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Discovery of high capacity transporters contributing to the drug transport at the human blood-brain barrier

Research Project

Project/Area Number 16H06218
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Medical pharmacy
Research InstitutionTohoku University

Principal Investigator

Uchida Yasuo  東北大学, 薬学研究科, 講師 (70583590)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥25,220,000 (Direct Cost: ¥19,400,000、Indirect Cost: ¥5,820,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Keywords血液脳関門 / 血液クモ膜関門 / トランスポーター・酵素・受容体探索 / 中枢薬物動態 / qGAP法 / SWATH法 / qTAP法 / プロテオミクス / 血液脊髄関門 / 血液脳脊髄液関門 / 網羅的基質探索 / トランスポーター探索 / SWATH
Outline of Final Research Achievements

The central nervous system (CNS) barriers including blood-brain barrier (BBB) is an important route to exchange a variety of substances including drugs between peripheral and CNS tissues. Transporting proteins expressed at the plasma membrane play important roles. The previous technologies and studies were not able to pursue the kinds, amounts and functions of transporting proteins at the plasma membrane, and mainly using rodents but not human materials. In the present study, we established comprehensive absolute quantitative proteomics “qGAP method” applicable for membrane proteins, and comprehensively elucidated new transport-molecular mechanisms in the CNS barriers including human BBB. The findings of many transporters (abundant expressions of OAT1, OAT3, MATE1, OCT2 etc) enabled to rationally understand the CNS pharmacokinetics. In conclusion, the present study was the first to systematically establish the basis of human CNS barrier biology.

Academic Significance and Societal Importance of the Research Achievements

ヒトを含めた大動物とげっ歯類の間では、血液脳関門の輸送機構に定量的な種差があることが先行研究から明らかになっていた。従来の中枢関門研究は、げっ歯類の使用を中心としたものであったため、ヒトの疾患治療を考えるうえで、大きな乖離があった。これに対して、本研究では、ヒト血液脳関門を含めた中枢関門における輸送分子機構を初めて体系的に解明した。特に、中枢組織の周りを覆うクモ膜が、末梢と中枢の間の重要な関門であり、多様な物質輸送機構を有することを明らかにしたことは、中枢領域のあらゆる研究に対して新しい潮流を生み出したといえる。本研究成果は、中枢疾患治療薬の開発戦略に大きく貢献することが期待される。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (97 results)

All 2020 2019 2018 2017 2016 Other

All Int'l Joint Research (13 results) Journal Article (29 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 24 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (52 results) (of which Int'l Joint Research: 9 results,  Invited: 16 results) Book (1 results) Remarks (2 results)

  • [Int'l Joint Research] スイス連邦工科大学(スイス)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Cochin Institute/パリ第五大学(フランス)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] ヘルシンキ大学/東フィンランド大学(フィンランド)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] スタンフォード大学(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Polish Academy of Sciences(ポーランド)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] スイス連邦工科大学(スイス)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Cochin Institute/パリ第五大学(フランス)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Cochin Institute/パリ第五大学(フランス)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] スイス連邦工科大学(スイス)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] ヘルシンキ大学/東フィンランド大学(フィンランド)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Cochin Institute/パリ第五大学(フランス)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] スイス連邦工科大学(スイス)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] ヘルシンキ大学/東フィンランド大学(フィンランド)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Abundant Expression of OCT2, MATE1, OAT1, OAT3, PEPT2, BCRP, MDR1, and xCT Transporters in Blood-Arachnoid Barrier of Pig and Polarized Localizations at CSF- and Blood-Facing Plasma Membranes.2020

    • Author(s)
      Uchida Y, Goto R, Takeuchi H, Luczak M, Usui T, Tachikawa M, Terasaki T.
    • Journal Title

      Drug Metab Dispos

      Volume: 48(2) Issue: 2 Pages: 135-145

    • DOI

      10.1124/dmd.119.089516

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Comparison of absolute protein abundances of transporters and receptors among blood-brain barriers at different cerebral regions and blood-spinal cord barrier in human and rat2020

    • Author(s)
      Y Uchida, Y Yagi, M Takao, M Tano, M Umetsu, S Hirano, T Usui, M Tachikawa, and T Terasaki
    • Journal Title

      Mol Pharm

      Volume: -

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 4つの中枢関門の分子機構の解明に基づくヒトの脳内薬物濃度の予測と中枢疾患の新たな創薬フィールドの開拓2020

    • Author(s)
      内田康雄
    • Journal Title

      薬事日報

      Volume: 12286

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Physiological and pharmacological roles of “Blood-Arachnoid Barrier”, a new interface of central nervous system: Importance of quantitative proteomics to open up a new world2020

    • Author(s)
      Y Uchida
    • Journal Title

      Proteome Letters

      Volume: 1

    • NAID

      130007891646

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selective Protein Expression Changes of Leukocyte-Migration-Associated Cluster of Differentiation Antigens at the Blood–Brain Barrier in a Lipopolysaccharide-Induced Systemic Inflammation Mouse Model without Alteration of Transporters, Receptors or Tight Junction-Related Protein2019

    • Author(s)
      Sato K, Tachikawa M, Watanabe M, Uchida Y, Terasaki T.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 6 Pages: 944-953

    • DOI

      10.1248/bpb.b18-00939

    • NAID

      130007657682

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-06-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amyloid beta(25-35) impairs docosahexaenoic acid efflux by down-regulating fatty acid transport protein 1 (FATP1/SLC27A1) protein expression in human brain capillary endothelial cells.2019

    • Author(s)
      Ochiai Y, Uchida Y, Tachikawa M, Couraud PO, Terasaki T.
    • Journal Title

      J Neurochem.

      Volume: 150(4) Issue: 4 Pages: 385-401

    • DOI

      10.1111/jnc.14722

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Toward a Consensus on Applying Quantitative Liquid Chromatography-Tandem Mass Spectrometry Proteomics in Translational Pharmacology Research: A White Paper.2019

    • Author(s)
      Prasad B, Achour B, Artursson P, Hop CECA, Lai Y, Smith PC, Barber J, Wisniewski JR, Spellman D, Uchida Y, Zientek MA, Unadkat JD, Rostami-Hodjegan A.
    • Journal Title

      Clin Pharmacol Ther.

      Volume: 106(3) Issue: 3 Pages: 525-543

    • DOI

      10.1002/cpt.1537

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Distinct roles of ezrin, radixin and moesin in maintaining the plasma membrane localizations and functions of human blood-brain barrier transporters2019

    • Author(s)
      Hoshi Yutaro、Uchida Yasuo、Kuroda Takashi、Tachikawa Masanori、Couraud Pierre-Olivier、Suzuki Takashi、Terasaki Tetsuya
    • Journal Title

      Journal of Cerebral Blood Flow & Metabolism

      Volume: - Issue: 7 Pages: 1533-1545

    • DOI

      10.1177/0271678x19868880

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Quantitative Protein Expression in the Human Retinal Pigment Epithelium: Comparison Between Apical and Basolateral Plasma Membranes With Emphasis on Transporters.2019

    • Author(s)
      Hellinen L, Sato K, Reinisalo M, Kidron H, Rilla K, Tachikawa M, Uchida Y, Terasaki T, Urtti A.
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 60(15) Issue: 15 Pages: 5022-5034

    • DOI

      10.1167/iovs.19-27328

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 中枢疾患時の血液脳関門P糖タンパク質の機能変動機構の解明と中枢関門創薬への新展開2019

    • Author(s)
      内田康雄、臼井拓也、寺崎哲也
    • Journal Title

      医学のあゆみ

      Volume: 271(1) Pages: 104-111

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Oxidative stress-induced activation of Abl and Src kinases rapidly induces P-glycoprotein internalization via phosphorylation of caveolin-1 on tyrosine-14, decreasing cortisol efflux at the blood-brain barrier2019

    • Author(s)
      Hoshi Y, Uchida Y, Tachikawa M, Ohtsuki S, Couraud PO, Suzuki T, Terasaki T
    • Journal Title

      J Cereb Blood Flow Metab

      Volume: - Issue: 2 Pages: 420-436

    • DOI

      10.1177/0271678x18822801

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Identification of blood-brain barrier-permeable proteins derived from peripheral organ: In vivo and in vitro evidence of blood-to-brain transport of creatine kinase2019

    • Author(s)
      Sato K, Tachikawa M, Watanabe M, Miyauchi E, Uchida Y, Terasaki T
    • Journal Title

      Mol Pharm

      Volume: - Issue: 1 Pages: 247-257

    • DOI

      10.1021/acs.molpharmaceut.8b00975

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cluster of Differentiation 46 is the Major Receptor in Human Blood-Brain Barrier Endothelial Cells for Uptake of Exosomes Derived from Brain-Metastatic Melanoma Cells (SK-Mel-28)2019

    • Author(s)
      Kuroda H, Tachikawa M, Yagi Y, Umetsu M, Nurdin A, Miyauchi E, Watanabe M, Uchida Y, Terasaki T.
    • Journal Title

      Mol. Pharm.

      Volume: 16 Issue: 1 Pages: 292-304

    • DOI

      10.1021/acs.molpharmaceut.8b00985

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of Claudin-11 in Disruption of Blood-Brain, -Spinal Cord, and -Arachnoid Barriers in Multiple Sclerosis2019

    • Author(s)
      Uchida Y, Sumiya T, Tachikawa M, Yamakawa T, Murata S, Yagi Y, Sato K, Stephan A, Ito K, Ohtsuki S, Couraud PO, Suzuki T, Terasaki T.
    • Journal Title

      Mol. Neurobiol,

      Volume: 56 Issue: 3 Pages: 2039-2056

    • DOI

      10.1007/s12035-018-1207-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 次世代型定量プロテオミクスに基づく中枢関門の新規密着結合分子の同定および多発性硬化症の中枢関門破綻への関与2019

    • Author(s)
      内田康雄
    • Journal Title

      ファルマシア

      Volume: 55 Pages: 320-324

    • NAID

      130007621940

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Uniprotデータベース2019

    • Author(s)
      内田康雄
    • Journal Title

      ファルマシア

      Volume: 55

    • NAID

      130007621935

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Evaluation of Organic Anion Transporter 1A2-knock-in Mice as a Model of Human Blood-brain Barrier2018

    • Author(s)
      Sano Y, Mizuno T, Mochizuki T, Uchida Y, Umetsu M, Terasaki T, Kusuhara H
    • Journal Title

      Drug Metab Dispos

      Volume: 46 Issue: 11 Pages: 1767-1775

    • DOI

      10.1124/dmd.118.081877

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SWATH-MS法って何?優れた定量精度・感度・網羅性を兼ね備えた次世代型定量プロテオミクス2018

    • Author(s)
      内田康雄
    • Journal Title

      薬剤学「最近のトピックス」

      Volume: 78 Pages: 228-234

    • NAID

      130007480620

    • Related Report
      2018 Annual Research Report
  • [Journal Article] High Expression of UGT1A1/1A6 in Monkey Small Intestine: Comparison of Protein Expression Levels of Cytochromes P450, UDP-Glucuronosyltransferases, and Transporters in Small Intestine of Cynomolgus Monkey and Human2018

    • Author(s)
      Akazawa T, Uchida Y, Miyauchi E, Tachikawa M, Ohtsuki S, Terasaki T
    • Journal Title

      Mol Pharm.

      Volume: 15 Issue: 1 Pages: 127-140

    • DOI

      10.1021/acs.molpharmaceut.7b00772

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ATP-binding cassette transporter A subfamily 8 is a sinusoidal efflux transporter for cholesterol and taurocholate in mouse and human liver2018

    • Author(s)
      Sasaki K, Tachikawa M, Uchida Y, Hirano S, Kadowaki F, Watanabe M, Ohtsuki S, Terasaki T
    • Journal Title

      Mol Pharm

      Volume: 15 Issue: 2 Pages: 343-355

    • DOI

      10.1021/acs.molpharmaceut.7b00679

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Drug clearance from cerebrospinal fluid mediated by organic anion transporters 1 (Slc22a6) and 3 (Slc22a8) at arachnoid membrane of rats.2018

    • Author(s)
      Zhang Z, Tachikawa M, Uchida Y, Terasaki T.
    • Journal Title

      Mol Pharm

      Volume: 15(3) Issue: 3 Pages: 911-922

    • DOI

      10.1021/acs.molpharmaceut.7b00852

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of blood biomarkers in glioblastoma by SWATH mass spectrometry and quantitative targeted absolute proteomics.2018

    • Author(s)
      Miyauchi E, Furuta T, Ohtsuki S, Tachikawa M, Uchida Y, Sabit H, Obuchi Wm Baba T, Watanabe M, Terasaki T, Nakada M
    • Journal Title

      PLoS One

      Volume: 13 Issue: 3 Pages: e0193799-e0193799

    • DOI

      10.1371/journal.pone.0193799

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The blood-brain barrier fatty acid transport protein 1 (FATP1/SLC27A1) supplies docosahexaenoic acid to the brain, and insulin facilitates transport2017

    • Author(s)
      Ochiai Y, Uchida Y, Ohtsuki S, Tachikawa M, Aizawa S, Terasaki T
    • Journal Title

      J Neurochem

      Volume: 141 Issue: 3 Pages: 400-412

    • DOI

      10.1111/jnc.13943

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Actin filament-associated protein 1 (AFAP-1) is a key mediator in inflammatory signaling-induced rapid attenuation of intrinsic P-gp function in human brain capillary endothelial cells.2017

    • Author(s)
      Yutaro Hoshi, Yasuo Uchida, Masanori Tachikawa, Sumio Ohtsuki, Tetsuya Terasaki
    • Journal Title

      Journal of Neurochemistry

      Volume: 印刷中 Issue: 2 Pages: 247-262

    • DOI

      10.1111/jnc.13960

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Inner Blood-Retinal Barrier Dominantly Expresses Breast Cancer Resistance Protein: Comparative Quantitative Targeted Absolute Proteomics Study of CNS Barriers in Pig2017

    • Author(s)
      Zhang Z, Uchida Y, Hirano S, Ando D, Kubo Y, Auriola S, Akanuma S, Hosoya K, Urtti A, Terasaki T, Tachikawa M
    • Journal Title

      Mol Pharm

      Volume: 14 Issue: 11 Pages: 3729

    • DOI

      10.1021/acs.molpharmaceut.7b00493

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Scrambled Internal Standard Method for High-Throughput Protein Quantification by Matrix-Assisted Laser Desorption Ionization Tandem Mass Spectrometry2017

    • Author(s)
      Yoneyama T, Ohtsuki S, Tachikawa M, Uchida Y, Terasaki T
    • Journal Title

      J Proteome Res

      Volume: 16 Issue: 4 Pages: 1556-1565

    • DOI

      10.1021/acs.jproteome.6b00941

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LC-MS/MS Based Quantitation of ABC and SLC Transporter Proteins in Plasma Membranes of Cultured Primary Human Retinal Pigment Epithelium Cells and Immortalized ARPE19 Cell Line2017

    • Author(s)
      Pelkonen L, Sato K, Reinisalo M, Kidron H, Tachikawa M, Watanabe M, Uchida Y, Urtti A, Terasaki T
    • Journal Title

      Mol Pharm

      Volume: 14 Issue: 3 Pages: 605-613

    • DOI

      10.1021/acs.molpharmaceut.6b00782

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Quantitative Atlas of Cytochrome P450, UDP-Glucuronosyltransferase, and Transporter Proteins in Jejunum of Morbidly Obese Subjects2016

    • Author(s)
      Miyauchi E, Tachikawa M, Decleves X, Uchida Y, Bouillot JL, Poitou C, Oppert JM, Mouly S, Bergmann JF, Terasaki T, Scherrmann JM, Lloret-Linares C
    • Journal Title

      Mol Pharm

      Volume: 13 Issue: 8 Pages: 2631-40

    • DOI

      10.1021/acs.molpharmaceut.6b00085

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Quantitative Targeted Absolute Proteomics of Transporters and Pharmacoproteomics-Based Reconstruction of P-Glycoprotein Function in Mouse Small Intestine2016

    • Author(s)
      Akazawa T, Uchida Y, Tachikawa M, Ohtsuki S, Terasaki T
    • Journal Title

      Mol Pharm

      Volume: 13 Issue: 7 Pages: 2443-56

    • DOI

      10.1021/acs.molpharmaceut.6b00196

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 定量プロテオミクスに基づく血液脳関門の輸送機能および病態変動機構の解明2020

    • Author(s)
      内田康雄(日本薬学会奨励賞受賞講演)
    • Organizer
      日本薬学会 第140年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 定量プロテオミクスを用いたヒト脈絡叢における膜タンパク質の網羅的発現解析2020

    • Author(s)
      臼井拓也、内田康雄、後藤諒平、三城智人、田野光敏、高尾昌樹、寺崎哲也
    • Organizer
      日本薬学会 第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] SWATH定量プロテオミクスに基づくヒト小児てんかんの焦点部位における血液脳関門と脳実質組織の病態変動機構の網羅的解明2020

    • Author(s)
      佐藤理沙、内田康雄、大森広太郎、梅津美奈、Gerald Grant、Brenda Porter、Anthony Bet、立川正憲、臼井拓也、寺崎哲也
    • Organizer
      日本薬学会 第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 定量プロテオミクスによるヒト血液クモ膜関門における薬物輸送担体及び薬物代謝酵素の発現量解析2020

    • Author(s)
      竹内妃奈、内田康雄、後藤諒平、臼井拓也、田野光敏、高尾昌樹、寺崎哲也
    • Organizer
      日本薬学会 第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Laser Microdissectionを用いたホルマリン固定パラフィン包埋切片の病変部位特異的なプロテオミクス定量系の確立:胆管結紮マウス肝臓のタンパク質発現量変動解析2020

    • Author(s)
      半田拓巳、内田康雄、佐々木颯、臼井拓也、寺崎哲也
    • Organizer
      日本薬学会 第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Key Issues and Our Solutions in Transporter Proteomics2019

    • Author(s)
      Y Uchida
    • Organizer
      The Seminar of University of Eastern Finland, School of Pharmacy
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Blood-brain barrier P-glycoprotein activation as a new potential therapy of brain infarct2019

    • Author(s)
      Y Uchida
    • Organizer
      34th JSSX annual conference
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Discovery of up- or down-regulated proteins in recurrent glioblastoma by SWATH-MS analysis2019

    • Author(s)
      S Kawarada, Y Uchida, S Tamai, M Nakada, T Terasaki
    • Organizer
      34th JSSX annual conference
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Next generation quantitative proteomics “SWATH-MS法”2019

    • Author(s)
      内田康雄
    • Organizer
      東京大学大学院薬学系研究科セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] (永井財団大学院学生スカラシップ採択)網羅的かつ高精度なトランスポーター基質探索に向けたカクテル輸送実験におけるSWATH一斉定量法の評価2019

    • Author(s)
      笠森なな、内田康雄、寺崎哲也
    • Organizer
      日本薬剤学会第34年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 網羅的定量プロテオミクスSWATH法を用いた神経膠芽腫における初発と再発腫瘍組織のタンパク質発現解析2019

    • Author(s)
      川原田翔平、内田康雄、玉井翔、中田光俊、寺崎哲也
    • Organizer
      日本薬剤学会第34年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] (口頭発表部門で優秀発表賞を受賞)脈絡叢と脳軟髄膜の標的プロテオミクス解析:ブタ1 頭あたりの脈絡叢と脳軟髄膜におけるトランスポータータンパク質の発現量解析と膜タンパク質の膜局在の網羅的解明2019

    • Author(s)
      後藤諒平、内田康雄、竹内妃奈、Magdalena Luczak、臼井拓也、立川正憲、寺崎哲也
    • Organizer
      第41回生体膜と薬物の相互作用シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 薬剤耐性型てんかん患者の血液脳関門で薬物代謝酵素が発現上昇する。2019

    • Author(s)
      佐藤理沙、内田康雄、大森広太郎、梅津美奈、Gerald Grant、Brenda Porter、Anthony Bet、立川正憲、臼井拓也、寺崎哲也
    • Organizer
      第58回日本薬学会東北支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ブタ血液クモ膜関門におけるトランスポーター13分子の局在一斉解明2019

    • Author(s)
      竹内妃奈、内田康雄、後藤諒平、Magdalena Luczak、臼井拓也、寺崎哲也
    • Organizer
      第58回日本薬学会東北支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Anti-epileptic drug metabolizing enzymes are upregulated at the blood-brain barrier in pharmacoresistant childhood epilepsy: SWATH-based comprehensive quantitative proteomic study2019

    • Author(s)
      R Sato, Y Uchida, K Omori, M Umetsu, G Grant, B Porter, A Bet, M Tachikawa, T Usui, and T Terasaki
    • Organizer
      34th JSSX annual conference
    • Related Report
      2019 Annual Research Report
  • [Presentation] (英語口頭発表部門で優秀口頭発表賞を受賞(47演題中4演題)学部4年生が受賞するのは快挙)OCT2 protein is expressed in CSF side of the porcine blood-arachnoid barrier, while MATE1 is in blood side: Application of qTAP to transporter localization2019

    • Author(s)
      H Takeuchi, Y Uchida, R Goto, M Luczak, T Usui and T Terasaki
    • Organizer
      34th JSSX annual conference
    • Related Report
      2019 Annual Research Report
  • [Presentation] 膜タンパク質に対する網羅的なタンパク質絶対定量法 “QGAP 法 ” の開発:ヒト血液脳関門における網羅的な絶対発現量アトラス2019

    • Author(s)
      平野誠巳, 内田康雄, 梅津美奈, 後藤諒平, 八木悠太, 立川正憲, 田野光敏, 高尾昌樹, 寺崎哲也
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 定量プロテオミクスによるヒト血液脊髄関門における膜タンパク質の定量的発現プロファイルの解明2019

    • Author(s)
      八木悠太, 内田康雄, 梅津美奈, 平野誠巳, 立川正憲, 田野光敏, 高尾昌樹, 寺崎哲也
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Membrane Enrichment and Sample Preparation for Targeted Proteomics2018

    • Author(s)
      Uchida Y
    • Organizer
      ISSX Workshop on LC-MS proteomics
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Usefulness of Pressure Cycling Technology-assisted sample process for accurate and comprehensive quantitative proteomics using FFPE section; application for ADME-related proteins2018

    • Author(s)
      H Sasaki, Y Uchida, M Tachikawa, T Terasaki
    • Organizer
      第33回日本薬物動態学会・MDO国際合同年会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification and absolute quantification of Transporters in the isolated human brain microvessels by next-generation quantitative proteomics SWATH-MS2018

    • Author(s)
      M Umetsu, Y Uchida, S Hirano, M Takao, M Tachikawa, T Terasaki
    • Organizer
      第33回日本薬物動態学会・MDO国際合同年会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of a novel tight junction protein “Claudin-11” at the four barriers of central nervous system and its involvement for the barrier breakdown in Multiple Sclerosis2018

    • Author(s)
      Y Uchida, T Sumiya, M Tachikawa, T Yamakawa, S Murata, Y Yagi, K Sato, A Stephan, K Ito, S Ohtsuki, PO Couraud, T Suzuki, and T Terasaki
    • Organizer
      第33回日本薬物動態学会・MDO国際合同年会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Next generation quantitative proteomics “SWATH-MS法”2018

    • Author(s)
      内田康雄
    • Organizer
      Mass Spectrometry and Proteomics 2018 (MSP2018)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] SWATH-MSプロテオミクスによる網羅的かつ高精度なバイオマーカー探索と定量2018

    • Author(s)
      内田康雄
    • Organizer
      第45回BMSコンファレンス(BMS2018)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 次世代型定量プロテオミクスに基づく中枢疾患創薬のための薬物中枢移行性の制御機構の解明と中枢移行性予測2018

    • Author(s)
      内田康雄
    • Organizer
      武田薬品工業株式会社湘南研究所セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 次世代型定量プロテオミクスSWATH法に基づく多発性硬化症の中枢関門の破綻メカニズムの解明2018

    • Author(s)
      内田康雄
    • Organizer
      第40回生体膜と薬物の相互作用シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 多発性硬化症における中枢関門の破綻への新規密着結合分子claudin-11の寄与の解明2018

    • Author(s)
      内田康雄、住谷智仁, 立川正憲, 山川達也, 村田将, 八木悠太, 佐藤和貴, 伊藤克彰, 大槻純男, Pierre-Olivier Couraud, 鈴木貴, 寺崎哲也
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Pressure Cycling Techologyを用いたホルマリン固定パラフィン包埋切片プロテオミクス定量系の確立2018

    • Author(s)
      佐々木颯、内田康雄、立川正憲、寺崎哲也
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Pressure Cycling Technologyを用いたホルマリン固定パラフィン包埋切片プロテオミクス定量系の薬物関連タンパク質への応用2018

    • Author(s)
      佐々木颯, 内田康雄, 立川正憲, 寺崎哲也
    • Organizer
      第40回 生体膜と薬物の相互作用シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] ラット血液脊髄関門と血液脳関門におけるトランスポータータンパク質発現量の類似性と相違性の解明2018

    • Author(s)
      八木悠太、内田康雄、立川正憲、寺崎 哲也
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 細胞膜分画、SWATH及び高精度ペプチド選択を組み合わせた膜タンパク質のApical/Basolateral膜局在と絶対発現量の網羅的推定法の開発2018

    • Author(s)
      平野誠巳、内田康雄、立川正憲、後藤諒平、寺崎哲也
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ブタ脈絡叢と脳軟髄膜の網羅的・標的プロテオミクス解析:OATP1A2、OCT2及びMATE1の発現局在とCSF中薬物動態における役割2018

    • Author(s)
      後藤諒平、内田康雄、立川正憲、平野誠巳、張正宇、寺崎哲也
    • Organizer
      日本薬学会第138年会(優秀発表賞受賞)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 血液脳関門P糖タンパクのin vivo輸送機能の病態変動に“寄与”する分子機構の解明戦略: 酸化ストレス病態におけるAbl・Src kinasesの寄与2017

    • Author(s)
      内田康雄、星裕太朗、立川正憲、大槻純男、 寺崎哲也
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 網羅的定量プロテオミクスSWATH法を用いた血液脳関門透過型肝可溶性タンパク質の探索と輸送機構解明2017

    • Author(s)
      佐藤和貴、立川正憲、渡部通寿、 内田康雄、寺崎哲也
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 脳転移性メラノーマ細胞由来exosomesによるヒト脳毛細血管内皮細胞株hCMEC/D3のエネルギー代謝抑制制御2017

    • Author(s)
      陳瓊芳、内田康雄、黒田広樹、梅津美奈、八木悠太、立川正憲、寺崎哲也
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 網羅的定量プロテオミクスSWATH法および定量的標的プロテオミクスを用いた一次性膠芽腫の血漿診断タンパク質候補の同定2017

    • Author(s)
      宮内 英輔、立川 正憲、米山 敏広、内田 康雄、古田 拓也、中田 光俊、大槻 純男、寺崎 哲也
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Discovery proteomics of blood-brain barrier permeable endogenous protein candidates2017

    • Author(s)
      Yasuo Uchida, Kazuki Sato, Masanori Tachikawa, Tetsuya Terasaki
    • Organizer
      International Symposium on Drug Delivery and Pharmaceutical Sciences: Beyond the History (ISDDPS)
    • Place of Presentation
      京都
    • Year and Date
      2017-03-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] LC-MS/MS-based research for Blood-Brain Barrier and Malignant Brain Tumor2017

    • Author(s)
      Uchida Y
    • Organizer
      Seminar in Institute for Research in Biomedicine, University of Barcelona
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Investigation of the regulatory mechanism of blood-brain barrier P-glycoprotein transport function toward brain stroke/infarct therapy2017

    • Author(s)
      Uchida Y, Hoshi Y, Tachikawa M, Ohtsuki S, Terasaki T
    • Organizer
      BioMedical Transporters 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 海外留学へのすすめ:2年間のスイス留学2017

    • Author(s)
      内田康雄
    • Organizer
      東北大学薬学同窓会講演会 第1回グローバル薬学人講座
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 血液脳関門のP糖タンパク質の輸送機能の制御メカニズム2017

    • Author(s)
      内田康雄
    • Organizer
      第12回トランスポーター研究会年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ブタBRB, BBB及びBCSFBの輸送担体の絶対発現量解析:BCRPの重要性2017

    • Author(s)
      張正宇、内田康雄、平野誠巳、安藤大介、久保義行、 Seppo Auriola、赤沼伸乙、立川正憲、細谷健一、Arto Urtti、寺崎哲也
    • Organizer
      日本薬剤学会第32年会(最優秀発表賞受賞)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脳虚血性疾患の治療に向けた血液脳関門P-gp輸送機能の制御機構の解明2017

    • Author(s)
      内田康雄、星裕太朗、立川正憲、大槻純男、寺崎哲也
    • Organizer
      日本薬剤学会第32年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development of label free comprehensive absolute quantification method by SWATH-MS combined with in silico peptide selection criteria ~Its application for the hepatic drug delivery~2017

    • Author(s)
      平野誠巳、内田康雄、立川正憲、後藤諒平、寺崎哲也
    • Organizer
      日本薬物動態学会第32回年会(優秀口頭発表賞受賞)
    • Related Report
      2017 Annual Research Report
  • [Presentation] OUTER blood-CSF barrier (arachnoid membrane) abundantly expresses OAT1, OAT3, PEPT2 and BCRP proteins as compared to INNER blood-CSF barrier (choroid plexus)2017

    • Author(s)
      後藤諒平、内田康雄、立川正憲、平野誠巳、張正宇、寺崎哲也
    • Organizer
      日本薬物動態学会第32回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Proteomics based characterization of the blood-spinal cord barrier transporters in rats: Comparison with the blood-brain barrier2017

    • Author(s)
      八木悠太、立川正憲、内田康雄、寺崎哲也
    • Organizer
      日本薬物動態学会第32回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Blood-brain barrier P-glycoprotein activation strategy as a new therapy of brain infarct2017

    • Author(s)
      内田康雄、星裕太朗、立川正憲、大槻純男、寺崎哲也
    • Organizer
      日本薬物動態学会第32回年会(優秀口頭発表賞受賞)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 次世代型プロテオミクスSWATH法を用いた肝臓のトランスポーター群のタンパク質絶対発現量と局在の網羅的解析2017

    • Author(s)
      平野誠巳、内田 康雄、立川 正憲、後藤諒平、寺崎 哲也
    • Organizer
      第12回トランスポーター研究会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Quantitative phosphoproteomics for the regulatory mechanism of blood-brain barrier P-glycoprotein: Oxidative stress-induced activation of Abl and Src kinases enhanced P-glycoprotein internalization2016

    • Author(s)
      Hoshi Y, Uchida Y, Tachikawa M, Ohtsuki S, Terasaki T
    • Organizer
      11th GPEN (The Globalization of Pharmaceutics Education Network)
    • Place of Presentation
      Lawrence, Kansas, USA
    • Year and Date
      2016-11-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] リン酸化プロテオミクスに基づくAbl 及びSrc kinases によるP-glycoprotein の内在化制御機構の解明2016

    • Author(s)
      星 裕太朗、内田 康雄、立川 正憲、大槻 純男、寺崎 哲也
    • Organizer
      第11回トランスポーター研究会年会
    • Place of Presentation
      京都
    • Year and Date
      2016-07-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] P-gp絶対発現量、単分子輸送活性および蛋白質非結合型分率の統合によるP-gp基質の脳移行性の再構築とその脳移行性の種差の要因分析2016

    • Author(s)
      内田康雄
    • Organizer
      日本薬物動態学会 第10回ショートコース
    • Place of Presentation
      大阪
    • Year and Date
      2016-05-12
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Next generation quantitative proteomics “SWATH 法” の基礎と応用2016

    • Author(s)
      内田康雄
    • Organizer
      第12 回 東北大学学際科学フロンティア研究所FRIS セミナー
    • Place of Presentation
      仙台
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Book] Blood-arachnoid barrier as a dynamic physiological and pharmacological interface between cerebrospinal fluid and blood2020

    • Author(s)
      Y Uchida, R Goto, T Usui, M Tachikawa and T Terasaki
    • Publisher
      Springer
    • Related Report
      2019 Annual Research Report
  • [Remarks] 研究室ホームページ(内田康雄)

    • URL

      http://www.pharm.tohoku.ac.jp/~soutatsu/dds/profile/uchida.htm

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
  • [Remarks] 研究業績

    • URL

      http://www.pharm.tohoku.ac.jp/~soutatsu/dds/profile/uchida.htm

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2021-02-19  

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