal transduction of these lipid mediators.
    1. Isolation of PAF and leukotriene receptors.
    By expression cloning using Xenopus oocyte system, we isolated a cDNA of PAF receptor as the first successful example of receptor cloning of lipid mediators. A human homologue was also obtained. They are composed of 342 amino acid residues with putative seven transmembrane spanning domains. These receptors were expressed in COS cells or CHO cells, and cellular signalings are extensively studied. It was shown that PAF receptor couples to phospholipases, adenylate cyclase, and MAP kinase via different types of G- proteins. Leukotriene receptors (B4, and D4) were solubilized from guinea pig leukocyte and lung membrane, respectively in an active form. They activate phospholipase A_2 and C via Gi proteins. Molecular cloning of these receptors by two strategies (protein purification and expression cloning) is currently ongoing.
    2. Leukotriene A_4 hydrolase. a bifunctional enzyme.
    Leukotriene B_4, a potent chemotactic factor, is produced by an enzyme termed leukotriene A4 hydrolase. By cDNA cloning and elucidation of the primary structure of the enzyme have shown that the enzyme is highly homologous to various types of metalloproteinases. In fact, it was shown that the enzyme contains a zinc ion, which is essential for both intrinsic aminopeptidase activity and leukotriene A_4 hydrolase. To determine the active site of the enzyme, site-directed mutagenesis experiments were performed. The mutation of His-296, or Glu-315 yielded loss of zinc ion with concomitant disappearance of both enzyme activities. However, by changing Glu-297 to other amino acids. two enzyme activities were clearly separated. The mechanism of incorporation of water molecule as well as the physiological significance of bifunctional role of enzyme remain unclear.

Industrial Property Rights

Social Contribution Activities

  • 医師養成のグランドデザイン検証ワーキンググループ 座長               
    others
    May 2016 - May 2018
  • 世界脳週間               
    lecturer
    Apr. 2002 - Apr. 2017

■University education and qualification information

Qualifications, licenses

  • 20 May 1977
    Medical License, Medical License