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Potential pathogenesis and novel therapeutic targets by focusing on epigenomic regulation of small molecule metabolism in melanoma

Research Project

Project/Area Number 22K16262
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Fukumoto Takeshi  神戸大学, 医学研究科, 准教授 (80778770)

Project Period (FY) 2022-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2022: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords悪性黒色腫 / がん代謝 / メラノーマ代謝 / エクソーム解析 / メタボロミクス / バイオマーカー / マルチオミクス / トランスオミクス / メラノーマ / 低分子代謝 / グルタミン代謝 / エピゲノム制御
Outline of Research at the Start

ゲノム・低分子代謝物のマルチオミクス解析により、メラノーマ細胞におけるゲノム変異発現および代謝産物を網羅的に解析し、メラノーマに特徴的な「がん代謝」、特にグルタミン代謝に着目し、代謝リプログラミングとクロストークするエピゲノム制御に関与する遺伝子(遺伝子X)を特定する。さらに、メラノーマの『グルタミン代謝』制御を標的にした新たなメラノーマ治療を摸索し、新規治療戦略のバイオマーカー(コンパニオン診断薬)の特定を目指す。

Outline of Final Research Achievements

Two planned omics analyses have been completed to elucidate the low molecular metabolism in melanoma and to search for therapeutic seeds targeting specific metabolites using Japanese melanoma samples. We successfully collected comprehensive exome analysis data from formalin-fixed paraffin-embedded samples by using a next-generation sequencer and metabolomics data by using blood samples from the same individuals. Samples were selectively collected from melanoma and normal areas by using laser microdissection on slides prepared from formalin-fixed paraffin-embedded blocks. We have also collected data in the normal area, which was considered technically difficult.

Academic Significance and Societal Importance of the Research Achievements

人種間によりメラノーマの疾患感受性遺伝子やその変異のタイプが異なっている可能性が指摘されており、本研究で取り組む日本人のヒトメラノーマサンプルを用いたマルチオミクス解析は極めて重要である。本研究で得られた2つのオミクスデータから多階層にわたるマルチオミクス解析を行うことが出来たなら、日本人同一患者のサンプルからヒト個体内でダイナミックに形成されるゲノム・低分子代謝物の関係を見出すことができる。それにより、メラノーマにおける新規作用点を標的とした画期的な治療シーズ及びバイオマーカーの探索が進む。

Report

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

    (13 results)

All 2024 2023 2022 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Int'l Joint Research] University of Oregon(米国)

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Immune checkpoint inhibitors for metastatic uveal melanoma: a meta-analysis2024

    • Author(s)
      Yamada Kayoko、Takeuchi Masaki、Fukumoto Takeshi、Suzuki Minako、Kato Ai、Mizuki Yuki、Yamada Norihiro、Kaneko Takeshi、Mizuki Nobuhisa、Horita Nobuyuki
    • Journal Title

      Scientific Reports

      Volume: 14 Issue: 1 Pages: 7887-7887

    • DOI

      10.1038/s41598-024-55675-5

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA repair ability in a patient with voriconazole-related squamous cell carcinoma that required differential diagnosis from xeroderma pigmentosum2024

    • Author(s)
      Fukumoto Takeshi、Harada Tomoka、Ito Takamichi、Fukushima Satoshi、Ono Ryusuke、Furue Masutaka、Nishigori Chikako
    • Journal Title

      Journal of Dermatological Science

      Volume: - Issue: 2 Pages: 00028-8

    • DOI

      10.1016/j.jdermsci.2024.02.005

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemo-Senolytic Therapeutic Potential against Angiosarcoma2024

    • Author(s)
      Wang Xuebing、Yik-Lok Chung Claire、Yoshioka Ai、Hashimoto Shinya、Jimbo Haruki、Tanizawa Hideki、Ohta Shinya、Fukumoto Takeshi、Noma Ken-ichi
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 24 Issue: 10 Pages: 00268-9

    • DOI

      10.1016/j.jid.2024.03.026

    • Related Report
      2023 Annual Research Report
  • [Journal Article] CD4/CD8 double‐negative T‐cell lymphoma successfully treated with a combination of bexarotene and total skin electron beam therapy2023

    • Author(s)
      Tanigawa Ayano、Fukumoto Takeshi、Imamura Shinya、Nakamura Korefumi、Tanaka Tomonori、Itoh Tomoo、Nakano Eiji、Nishigori Chikako、Kubo Akiharu
    • Journal Title

      The Journal of Dermatology

      Volume: - Issue: 7

    • DOI

      10.1111/1346-8138.16739

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] The best dosage of nivolumab plus ipilimumab combination for melanoma brain metastases2022

    • Author(s)
      Fukumoto Takeshi、Horita Nobuyuki
    • Journal Title

      Translational Oncology

      Volume: 22 Pages: 101449-101449

    • DOI

      10.1016/j.tranon.2022.101449

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Severe and delayed-onset acneiform eruptions as an adverse reaction to regorafenib2022

    • Author(s)
      Otsuka Haruhiko、Fukumoto Takeshi、Kiyota Naomi、Takemori Chihiro、Jimbo Haruki、Nishigori Chikako
    • Journal Title

      Dermatology Reports

      Volume: 14 Issue: 2

    • DOI

      10.4081/dr.2022.9303

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Presentation] 老化メラノサイトでのホメオスタシスの変化2023

    • Author(s)
      福本毅
    • Organizer
      第5回 日本白斑学会学術大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Imatinibが奏功した KIT p.Asn655Lys変異を伴う粘膜悪性黒色腫の一例2023

    • Author(s)
      八木田 隼啓、新川 衣里子、福本 毅、藤原 進、大郷 真理子、柴田 慶子、久保 亮治、金原 史郎、南 博信
    • Organizer
      第39回日本皮膚悪性腫瘍学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 基底細胞癌を合併し診断に苦慮した脂腺腫の1例2023

    • Author(s)
      大幡万里恵、福本毅、後藤彩、新川衣里子、藤原進、吉岡愛育、神保直江、久保亮治
    • Organizer
      第39回日本皮膚悪性腫瘍学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 露光部に有棘細胞癌を多発し色素性乾皮症を疑われたボリコナゾール長期内服例2023

    • Author(s)
      後藤 彩、原田朋佳、福本 毅、小野竜輔、伊東孝通、福島聡、古江増隆、錦織千佳子、久保亮治
    • Organizer
      第122回日本皮膚科学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Seeds for new therapeutic strategies of malignant melanoma2023

    • Author(s)
      Takeshi Fukumoto Mizuho Fukunaga-Kalabis, Rajasekharan Somasundaram, Akiharu Kubo, Chikako Nishigori, Rugang Zhang, and Meenhard Herlyn
    • Organizer
      25th International Pigment Cell Conference
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The landscape of genetic alterations of UVB-induced skin tumors in DNA repair-deficient mice2022

    • Author(s)
      Ai Yoshioka, Hirofumi Nakaoka, Takeshi Fukumoto, Ituro Inoue, Chikako Nishigori, Akiharu Kubo, Makoto Kunisada
    • Organizer
      第47回日本研究皮膚科学会学術大会
    • Related Report
      2022 Research-status Report

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Published: 2022-04-19   Modified: 2025-01-30  

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