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Distribution analysis of S1P on tissue sections by high resolution MS imaging

Research Project

Project/Area Number 20H03374
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
Research InstitutionTeikyo University (2021-2022)
Tohoku University (2020)

Principal Investigator

Saigusa Daisuke  帝京大学, 薬学部, 准教授 (90545237)

Co-Investigator(Kenkyū-buntansha) 可野 邦行  東京大学, 大学院薬学系研究科(薬学部), 助教 (50636404)
松本 洋太郎  東北大学, 薬学研究科, 講師 (90420041)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2022: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2020: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
KeywordsS1P / MALDI / MSイメージング / 質量分析計 / スフィンゴ脂質 / MSイメージング法 / 一細胞 / 誘導体化
Outline of Research at the Start

スフィンゴシン一リン酸(S1P)は、生理活性脂質の一種であり、生体内における免疫機能の制御への関連が明らかにされている。また、がんを含む病気の発症にも関わることから、S1Pシグナル伝達系に含まれる分子機構の解明による創薬標的分子の同定が期待されている。しかしながら、これまでに生体組織を用いたS1Pの機能解析において、細胞分布を組織切片上で直接可視化することはできなかった。
本研究は、我々が開発した質量分析イメージング法によるS1P可視化法を一細胞レベルの解析技術に発展させ、S1Pの分子機能解析に応用することで新たな創薬標的の同定し、未来型医療に貢献する成果を創出することを目的としている。

Outline of Final Research Achievements

Sphingosine monophosphate (S1P) is a bioactive lipid and has been implicated in the pathogenesis of immunological diseases, cancer, and atherosclerosis. S1P and its related molecules expressed in their signaling pathway are considered potential drug targets. However, it has been difficult to visualize the tissue distribution of S1P using conventional analytical methods. In this study, we developed a S1P-specific detection method and a highly sensitive and high-resolution tissue section by MS imaging. We constructed a library of Phostag derivatization reagents by synthesizing novel Phostag derivatization reagents, and succeeded in highly sensitive detection of S1P.

Academic Significance and Societal Importance of the Research Achievements

我々は、S1Pを高感度に検出できる新規Phostag試薬の合成に成功した。本研究では、Phostag誘導体化試薬を複数種合成したことにより、Phostagライブラリーを構築したが、この試薬類は様々な化合物に対して応用できる可能性が考えられるため、学術的な意義が高い。また、S1P関連疾患に対する分子メカニズム解析にも有用であり、疾患解明に貢献するため社会的意義が高いと考えられる。本研究により新たな創薬に役立つことが期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (31 results)

All 2023 2022 2021 2020

All Journal Article (18 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 18 results,  Open Access: 18 results) Presentation (11 results) (of which Int'l Joint Research: 4 results,  Invited: 7 results) Book (2 results)

  • [Journal Article] Decreased β-hydroxybutyrate and ketogenic amino acid levels in depressed human adults2023

    • Author(s)
      Sato Shiho、Yu Zhiqian、Sakai Mai、Motoike Ikuko N.、Saigusa Daisuke、Hirayama Ryo、Kikuchi Yoshie、Abe Takaaki、Kinoshita Kengo、Koshiba Seizo、Tomita Hiroaki
    • Journal Title

      European Journal of Neuroscience

      Volume: 57 Issue: 6 Pages: 1018

    • DOI

      10.1111/ejn.15931

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiomics and artificial intelligence enabled peripheral blood-based prediction of amnestic mild cognitive impairment2023

    • Author(s)
      Tatara Y, Yamazaki H, Katsuoka F, Chiba M, Saigusa D, Kasai S, Nakamura T, Inoue J, Aoki Y, Shoji M, Motoike I, Tamada Y, Hashizume K, Shoji M, Kinoshita K, Murashita K, Nakaji S, Yamamoto M, Itoh K.
    • Journal Title

      Current Research in Translational Medicine.

      Volume: 71 Issue: 1 Pages: 103367-103367

    • DOI

      10.1016/j.retram.2022.103367

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lipidomic and metabolic profiling of plasma and plasma-derived extracellular vesicles by UHPLC-MS/MS2022

    • Author(s)
      Daisuke Saigusa、Takeshi Honda、Yuko Iwasaki、Koji Ueda、Eiji Hishinuma、Naomi Matsukawa、Akira Togashi、Noriyuki Matsutani、Nobuhiko Seki
    • Journal Title

      Medical Mass Spectrometry

      Volume: 6 Issue: 2 Pages: 126-137

    • DOI

      10.24508/mms.2022.11.007

    • ISSN
      2432-7441, 2432-745X
    • Year and Date
      2022-11-25
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantification of threonine-containing lysophospholipids using ESI-LC-MS/MS in mouse tissues2022

    • Author(s)
      Michiyo Okudaira、Kuniyuki Kano、Kumiko Makide、Daisuke Saigusa、Tomohiko Ohwada、Junken Aoki
    • Journal Title

      Medical Mass Spectrometry

      Volume: 6 Issue: 2 Pages: 138-148

    • DOI

      10.24508/mms.2022.11.008

    • ISSN
      2432-7441, 2432-745X
    • Year and Date
      2022-11-25
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modulations of bioactive lipids and their receptors in postmortem Alzheimer’s disease brains2022

    • Author(s)
      Kurano Makoto、Saito Yuko、Uranbileg Baasanjav、Saigusa Daisuke、Kano Kuniyuki、Aoki Junken、Yatomi Yutaka
    • Journal Title

      Frontiers in Aging Neuroscience

      Volume: 14 Pages: 1066578-1066594

    • DOI

      10.3389/fnagi.2022.1066578

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Plasma metabolic disturbances during pregnancy and postpartum in women with depression2022

    • Author(s)
      Z Yu, N Matsukawa, D Saigusa, I. N. Motoike, C Ono, Y Okamura, T Onuma, Y Takahashi, M Sakai, H Kudo, T Obara, K Murakami, M Shirota, S Kikuchi, N Kobayashi, Y Kikuchi, J Sugawara, N Minegishi, S Ogishima, K Kinoshita, M Yamamoto, N Yaegashi, S Kuriyama, S Koshiba, H Tomita
    • Journal Title

      iScience

      Volume: 25 Issue: 12 Pages: 105666-105666

    • DOI

      10.1016/j.isci.2022.105666

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dynamic modulations of urinary sphingolipid and glycerophospholipid levels in COVID-19 and correlations with COVID-19-associated kidney injuries2022

    • Author(s)
      Kurano Makoto、Jubishi Daisuke、Okamoto Koh、Hashimoto Hideki、Sakai Eri、Morita Yoshifumi、Saigusa Daisuke、Kano Kuniyuki、Aoki Junken、Harada Sohei、Okugawa Shu、Doi Kent、Moriya Kyoji、Yatomi Yutaka
    • Journal Title

      Journal of Biomedical Science

      Volume: 29 Issue: 1 Pages: 1069-1087

    • DOI

      10.1186/s12929-022-00880-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Codon Usage and mRNA Stability are Translational Determinants of Cellular Response to Canonical Ferroptosis Inducers2022

    • Author(s)
      Rashad Sherif、Byrne Shane R、Saigusa Daisuke、Xiang Jingdong、Zhou Yuan、Zhang Liyin、Begley Thomas J、Tominaga Teiji、Niizuma Kuniyasu
    • Journal Title

      Neuroscience

      Volume: 501 Pages: 103-130

    • DOI

      10.1016/j.neuroscience.2022.08.009

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Introducing the Lipidomics Minimal Reporting Checklist2022

    • Author(s)
      McDonald Jeffrey G.、Ejsing Christer S.、Kopczynski Dominik、他29名
    • Journal Title

      Nature Metabolism

      Volume: 4 Issue: 9 Pages: 1086

    • DOI

      10.1038/s42255-022-00628-3

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Metabolic and Epigenetic Regulation of SMAD7 by STC1 Ameliorates Lung Fibrosis2022

    • Author(s)
      Ohkouchi Shinya、Kanehira Masahiko、Saigusa Daisuke、Ono Manabu、Tazawa Ryushi、Terunuma Hideya、Hirano Taizou、Numakura Tadahisa、Notsuda Hirotsugu、Inoue Chihiro、Saito-Koyama Ryoko、Tabata Masao、Irokawa Toshiya、Ogawa Hiromasa、Kurosawa Hajime、Okada Yoshinori
    • Journal Title

      American Journal of Respiratory Cell and Molecular Biology

      Volume: 67 Issue: 3 Pages: 320

    • DOI

      10.1165/rcmb.2021-0445oc

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gene expression changes related to bone mineralization, blood pressure and lipid metabolism in mouse kidneys after space travel2022

    • Author(s)
      Suzuki Norio、Iwamura Yuma、Nakai Taku、Kato Koichiro、Otsuki Akihito、Uruno Akira、Saigusa Daisuke、Taguchi Keiko、Suzuki Mikiko、Shimizu Ritsuko、Yumoto Akane、Okada Risa、Shirakawa Masaki、Shiba Dai、Takahashi Satoru、Suzuki Takafumi、Yamamoto Masayuki
    • Journal Title

      Kidney International

      Volume: 101 Issue: 1 Pages: 92

    • DOI

      10.1016/j.kint.2021.09.031

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lysophosphatidic acid receptor<sub>1/3</sub> antagonist inhibits the activation of satellite glial cells and reduces acute nociceptive responses2022

    • Author(s)
      Hoshino Yoko、Okuno Toshiaki、Saigusa Daisuke、Kano Kuniyuki、Yamamoto Shota、Shindou Hideo、Aoki Junken、Uchida Kanji、Yokomizo Takehiko、Ito Nobuko
    • Journal Title

      The FASEB Journal

      Volume: 36 Issue: 4

    • DOI

      10.1096/fj.202101678r

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Urine autotaxin levels reflect the disease activity of sarcoidosis2022

    • Author(s)
      Murakami Koji、Tamada Tsutomu、Saigusa Daisuke、Miyauchi Eisaku、Nara Masayuki、Ichinose Masakazu、Kurano Makoto、Yatomi Yutaka、Sugiura Hisatoshi
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 4372-4372

    • DOI

      10.1038/s41598-022-08388-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of kit-based metabolomics with other methodologies in a large cohort, towards establishing reference values2021

    • Author(s)
      Saigusa D*, Hishinuma E, Matsukawa N, Takahashi M, Inoue J, Tadaka S, Motoike I N, Hozawa A, Izumi Y, Bamba T, Kinoshita K, Ekroos K, Koshiba S, Yamamoto M.
    • Journal Title

      Metabolites

      Volume: 11 Issue: 10 Pages: 652-652

    • DOI

      10.3390/metabo11100652

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nrf2 plays a critical role in the metabolic response during and after spaceflight2021

    • Author(s)
      Uruno A、Saigusa D、Suzuki T、Yumoto A、Nakamura T、Matsukawa N、Yamazaki T、Saito R、Taguchi K、Suzuki M、Suzuki N、Otsuki A、Katsuoka F、Hishinuma E、Okada R、Koshiba S、Tomioka Y、Shimizu R、Shirakawa M、Kensler TW.、Shiba D、Yamamoto M
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 1381

    • DOI

      10.1038/s42003-021-02904-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of an on-tissue derivatization method for MALDI mass spectrometry imaging of bioactive lipids containing phosphate monoester using Phos-Tag2021

    • Author(s)
      Iwama Taiga、Kano Kuniyuki、Saigusa Daisuke、Ekroos Kim、van Echten-Deckert Gerhild、Vogt Johannes、Aoki Junken
    • Journal Title

      Analytical Chemistry

      Volume: 93 Issue: 8 Pages: 3867

    • DOI

      10.1021/acs.analchem.0c04479

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of biomarkers to diagnose diseases and find adverse drug reactions by metabolomics2021

    • Author(s)
      Saigusa Daisuke、Matsukawa Naomi、Hishinuma Eiji、Koshiba Seizo
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 37 Pages: 100373-100373

    • DOI

      10.1016/j.dmpk.2020.11.008

    • NAID

      210000172800

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Filopodium-derived vesicles produced by MIM enhance the migration of recipient cells2021

    • Author(s)
      Tamako Nishimura*, Takuya Oyama*, Hooi Ting Hu*, Toshifumi Fujioka* et al.(*:equally contributed)
    • Journal Title

      Developmental Cell

      Volume: 56 Issue: 6 Pages: 842

    • DOI

      10.1016/j.devcel.2021.02.029

    • NAID

      120007172296

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 血漿およびエクソソーム由来代謝物分析手法開発と肺腺癌マーカー探索への応用2023

    • Author(s)
      三枝大輔、本田健、岩崎裕子、植田幸嗣、福内友子、山岡法子、副島研造、岸一馬、大熊裕介、富樫亮、松谷哲行、関順彦
    • Organizer
      第20回日本臨床腫瘍学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 宇宙環境における酸化ストレスがもたらす生体内脂質変動解析2022

    • Author(s)
      小池海斗、三枝大輔、宇留野晃、鈴木隆史、福内友子、山岡法子、芝大、山本雅之
    • Organizer
      第70回質量分析総合討論会
    • Related Report
      2022 Annual Research Report
  • [Presentation] UHPLC-FTMSによるヒト前房水を用いた緑内障バイオマーカー探索研究2022

    • Author(s)
      小暮瑞穂、佐藤孝太、藤岡周、國分太貴、吉田真彰、横山悠、福内友子、山岡法子、中澤徹、三枝大輔
    • Organizer
      第70回質量分析総合討論会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 生体内メタボローム解析技術開発と疾患バイオマーカー探索研究への応用2022

    • Author(s)
      三枝大輔
    • Organizer
      第47回日本医用マススペクトル学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Lipidomic Profiling in the Large-Scale Cohort for Biomarker Discovery and the Importance of Separation Science2022

    • Author(s)
      Daisuke Saigusa
    • Organizer
      Gordon Research Conference, Lipidomics
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 疾患関連リゾリン脂質の高精密定量を目的とした分離分析系の開発について2021

    • Author(s)
      三枝大輔、青木淳賢
    • Organizer
      第32回クロマトグラフィー科学会議
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Addressing accuracy of reference values in a large-scale cohort by MS-based metabolomics2021

    • Author(s)
      Daisuke Saigusa
    • Organizer
      VPAP
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Evaluation for quantified values of lipidomic profiling in a large-scale cohort2021

    • Author(s)
      Daisuke Saigusa
    • Organizer
      iSLS10
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 質量分析イメージングの高感度検出に向けた研究2021

    • Author(s)
      三枝大輔、青木淳賢
    • Organizer
      第74回イオン反応研究部会講演会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 質量分析イメージングによる疾患バイオマーカーの機能評価に関する研究2021

    • Author(s)
      三枝大輔
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] The utility of conductive adhesive film for the distribution analysis of small molecule by MALDI-MSI2020

    • Author(s)
      Daisuke Saigusa
    • Organizer
      24h-IMSI
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] Mass Spectrometry for Lipidomics: Methods and Applications2022

    • Author(s)
      Michal Holcapek, Kim Ekroos
    • Total Pages
      752
    • Publisher
      WILEY
    • ISBN
      9783527836505
    • Related Report
      2022 Annual Research Report
  • [Book] メタボロミクス実践ガイド2021

    • Author(s)
      馬場 健史、平山 明由、松田 史生、津川 裕司
    • Total Pages
      334
    • Publisher
      羊土社
    • ISBN
      9784758122511
    • Related Report
      2021 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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