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Development of tree-dimensional MS imaging for sphingolipids

Research Project

Project/Area Number 17K08233
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Physical pharmacy
Research InstitutionTohoku University

Principal Investigator

Saigusa Daisuke  東北大学, 東北メディカル・メガバンク機構, 講師 (90545237)

Co-Investigator(Kenkyū-buntansha) 可野 邦行  東北大学, 薬学研究科, 助教 (50636404)
元池 育子  東北大学, 東北メディカル・メガバンク機構, 准教授 (70347178)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsスフィンゴ脂質 / MALDI / MSイメージング / 質量分析計 / S1P / 凍結組織切片 / 粘着性導電性フィルム / イメージングMS / 組織切片 / 立体可視化 / DESI / DIUTHAME / IMS / スフィンゴシン一リン酸 / イオンモビリティ / イメージング MS / LC-MS/MS / 肝癌
Outline of Final Research Achievements

Sphingolipids are bioactive lipid mediators related with the expression of cancer and immune disease and has been estimated the target molecules of drug discovery. Although their biological functions were reacted beside on the metabolism-related molecules on tissue, they could not be detected directly on the tissue section in previous studies. In this study, we demonstrated that the conductive adhesive film can overcome the setbacks of the MALDI-MSI approach by allowing the imaging of intact cryosections, such as the bone, muscle, adipose tissues and whole mouse body. We finally developed the on-tissue derivatization method for the detection of S1P on the cryosection and improved the ion intensities of sphingolipids by means of the MALDI-MSI analysis.

Academic Significance and Societal Importance of the Research Achievements

スフィンゴ脂質の一種であるS1Pは、脂質メディエーター機能が注目されているにも関わらず、これまでに組織切片上で直接検出することはできなかったため、研究の大きな障壁となっていた。我々は、世界で初めてMALDI-MSイメージングによるS1Pの可視化に成功したことから、今後のS1Pを標的とした基礎研究および創薬開発に大きな発展をもたらすことから、極めて社会的意義が高い。また、導電性粘着フィルムは、S1Pやスフィンゴ脂質のみならず各種代謝物について、これまでに凍結切片作成が困難であった組織におけるMALDI-MSIによる解析が可能になることから学術的な意義は極めて高い。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (38 results)

All 2020 2019 2018 2017

All Journal Article (15 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 15 results,  Open Access: 14 results) Presentation (21 results) (of which Int'l Joint Research: 5 results,  Invited: 14 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Identification of novel biomarkers of hepatocellular carcinoma by high-definition mass spectrometry: class FormattedString { value: Ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry and desorption electrospray ionization mass spectrometry imaging }2020

    • Author(s)
      Nagai, K. et al. Koshiba S. et al. Tomioka Y.(合計17名、本研究者は14番目)
    • Journal Title

      Rapid Commun Mass Spectrom.

      Volume: 34 Issue: S1

    • DOI

      10.1002/rcm.8551

    • URL

      https://localhost/en/publications/83435901-1a6c-4eee-a51b-d81803406d32

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Measurement of the Spatial Distribution of S1P in Small Quantities of Tissues: Development and Application of a Highly Sensitive LC-MS/MS Method Combined with Laser Microdissection2019

    • Author(s)
      Wang Jiao、Kano Kuniyuki、Saigusa Daisuke、Aoki Junken
    • Journal Title

      Mass Spectrometry

      Volume: 8 Issue: 1 Pages: A0072-A0072

    • DOI

      10.5702/massspectrometry.A0072

    • NAID

      130007594456

    • ISSN
      2186-5116, 2187-137X
    • URL

      https://pure.teikyo.jp/en/publications/8567d236-2505-42f2-9af3-b5e050b96555

    • Year and Date
      2019-02-14
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Conductive Adhesive Film Expands the Utility of Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging2019

    • Author(s)
      Saigusa D, Saito R, Kawamoto K, Uruno A, Kano K, Aoki J, Yamamoto M, Kawamoto T.
    • Journal Title

      Anal Chem

      Volume: 91 Issue: 14 Pages: 8979

    • DOI

      10.1021/acs.analchem.9b01159

    • URL

      https://pure.teikyo.jp/en/publications/406db461-55fa-483a-af5a-da88f49e1776

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Alteration of the lysophosphatidic acid and its precursor lysophosphatidylcholine levels in spinal cord stenosis: A study using a rat cauda equina compression model2019

    • Author(s)
      Uranbileg B, Ito N, Kurano M, Saigusa D, Saito R, Uruno A, Kano K, Ikeda H, Yamada Y, Sumitani M, Sekiguchi M, Aoki J, Yatomi Y.
    • Journal Title

      Scientific reports

      Volume: 9 Issue: 1 Pages: 16578-16578

    • DOI

      10.1038/s41598-019-52999-5

    • URL

      https://pure.teikyo.jp/en/publications/35fd44a1-252a-4f28-a3e0-48245ce26103

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Value of global metabolomics in association with diagnosis and clinicopathological factors of renal cell carcinoma2019

    • Author(s)
      Sato, T. (途中略),Koshiba, S., (途中略), Arai, Y.(合計15名、本研究者は13番目)
    • Journal Title

      Int. J. Cancer

      Volume: 145 Issue: 2 Pages: 484

    • DOI

      10.1002/ijc.32115

    • URL

      https://localhost/en/publications/cde7b33f-fab3-4eee-aea5-392f180a8863

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lactate dehydrogenase C is required for the protein expression of a sperm-specific isoform of lactate dehydrogenase A2018

    • Author(s)
      Dodo Mina、Kitamura Hiroshi、Shima Hiroki、Saigusa Daisuke、Wati Sisca Meida、Ota Nao、Katsuoka Fumiki、Chiba Hatsune、Okae Hiroaki、Arima Takahiro、Igarashi Kazuhiko、Koseki Takeyoshi、Sekine Hiroki、Motohashi Hozumi
    • Journal Title

      The Journal of Biochemistry

      Volume: 165 Issue: 4 Pages: 323

    • DOI

      10.1093/jb/mvy108

    • NAID

      40021893390

    • URL

      https://pure.teikyo.jp/en/publications/3ce041b9-b7fc-4f79-8894-395bc617553f

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional characterization of 50 CYP2D6 allelic variants by assessing primaquine 5-hydroxylation2018

    • Author(s)
      Saito Takahiro、Gutierrez Rico Evelyn Marie、Kikuchi Aoi、Kaneko Akira、Kumondai Masaki、Akai Fumika、Saigusa Daisuke、Oda Akifumi、Hirasawa Noriyasu、Hiratsuka Masahiro
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 33 Issue: 6 Pages: 250

    • DOI

      10.1016/j.dmpk.2018.08.004

    • URL

      https://localhost/en/publications/9cf01e18-f07a-42b5-b52b-f57a30ee11d1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Functional characterization of 40 CYP2B6 allelic variants by assessing efavirenz 8-hydroxylation2018

    • Author(s)
      Watanabe Takashi、Saito Takahiro、Rico Evelyn Marie Gutierrez、Hishinuma Eiji、Kumondai Masaki、Maekawa Masamitsu、Oda Akifumi、Saigusa Daisuke、Saito Sakae、Yasuda Jun、Nagasaki Masao、Minegishi Naoko、Yamamoto Masayuki、Yamaguchi Hiroaki、Mano Nariyasu、Hirasawa Noriyasu、Hiratsuka Masahiro
    • Journal Title

      Biochemical Pharmacology

      Volume: 156 Pages: 420-430

    • DOI

      10.1016/j.bcp.2018.09.010

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Metabolomic changes in the mouse retina after optic nerve injury.2018

    • Author(s)
      Sato K, Saigusa D, Saito R, Fujioka A, Nakagawa Y, Nishiguchi KM, Kokubun T, Motoike IN, Maruyama K, Omodaka K, Shiga Y, Uruno A, Koshiba S, Yamamoto M, Nakazawa T.
    • Journal Title

      Sci Rep

      Volume: 8 Issue: 1 Pages: 11930-11930

    • DOI

      10.1038/s41598-018-30464-z

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metabolomic Analysis of Mouse Brain after a Transient Middle Cerebral Artery Occlusion by Mass Spectrometry Imaging2018

    • Author(s)
      Abe T, Niizuma K, Kanoke A, Saigusa D, Saito R, Uruno A, Fujimura M, Yamamoto M, Tominaga T.
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 58 Issue: 9 Pages: 384-392

    • DOI

      10.2176/nmc.oa.2018-0054

    • NAID

      130007484209

    • ISSN
      0470-8105, 1349-8029
    • URL

      https://pure.teikyo.jp/en/publications/803c8578-3ab3-4996-bfa3-ad1c0e6cbe91

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intracellular S1P Levels Dictate Fate of Different Regions of the Hippocampus following Transient Global Cerebral Ischemia2018

    • Author(s)
      Rashad S, Niizuma K, Saigusa D, Han X, Sato-Maeda M, Saito R, Uruno A, Fujimura M, Ikawa S, Yamamoto M, Tominaga T.
    • Journal Title

      Neuroscience

      Volume: 384 Pages: 188

    • DOI

      10.1016/j.neuroscience.2018.05.015

    • URL

      https://localhost/en/publications/290db9a6-c31d-4376-92c9-3c95618fceb0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impact of the oral adsorbent AST-120 on organ-specific accumulation of uremic toxins: LC-MS/MS and MS imaging techniques2018

    • Author(s)
      Emiko Sato, Daisuke Saigusa, Eikan Mishima, Taeko Uchida, Daisuke Miura, Tomomi Morikawa-Ichinose, Kiyomi Kisu, Akiyo Sekimoto, Ritsumi Saito, Yuji Oe, Yotaro Matsumoto, Yoshihisa Tomioka, Takefumi Mori, Nobuyuki Takahashi, Hirosi Sato, Takaaki Abe, Toshimitsu Niwa, and Sadayosi Ito
    • Journal Title

      Toxins

      Volume: 10 Issue: 1 Pages: 19-33

    • DOI

      10.3390/toxins10010019

    • URL

      https://pure.teikyo.jp/en/publications/38415128-9d93-475a-999c-0ebe6631ad11

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Liver Zonation Index of Drug Transporter and Metabolizing Enzyme Protein Expressions in Mouse Liver Acinus<sup>s</sup>2018

    • Author(s)
      Tachikawa Masanori、Sumiyoshiya Yuna、Saigusa Daisuke、Sasaki Kazunari、Watanabe Michitoshi、Uchida Yasuo、Terasaki Tetsuya
    • Journal Title

      Drug Metab Dispos

      Volume: 46 Issue: 5 Pages: 610

    • DOI

      10.1124/dmd.117.079244

    • URL

      https://localhost/en/publications/5d09f9f1-d3d5-4dac-9645-842615725750

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Autotaxin–lysophosphatidic acid–LPA<sub>3</sub> signaling at the embryo-epithelial boundary controls decidualization pathways2017

    • Author(s)
      Aikawa Shizu、Kano Kuniyuki、Inoue Asuka、Wang Jiao、Saigusa Daisuke、Nagamatsu Takeshi、Hirota Yasushi、Fujii Tomoyuki、Tsuchiya Soken、Taketomi Yoshitaka、Sugimoto Yukihiko、Murakami Makoto、Arita Makoto、Kurano Makoto、Ikeda Hitoshi、Yatomi Yutaka、Chun Jerold、Aoki Junken
    • Journal Title

      EMBO J

      Volume: 36 Issue: 14 Pages: 2146

    • DOI

      10.15252/embj.201696290

    • URL

      https://pure.teikyo.jp/en/publications/9eff2a14-8b59-4329-98bc-70cc556391fc

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Evidence Suggests Sphingosine 1-Phosphate Might Be Actively Generated, Degraded, and Transported to Extracellular Spaces With Increased S1P <sub>2</sub> and S1P <sub>3</sub> Expression in Colon Cancer2017

    • Author(s)
      Uranbileg B, Nishikawa T, Ikeda H, Kurano M, Sato M, Saigusa D, Aoki J, Watanabe T, Yatomi Y.
    • Journal Title

      Clin Colorectal Cancer.

      Volume: 17 Issue: 2 Pages: 30369-9

    • DOI

      10.1016/j.clcc.2017.11.004

    • URL

      https://localhost/en/publications/d098fb62-2329-4603-ac82-13a91a0bc0b5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 疾患モデル動物のメタボローム組織分布解析による疾患発症リスク因子の同定2019

    • Author(s)
      三枝大輔、齋藤律水、宇留野晃
    • Organizer
      第92回日本内分泌学会学術総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 疾患モデルマウスにおける質量分析メタボローム解析が切り拓く新たな創薬の道筋2019

    • Author(s)
      三枝大輔、齋藤律水、宇留野晃
    • Organizer
      日本プロテオーム学会2019年大会・第70回日本電気泳動学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] MSイメージングによる疾患モデル動物解析と創薬への応用性について2019

    • Author(s)
      三枝大輔、齋藤律水、宇留野晃
    • Organizer
      第32回バイオメディカル分析科学シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Metabolic Profiling of Hepatocellular Carcinoma by High-Definition Mass Spectrometry2019

    • Author(s)
      Daisuke Saigusa
    • Organizer
      Tohoku Forum for Creativity Thematic Program 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Impact of the DIUTHAME for Distribution Analysis of Metabolites on Biological Tissues by DESI-MSI2019

    • Author(s)
      Daisuke Saigusa, Masahiro Kotani, Takayuki Ohmura
    • Organizer
      ASMS2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MALDI-MSI分析における導電性粘着フィルムの生体組織切片作成への有用性について2019

    • Author(s)
      三枝大輔、齋藤律水、川本孔明、宇留野晃、可野邦行、青木淳賢、山本雅之、川本忠文
    • Organizer
      第44回医用マススペクトル学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 質量分析計によるヒト肝がん浸潤バイオマーカー探索2019

    • Author(s)
      三枝大輔・永井滉士・Baasanjav Uranbileg・蔵野信・池田均・矢冨裕・富岡佳久・青木淳賢
    • Organizer
      第13回日本緩和医療薬学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 生体内脂質分子を高感度且つ網羅的に定量するためのノウハウ2018

    • Author(s)
      三枝大輔
    • Organizer
      第60回 日本脂質生化学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] High-Definition Mass Spectrometryによるヒト肝がん組織メタボローム解析2018

    • Author(s)
      三枝大輔
    • Organizer
      第5回 包括的緩和医療科学学術研究会、第6回 Tokyo 疼痛緩和次世代研究会合同研究会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Mass Spectrometry Imaging による生体内メタボローム組織分布解析2018

    • Author(s)
      三枝大輔
    • Organizer
      第40回生体膜と薬物の相互作用シンポジウム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Metabolic Profiling of Clinical and Cohort Studies for Searching Biomarkers2018

    • Author(s)
      D. Saigusa, I.N. Motoike, S. Koshiba
    • Organizer
      2018 Mass Spectrometry for Clinical Diagnosis
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] High-Definition Mass Spectrometryによるヒト肝がん組織のメタボローム解析2018

    • Author(s)
      三枝大輔・永井滉士・Baasanjav Uranbileg・蔵野信・長谷川潔・國土典宏・池田均・矢冨裕・富岡佳久・青木淳賢
    • Organizer
      日本質量分析学会・日本プロテオーム学会2018年合同大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Metabolic profiling of Hepatocellular Carcinoma by High-Definition Mass Spectrometry2018

    • Author(s)
      D.Saigusa, K. Nagai, B. Uranbileg, M. Kurano, H. Ikeda, Y. Yatomi, Y. Tomioka, J. Aoki
    • Organizer
      Metabolomics 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] High-Definition Mass Spectrometryによるヒト肝がん組織のメタボロミクス解析2018

    • Author(s)
      三枝大輔・永井滉士・Baasanjav Uranbileg・蔵野信・長谷川潔・國土典宏・池田均・矢冨裕・富岡佳久・青木淳賢
    • Organizer
      第43回医用マススペクトル学会年会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 標準化合物なしで正確な相対定量を行うための考え方2018

    • Author(s)
      三枝大輔
    • Organizer
      第160回 質量分析関西談話会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] MSイメージング技術のメタボローム解析への応用について2018

    • Author(s)
      三枝大輔
    • Organizer
      質量分析イメージングセミナー 2018
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 質量分析計を用いる大規模メタボローム解析におけるデータ補正について2017

    • Author(s)
      三枝大輔、元池育子、小柴生造
    • Organizer
      第65回質量分析総合討論会
    • Related Report
      2017 Research-status Report
  • [Presentation] Establishment of Normalization Protocol for Global Metabolomics in a Large-scale Study Using Mass Spectrometry2017

    • Author(s)
      D.Saigusa, I.N.Motoike, S.Koshiba
    • Organizer
      Metabolomics2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] DART-MS によるリアルタイムメタボロミクスの基盤技術開発2017

    • Author(s)
      三枝大輔
    • Organizer
      第42回日本医用マススペクトル学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] High-Definition Mass Spectrometryによるヒト肝がん組織メタボローム解析2017

    • Author(s)
      三枝大輔、永井滉士、Baasanjav Uranbileg、蔵野信、池田均、矢冨裕、富岡佳久、青木淳賢
    • Organizer
      第10回メタボロームシンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] 大規模コホートメタボロームリファレンスの薬物代謝解析への活用2017

    • Author(s)
      三枝大輔
    • Organizer
      日本薬物動態学会 第32回年会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Patent(Industrial Property Rights)] 組織切片上の分布に基づいたGSHの検出法および診断用データの採取方法2019

    • Inventor(s)
      国立大学法人東北大学
    • Industrial Property Rights Holder
      国立大学法人東北大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-122085
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] イオン化法及び質量分析法2019

    • Inventor(s)
      三枝大輔
    • Industrial Property Rights Holder
      三枝大輔
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-066619
    • Filing Date
      2019
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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