Pathological diagnosis by paraffin section proteotyping that opens up a new field of molecular pathology
| Project/Area Number |
21K19365
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 49:Pathology, infection/immunology, and related fields
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| Research Institution | Tohoku University |
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Principal Investigator |
Uchida Yasuo 東北大学, 薬学研究科, 准教授 (70583590)
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| Project Period (FY) |
2021-07-09 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | プロテオタイピング / パラフィン切片 / 病理診断 / 分子病理学 / レーザーマイクロダイセクション |
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| Outline of Research at the Start |
生体組織における病態分子機構の解明やバイオマーカー開発において、標的定量プロテオミクスが有用な技術であるという認識が定着しつつある。しかし、十分な例数の凍結組織を用いた研究は未だ難しい。また少数の標的タンパク質に限定した解析であることから、得られる情報量に限界であった。これを解決するためには、パラフィン組織を用いたタンパク質発現の網羅的定量法が必要であるが、従来法は再現性が極めて悪かった。本研究では、パラフィン組織を用いた高精度な「プロテオタイピング」によって、分子病理学の新領域を拓くことを目標とする。
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| Outline of Final Research Achievements |
The aim of this study was to realize a new pathological diagnosis called 'proteotyping' with high accuracy using paraffin tissue. We successfully developed a new method to quantitatively elucidate the pathological molecular mechanisms in the tissue regions or cells of interest in paraffin sections, by combining the laser microdissection, facilitated protein extraction and trypsin digestion by the PCT method, accurate and comprehensive mass spectrometry measurements by the SWATH method, and in silico peptide selection in data analysis. The application of this method to tissue sections of cerebral amyloid angiopathy has demonstrated that it is an effective method for exploring and elucidating novel molecular mechanisms in human brain diseases at the protein level.
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| Academic Significance and Societal Importance of the Research Achievements |
タンパク質の“定量”は診断などの様々な臨床的な目的に欠かせない手法である。しかし、日常的な病理診断に利用されているFFPE組織に対して有用な定量法は確立されておらず、挑戦的な課題とされてきた。本研究によって、FFPE検体で利用可能な、高精度かつ網羅的なタンパク質定量技術が開発された。細胞内分子ネットワークでのあらゆる分子・カスケードの活性化状態を定量的に評価する診断基盤が確立し、最も活性化している責任分子・カスケードの同定が可能になり、患者毎に最適化された治療が実現できる。
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Report
(3 results)
Research Products
(30 results)
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[Journal Article] A Human Blood-Arachnoid Barrier Atlas of Transporters, Receptors, Enzymes, Tight Junction and Marker Proteins: Comparison with Dog and Pig in Absolute Abundance2022
Author(s)
Uchida Y, Takeuchi H, Goto R, Braun C, Fuchs H, Ishiguro N, Takao M, Tano M, Terasaki T
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Journal Title
J Neurochem
Volume: -
Issue: 2
Pages: 187-208
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Regional Differences in the Absolute Abundance of Transporters, Receptors and Tight Junction Molecules at the Blood-Arachnoid Barrier and Blood-Spinal Cord Barrier among Cervical, Thoracic and Lumbar Spines in Dogs2022
Author(s)
Takeuchi H, Suzuki M, Goto R, Tezuka K, Fuchs H, Ishiguro N, Terasaki T, Braun C, Uchida Y
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Journal Title
Pharm Res
Volume: 39(7)
Issue: 7
Pages: 1393-1413
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Quantitative Targeted Absolute Proteomics for Better Characterization of an In Vitro Human Blood-Brain Barrier Model Derived from Hematopoietic Stem Cells2022
Author(s)
Dehouck MP, Tachikawa M, Hoshi Y, Omori K, Maurage CA, Strecker G, Dehouck L, Boucau MC, Uchida Y, Gosselet F, Terasaki T, Karamanos Y
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Journal Title
Cells
Volume: 11(24)
Issue: 24
Pages: 3963-3963
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] An Atlas of the Quantitative Protein Expression of Anti- Epileptic-Drug Transporters, Metabolizing Enzymes and Tight Junctions at the Blood-Brain Barrier in Epileptic Patients2021
Author(s)
Sato R, Ohmori K, Umetsu M, Takao M, Tano M, Grant G, Porter B, Bet A, Terasaki T, Uchida Y
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Journal Title
Pharmaceutics
Volume: 13(12)
Issue: 12
Pages: 2122-2122
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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