The University of Tokyo · Medicine
Professor Atsushi Iwama's research lab focuses on the molecular mechanisms governing hematopoietic stem cell (HSC) self-renewal, lineage commitment, and aging, with a particular emphasis on epigenetic regulators such as Polycomb group proteins (e.g., EZH2, BMI1) and TET2. The lab investigates how somatic mutations in epigenetic regulators contribute to the pathogenesis of myeloid malignancies, including myelodysplastic syndromes (MDS) and MDS/MPN overlap disorders. Using genetic models, patient-derived samples, and functional assays, the lab explores the interplay between epigenetic dysregulation and stem cell fate decisions in both normal hematopoiesis and leukemogenesis. The research also extends to tumor-initiating cells in hepatocellular carcinoma, highlighting the role of EZH2 in cancer stemness and therapeutic resistance.
Figures are computed from collected data and may differ slightly.
Polycomb group (PcG) proteins are essential regulators of hematopoietic stem cells. Recent extensive mutation analyses of the myeloid malignancies have revealed that inactivating somatic mutations in PcG genes such as EZH2 and ASXL1 occur frequently in patients with myelodysplastic disorders including myelodysplastic syndromes (MDSs) and MDS/myeloproliferative neoplasm (MPN) overlap disorders (MDS/MPN). In our patient cohort, EZH2 mutations were also found and often coincided with tet methylcyto
Recent advances in stem cell biology have identified tumor-initiating cells (TICs) in a variety of cancers including hepatocellular carcinoma (HCC). Polycomb group gene products such as BMI1 and EZH2 have been characterized as general self-renewal regulators in a wide range of normal stem cells and TICs. We previously reported that Ezh2 tightly regulates the self-renewal and differentiation of murine hepatic stem/progenitor cells. However, the role of EZH2 in tumor-initiating HCC cells remains u
Myeloid progenitor cells give rise to a variety of progenies including dendritic cells. However, the mechanism controlling the diversification of myeloid progenitors into each progeny is largely unknown. PU.1 and CCAAT/enhancing binding protein (C/EBP) family transcription factors have been characterized as key regulators for the development and function of the myeloid system. However, the roles of C/EBP transcription factors have not been fully identified because of functional redundancy among
Hematopoietic stem cells (HSCs) exhibit functional alterations, such as reduced regenerative capacity and myeloid-biased differentiation, with age. The HSC niche, which is essential for the maintenance of HSCs, also undergoes marked changes with aging. However, it has been technically challenging to directly evaluate the contribution of niche aging to age-associated HSC alterations without niche-damaging myeloablation in HSC transplantation assays. We herein transplanted an excess of aged HSCs i
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