Oda, Mayumi

写真a

Affiliation

School of Medicine, Department of Biochemistry (Shinanomachi)

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)

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Research Areas 【 Display / hide 】

  • Life Science / Veterinary medical science

  • Life Science / Genome biology

  • Life Science / Cardiology

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Research Themes 【 Display / hide 】

  • Epigenomics, 

    2006.01
    -
    Present

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    エピジェネティクス修飾とゲノム情報の関わりを中心に、発生・分化および疾患を考えていきたいと考えています。

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Papers 【 Display / hide 】

  • An organoid library unveils subtype-specific IGF-1 dependency via a YAP–AP1 axis in human small cell lung cancer

    Fukushima T., Togasaki K., Hamamoto J., Emoto K., Ebisudani T., Mitsuishi A., Sugihara K., Shinozaki T., Okada M., Saito A., Takaoka H., Ito F., Shigematsu L., Ohta Y., Takahashi S., Matano M., Kurebayashi Y., Ohgino K., Sato T., Kawada I., Asakura K., Hishida T., Asamura H., Ikemura S., Terai H., Soejima K., Oda M., Fujii M., Fukunaga K., Yasuda H., Sato T.

    Nature Cancer  2025

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    Small cell lung cancer (SCLC) is a devastating disease with limited therapeutic advancements. Although SCLC has recently been classified into four molecular subtypes, subtype-specific therapies are still lacking. Here, we established 40 patient-derived SCLC organoid lines with predominant TP53 and RB1 alterations and rare targetable genetic lesions. Transcriptome profiling divided the SCLC organoids into neuroendocrine (NE)-type SCLC and non-NE-type SCLC, with the latter characterized by YAP1 or POU2F3 expression. NE-type SCLC organoids grew independent of alveolar niche factors, whereas non-NE-type SCLC organoids relied on insulin-like growth factor (IGF)-1-driven YAP1 and AP1 activation. Therapeutic targeting of IGF-1, YAP1 and AP1 effectively suppressed the growth of non-NE-type organoids. Co-knockout of TP53 and RB1 in human alveolar cells altered their lineage toward the airway epithelium-like fate and conferred IGF-1 dependency, validating the subtype-phenotype connection. Our SCLC organoid library represents a valuable resource for developing biology-based therapies and has the potential to reshape the drug discovery landscape.

  • Generation of human adult hepatocyte organoids with metabolic functions

    Igarashi R., Oda M., Okada R., Yano T., Takahashi S., Pastuhov S., Matano M., Masuda N., Togasaki K., Ohta Y., Sato S., Hishiki T., Suematsu M., Itoh M., Fujii M., Sato T.

    Nature  2025

    ISSN  00280836

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    Proliferating hepatocytes often undergo ductal metaplasia to balance the energy trade-off between cellular functions and replication, hindering the expansion of human adult hepatocytes with functional competency1. Here we demonstrate that the combined activation of Wnt and STAT3 signalling enables long-term self-renewal of human adult hepatocyte organoids. YAP activation facilitates hepatocyte proliferation but commits it towards the biliary duct lineage. By contrast, STAT3 activation by oncostatin M induces hepatocyte proliferation while counteracting ductal metaplasia and maintaining the hepatic identity. Xenotransplanted hepatocyte organoids repopulate the recipient mouse liver and reconstitute the metabolic zonation structure. Upon niche factor removal and hormone supplementation, hepatocyte organoids form cord-like structures with bile canalicular networks and exhibit major liver metabolic functions comparable to those of in vivo hepatocytes. Hepatocyte organoids are amenable to gene editing, prompting functional modelling of inherent metabolic liver diseases. The new culture system offers a promising avenue for developing therapeutic strategies against human liver diseases.

  • Genotype-phenotype mapping of a patient-derived lung cancer organoid biobank identifies NKX2-1-defined Wnt dependency in lung adenocarcinoma

    Ebisudani T., Hamamoto J., Togasaki K., Mitsuishi A., Sugihara K., Shinozaki T., Fukushima T., Kawasaki K., Seino T., Oda M., Hanyu H., Toshimitsu K., Emoto K., Hayashi Y., Asakura K., Johnson T.A., Terai H., Ikemura S., Kawada I., Ishii M., Hishida T., Asamura H., Soejima K., Nakagawa H., Fujii M., Fukunaga K., Yasuda H., Sato T.

    Cell Reports 42 ( 3 )  2023.03

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    Human lung cancer is a constellation of tumors with various histological and molecular properties. To build a preclinical platform that covers this broad disease spectrum, we obtained lung cancer specimens from multiple sources, including sputum and circulating tumor cells, and generated a living biobank consisting of 43 lines of patient-derived lung cancer organoids. The organoids recapitulated the histological and molecular hallmarks of the original tumors. Phenotypic screening of niche factor dependency revealed that EGFR mutations in lung adenocarcinoma are associated with the independence from Wnt ligands. Gene engineering of alveolar organoids reveals that constitutive activation of EGFR-RAS signaling provides Wnt independence. Loss of the alveolar identity gene NKX2-1 confers Wnt dependency, regardless of EGFR signal mutation. Sensitivity to Wnt-targeting therapy can be stratified by the expression status of NKX2-1. Our results highlight the potential of phenotype-driven organoid screening and engineering for the fabrication of therapeutic strategies to combat cancer.

  • Identification of Quiescent LGR5<sup>+</sup> Stem Cells in the Human Colon

    Ishikawa K., Sugimoto S., Oda M., Fujii M., Takahashi S., Ohta Y., Takano A., Ishimaru K., Matano M., Yoshida K., Hanyu H., Toshimitsu K., Sawada K., Shimokawa M., Saito M., Kawasaki K., Ishii R., Taniguchi K., Imamura T., Kanai T., Sato T.

    Gastroenterology 163 ( 5 ) 1391 - 1406.e24 2022.11

    ISSN  00165085

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    Background & Aims: In the mouse intestinal epithelium, Lgr5+ stem cells are vulnerable to injury, owing to their predominantly cycling nature, and their progenies de-differentiate to replenish the stem cell pool. However, how human colonic stem cells behave in homeostasis and during regeneration remains unknown. Methods: Transcriptional heterogeneity among colonic epithelial cells was analyzed by means of single-cell RNA sequencing analysis of human and mouse colonic epithelial cells. To trace the fate of human colonic stem or differentiated cells, we generated LGR5-tdTomato, LGR5-iCasase9-tdTomato, LGR5-split-Cre, and KRT20-ERCreER knock-in human colon organoids via genome engineering. p27+ dormant cells were further visualized with the p27-mVenus reporter. To analyze the dynamics of human colonic stem cells in vivo, we orthotopically xenotransplanted fluorescence-labeled human colon organoids into immune-deficient mice. The cell cycle dynamics in xenograft cells were evaluated using 5-ethynyl-2′-deoxyuridine pulse-chase analysis. The clonogenic capacity of slow-cycling human stem cells or differentiated cells was analyzed in the context of homeostasis, LGR5 ablation, and 5-fluorouracil–induced mucosal injury. Results: Single-cell RNA sequencing analysis illuminated the presence of nondividing LGR5+ stem cells in the human colon. Visualization and lineage tracing of slow-cycling LGR5+p27+ cells and orthotopic xenotransplantation validated their homeostatic lineage-forming capability in vivo, which was augmented by 5-FU–induced mucosal damage. Transforming growth factor–β signaling regulated the quiescent state of LGR5+ cells. Despite the plasticity of differentiated KRT20+ cells, they did not display clonal growth after 5-FU–induced injury, suggesting that occupation of the niche environment by LGR5+p27+ cells prevented neighboring differentiated cells from de-differentiating. Conclusions: Our results highlight the quiescent nature of human LGR5+ colonic stem cells and their contribution to post-injury regeneration.

  • Intestinal epithelial organoids: regeneration and maintenance of the intestinal epithelium

    Oda M., Hatano Y., Sato T.

    Current Opinion in Genetics and Development 76 2022.10

    ISSN  0959437X

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    Vital functions of the intestines: digestion, absorption, and surface barrier are performed by the intestinal epithelium, which consists of various differentiated cells and intestinal stem cells. Recent technological advances in sequencing technology, including single-cell transcriptomics and epigenetic analysis, have facilitated the genetic characterization of diverse intestinal epithelial cell types and surrounding mesenchymal niche environments. Organoids have allowed biological analysis of the human intestinal epithelium in coordination with genome engineering, genetic lineage tracing, and transplantation into orthotopic tissue. Together, these technologies have prompted the development of organoid-based regenerative therapies for intestinal diseases, including short-bowel syndrome. This article provides an overview of the current understanding of intestinal epithelial self-renewal during homeostasis and regeneration and provides a perspective for future organoid medicine.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • Elucidation of molecular mechanisms underlying the flexibility of the comprehensive maintenance system of mature cell functions.

    2023.04
    -
    2027.03

    基盤研究(C), Principal investigator

  • Mechanism for cardiomyocyte-specific nuclear architecture and disease development by dynamic DNA demethylation system.

    2018.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

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Courses Taught 【 Display / hide 】

  • BIOCHEMISTRY

    2025

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Memberships in Academic Societies 【 Display / hide 】

  • The Japanese Society for Epigenetics

    　

  • The Molecular Biology Society of Japan

    　
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