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Spatial-temporal dynamics of genetic remodelling of the skin

Research Project

Project/Area Number 21K16210
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53050:Dermatology-related
Research InstitutionKyoto University

Principal Investigator

Ishida Yoshihiro  京都大学, 医学研究科, 助教 (70890622)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords乾癬 / アトピー性皮膚炎 / 皮膚がん / 紫外線 / 加齢 / 遺伝子変異 / クローン進化 / がん / 皮膚 / 老化 / 発がん
Outline of Research at the Start

皮膚ケラチノサイトのクローン拡大の全容はいまだ明らかでない。ヒト皮膚サンプルの体細胞変異の解析を行い、皮膚における遺伝的再構築の全体像を明らかにする。また、慢性疾患や環境暴露の程度の異なるサンプルを解析し、環境因子や加齢が表皮の遺伝的再構築に与える影響を解明する。正常組織と皮膚がんの変異プロファイルを比較し、正常組織から発がんに至る軌跡を明らかにする。それらの知見をもとに、多細胞生物における加齢、発がんの理解を深めることを目的とする。

Outline of Final Research Achievements

We investigated how chronic skin inflammatory diseases such as psoriasis and atopic dermatitis affect the accumulation of mutations in the skin. The results showed that psoriasis is associated with an increase in the acquisition of driver mutations from a young age. On the other hand, few driver mutations were found in atopic dermatitis, suggesting that cells with driver mutations may be eliminated in this condition. While neither psoriasis nor atopic dermatitis itself generates mutations, many of the mutations are caused by ultraviolet light exposure.

Academic Significance and Societal Importance of the Research Achievements

本研究は、乾癬やアトピー性皮膚炎などの慢性皮膚疾患が遺伝子変異やクローン拡大にどのように影響するかを解明した。その結果、乾癬では皮膚がんリスクを高める遺伝子変異が多く見つかり、アトピー性皮膚炎では変異が抑えられることが分かった。これにより、乾癬の早期治療が皮膚がん予防に有効である可能性が示唆された。また、皮膚疾患の治療法や予防策の開発に役立つ新たな知見が提供された。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (11 results)

All 2024 2023 2022

All Journal Article (10 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 10 results,  Open Access: 3 results) Presentation (1 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Emergence of multiple revertant keratinocyte clones in a patient with <scp>KID</scp> syndrome2024

    • Author(s)
      Ishida Y、Murata T、Kakiuchi N、Ogawa S、Kabashima K
    • Journal Title

      Journal of the European Academy of Dermatology and Venereology

      Volume: 38 Issue: 3

    • DOI

      10.1111/jdv.19595

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of the pentose phosphate pathway in macrophages is crucial for granuloma formation in sarcoidosis2023

    • Author(s)
      Nakamizo Satoshi、Sugiura Yuki、Ishida Yoshihiro、Ueki Yoko、Yonekura Satoru、Tanizaki Hideaki、Date Hiroshi、Yoshizawa Akihiko、Murata Teruasa、Minatoya Kenji、Katagiri Mikako、Nomura Seitaro、Komuro Issei、Ogawa Seishi、Nakajima Saeko、Kambe Naotomo、Egawa Gyohei、Kabashima Kenji
    • Journal Title

      Journal of Clinical Investigation

      Volume: 133 Issue: 23 Pages: 171088-171088

    • DOI

      10.1172/jci171088

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular Characterization of Aged Human Eccrine Sweat Gland Cells Using Single-Cell Transcriptomic Analysis2023

    • Author(s)
      Tie D, Ishida Y, Nakajima S, Kabashima K.
    • Journal Title

      The Journal of Investigative Dermatology

      Volume: 23 Issue: 6 Pages: 1389-1391.e5

    • DOI

      10.1016/j.jid.2023.11.013

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CYP4F22 p.V215D is a novel variant causative for lamellar ichthyosis.2023

    • Author(s)
      Ishida Yoshihiro、Saeki Kazuko、Ueda Marina、Lee‐Okada Hyeon‐Cheol、Doi Hiromi、Kambe Naotomo、Nakajima Saeko、Yokomizo Takehiko、Kabashima Kenji
    • Journal Title

      Journal of the European Academy of Dermatology and Venereology

      Volume: - Issue: 6

    • DOI

      10.1111/jdv.19680

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cutaneous Adnexal Adenocarcinoma: Genomic Analysis and Successful HER2-targeted Therapy of Metastatic Disease2023

    • Author(s)
      Hirano-Lotman Yui、Ishida Yoshihiro、Endo Yuichiro、Ogawa Seishi、Kabashima Kenji
    • Journal Title

      Acta Dermato-Venereologica

      Volume: 103 Pages: adv9399-adv9399

    • DOI

      10.2340/actadv.v103.9399

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of vasculogenic mesenchymal tumor in the mediastinum: whole-exome sequencing reveals origin from pre-existing germ cell tumor2023

    • Author(s)
      Fujii Hirotake、Yamada Yosuke、Yamamura Kentaro、Ishida Yoshihiro、Tsujimura Marina、Matsumoto Kazuhisa、Tanaka Satona、Date Hiroshi、Nishikawa Tadaaki、Yoshida Yukihiro、Kashima Jumpei、Yatabe Yasushi、Ogawa Seishi、Marx Alexander、Ulbright Thomas M.、Haga Hironori
    • Journal Title

      Virchows Archiv

      Volume: 未定 Issue: 5 Pages: 923-927

    • DOI

      10.1007/s00428-023-03529-2

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cronkhite-Canada Syndrome Mimicking COVID-19-related Symptoms2022

    • Author(s)
      Miyawaki Kayo、Komori Takaya、Ishida Yoshihiro、Sakaguchi Yuri、Honjo Hajime、Kudo Masatoshi、Otsuka Atsushi
    • Journal Title

      Acta Dermato-Venereologica

      Volume: 102 Pages: adv00812-adv00812

    • DOI

      10.2340/actadv.v102.3402

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Treatment With Topical Sirolimus for Recurrent Lymphatic Malformation of the External Urethral Meatus2022

    • Author(s)
      Yonekura Satoru、Komori Takaya、Ishida Yoshihiro、Kogame Toshiaki、Kabashima Kenji
    • Journal Title

      JAMA Dermatology

      Volume: 158 Issue: 11 Pages: 1331-1331

    • DOI

      10.1001/jamadermatol.2022.2793

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Filaggrin-deficient rats generated using zinc-finger nucleases spontaneously exhibit dry scaly skin2022

    • Author(s)
      Nakashima Chisa、Doi Hiromi、Nakajima Saeko、Mashimo Tomoji、Oga Toru、Ishida-Yamamoto Akemi、Honda Tetsuya、Ishida Yoshihiro、Otsuka Atsushi、Kabashima Kenji
    • Journal Title

      Allergology International

      Volume: 71 Issue: 4 Pages: 545-547

    • DOI

      10.1016/j.alit.2022.04.001

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Circadian rhythm affects the magnitude of contact hypersensitivity response in mice2022

    • Author(s)
      Miyake Toshiya、Egawa Gyohei、Chow Zachary、Asahina Ryota、Otsuka Masayuki、Nakajima Saeko、Nomura Takashi、Shibuya Rintaro、Ishida Yoshihiro、Nakamizo Satoshi、Murata Teruasa、Kitoh Akihiko、Kabashima Kenji
    • Journal Title

      Allergy

      Volume: 77 Issue: 9 Pages: 2748-2759

    • DOI

      10.1111/all.15314

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Clonal expansion of skin keratinocyte resolved at single-clone level2022

    • Author(s)
      Yoshihiro Ishida
    • Organizer
      European Society for Dermatological Research
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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