Graduate School of Medicine  Doctorial Course in Medicine  Bioregulatory Medicine  Department of Biochemistry and Metabolic Science

Research Interests 【 display / non-display

  • Epigenetics

  • Adipocytes

  • Metabolism

  • Next generation sequencing

  • Histone modifications

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Graduating School 【 display / non-display


    Tohoku University     Graduated

Graduate School 【 display / non-display


    Tohoku University  Graduate School, Division of Natural Science  Department of Chemistry  Doctor's Course  Completed


    Tohoku University  Graduate School, Division of Natural Science  Department of Chemistry  Master's Course  Completed

Studying abroad experiences 【 display / non-display

  • 2008.01

    Oregon Health Science University   Postdoctoral researcher

Campus Career 【 display / non-display

  • 2023.11

    Akita University   Graduate School of Medicine   Doctorial Course in Medicine   Bioregulatory Medicine   Department of Biochemistry and Metabolic Science   Professor  

External Career 【 display / non-display

  • 2022.04

    Tohoku University   Graduate School of Medicine   Associate Professor  

  • 2017.04

    The University of Tokyo   Research Center for Advanced Science and Technology, Division of Metabolic Medicine   Associate Professor  

  • 2012.04

    The University of Tokyo   Research Center for Advanced Science and Technology, Division of Metabolic Medicine   Research Associate  

  • 2011.04

    The University of Tokyo   Research Center for Advanced Science and Technology, Division of Metabolic Medicine   Appointed Research Associate  

  • 2004.06

    Akita University   Faculty of Medicine   Postdoctoral Researcher  

Research Areas 【 display / non-display

  • Life Science / System genome science  / Epigenetics, Next generation sequencing

  • Life Science / Molecular biology  / Histone modifications, RNA modifications

  • Life Science / Metabolism and endocrinology  / Metabolism, Adipocytes

  • Life Science / Cell biology


Research Achievements 【 display / non-display

    ◆Original paper【 display / non-display

  • Environmental factor reversibly determines cellular identity through opposing Integrators that unify epigenetic and transcriptional pathways.

    Hiroki Takahashi, Ryo Ito, Yoshihiro Matsumura, Juro Sakai

    BioEssays : news and reviews in molecular, cellular and developmental biology ( BioEssays )  46 ( 2 ) e2300084   2023.11  [Refereed]

    Research paper (journal)   Domestic Co-author

    Organisms must adapt to environmental stresses to ensure their survival and prosperity. Different types of stresses, including thermal, mechanical, and hypoxic stresses, can alter the cellular state that accompanies changes in gene expression but not the cellular identity determined by a chromatin state that remains stable throughout life. Some tissues, such as adipose tissue, demonstrate remarkable plasticity and adaptability in response to environmental cues, enabling reversible cellular identity changes; however, the mechanisms underlying these changes are not well understood. We hypothesized that positive and/or negative "Integrators" sense environmental cues and coordinate the epigenetic and transcriptional pathways required for changes in cellular identity. Adverse environmental factors such as pollution disrupt the coordinated control contributing to disease development. Further research based on this hypothesis will reveal how organisms adapt to fluctuating environmental conditions, such as temperature, extracellular matrix stiffness, oxygen, cytokines, and hormonal cues by changing their cellular identities.

    DOI PubMed

  • Hypoxia activates SREBP2 through Golgi disassembly in bone marrow-derived monocytes for enhanced tumor growth.

    Ryuichi Nakahara, Sho Aki, Maki Sugaya, Haruka Hirose, Miki Kato, Keisuke Maeda, Daichi M Sakamoto, Yasuhiro Kojima, Miyuki Nishida, Ritsuko Ando, Masashi Muramatsu, Melvin Pan, Rika Tsuchida, Yoshihiro Matsumura, Hideyuki Yanai, Hiroshi Takano, Ryoji Yao, Shinsuke Sando, Masabumi Shibuya, Juro Sakai, Tatsuhiko Kodama, Hiroyasu Kidoya, Teppei Shimamura, Tsuyoshi Osawa

    The EMBO journal     e114032   2023.10  [Refereed]

    Research paper (journal)   Domestic Co-author

    Bone marrow-derived cells (BMDCs) infiltrate hypoxic tumors at a pre-angiogenic state and differentiate into mature macrophages, thereby inducing pro-tumorigenic immunity. A critical factor regulating this differentiation is activation of SREBP2-a well-known transcription factor participating in tumorigenesis progression-through unknown cellular mechanisms. Here, we show that hypoxia-induced Golgi disassembly and Golgi-ER fusion in monocytic myeloid cells result in nuclear translocation and activation of SREBP2 in a SCAP-independent manner. Notably, hypoxia-induced SREBP2 activation was only observed in an immature lineage of bone marrow-derived cells. Single-cell RNA-seq analysis revealed that SREBP2-mediated cholesterol biosynthesis was upregulated in HSCs and monocytes but not in macrophages in the hypoxic bone marrow niche. Moreover, inhibition of cholesterol biosynthesis impaired tumor growth through suppression of pro-tumorigenic immunity and angiogenesis. Thus, our findings indicate that Golgi-ER fusion regulates SREBP2-mediated metabolic alteration in lineage-specific BMDCs under hypoxia for tumor progression.

    DOI PubMed

  • Epitranscriptomics in metabolic disease.

    Yoshihiro Matsumura, Fan-Yan Wei, Juro Sakai

    Nature Metabolism ( Nature Metabolism )  5 ( 3 ) 370 - 384   2023.03  [Refereed]

    Research paper (journal)   Domestic Co-author

    While epigenetic modifications of DNA and histones play main roles in gene transcription regulation, recently discovered post-transcriptional RNA modifications, known as epitranscriptomic modifications, have been found to have a profound impact on gene expression by regulating RNA stability, localization and decoding efficiency. Importantly, genetic variations or environmental perturbations of epitranscriptome modifiers (that is, writers, erasers and readers) are associated with obesity and metabolic diseases, such as type 2 diabetes. The epitranscriptome is closely coupled to epigenetic signalling, adding complexity to our understanding of gene expression in both health and disease. Moreover, the epitranscriptome in the parental generation can affect organismal phenotypes in the next generation. In this Review, we discuss the relationship between epitranscriptomic modifications and metabolic diseases, their relationship with the epigenome and possible therapeutic strategies.

    DOI PubMed

  • Phosphoethanolamine Accumulation Protects Cancer Cells under Glutamine Starvation through Downregulation of PCYT2.

    Osawa T, Shimamura T, Saito K, Hasegawa Y, Ishii N, Nishida M, Ando R, Kondo A, Anwar M, Tsuchida R, Hino S, Sakamoto A, Igarashi K, Saitoh K, Kato K, Endo K, Yamano S, Kanki Y, Matsumura Y, Minami T, Tanaka T, Anai M, Wada Y, Wanibuchi H, Hayashi M, Hamada A, Yoshida M, Yachida S, Nakao M, Sakai J, Aburatani H, Shibuya M, Hanada K, Miyano S, Soga T, Kodama T

    Cell Reports   29 ( 1 ) 89 - 103.e7   2019.10  [Refereed]

    Research paper (journal)   Domestic Co-author

    Tolerance to severe tumor microenvironments, including hypoxia and nutrient starvation, is a common feature of aggressive cancer cells and can be targeted. However, metabolic alterations that support cancer cells upon nutrient starvation are not well understood. Here, by comprehensive metabolome analyses, we show that glutamine deprivation leads to phosphoethanolamine (PEtn) accumulation in cancer cells via the downregulation of PEtn cytidylyltransferase (PCYT2), a rate-limiting enzyme of phosphatidylethanolamine biosynthesis. PEtn accumulation correlated with tumor growth under nutrient starvation. PCYT2 suppression was partially mediated by downregulation of the transcription factor ELF3. Furthermore, PCYT2 overexpression reduced PEtn levels and tumor growth. In addition, PEtn accumulation and PCYT2 downregulation in human breast tumors correlated with poor prognosis. Thus, we show that glutamine deprivation leads to tumor progression by regulating PE biosynthesis via the ELF3-PCYT2 axis. Furthermore, manipulating glutamine-responsive genes could be a therapeutic approach to limit cancer progression.

    DOI PubMed

  • Downregulation of ERG and FLI1 expression in endothelial cells triggers endothelial-to-mesenchymal transition.

    Nagai N, Ohguchi H, Nakaki R, Matsumura Y, Kanki Y, Sakai J, Aburatani H, Minami T

    PLoS Genetics   14 ( 11 ) e1007826   2018.11  [Refereed]

    Research paper (journal)   Domestic Co-author

    DOI PubMed

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    ◆Other【 display / non-display

  • Multi-omics in lifestyle-related diseases

    松村欣宏, 高橋宙大, 伊藤亮, 米代武司, 米代武司, 稲垣毅, 稲垣毅, 酒井寿郎, 酒井寿郎

    実験医学   41 ( 15 )   2023


  • Metabolic syndrome and Epigenome

      49 ( 2 ) 56 - 62   2017.02

Grant-in-Aid for Scientific Research 【 display / non-display

  • Elucidation of epigenome dynamics that determines adipocyte differentiation

    Grant-in-Aid for Scientific Research(C)

    Project Year: 2022.04  -  2025.03 

  • Grant-in-Aid for Scientific Research(A)

    Project Year: 2021.04  -  2024.03 

  • Elucidation of epigenetic mechanisms that memorize inter-tissue communication

    Grant-in-Aid for Scientific Research(C)

    Project Year: 2019.04  -  2022.03  Investigator(s): Matsumura Yoshihiro

  • Elucidation of lifestyle-related diseases development due to environmental factors and epigenetic memory

    Grant-in-Aid for Scientific Research(S)

    Project Year: 2016.05  -  2021.03  Investigator(s): SAKAI Juro

  • Epigenetic mechanism of adipocyte dysfunction under overnutrition

    Grant-in-Aid for Scientific Research(C)

    Project Year: 2016.04  -  2019.03  Investigator(s): Matsumura Yoshihiro, Kawamura Takeshi

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