The University of Tokyo · Medicine
Professor Mineo Kurokawa's research lab focuses on the molecular mechanisms underlying hematopoietic stem cell regulation and leukemogenesis, with a particular emphasis on transcriptional regulation, epigenetic modifications, and signal transduction in hematopoietic malignancies. The lab investigates how oncogenic fusion proteins such as AML1/Evi-1 disrupt tumor suppressor pathways like TGF-β signaling, and explores the non-canonical, DNA methylation-independent functions of leukemia-associated mutations such as DNMT3A R882H in stem cell self-renewal and differentiation block. Key research directions include the post-translational regulation of transcription factors like AML1 (RUNX1), their interactions with co-regulators such as mSin3A, and the epigenetic and signaling networks that drive leukemic transformation.
Figures are computed from collected data and may differ slightly.
The t(3;21)(q26;q22) chromosomal translocation associated with blastic crisis of chronic myelogenous leukemia results in the formation of the AML1/Evi-1 chimeric protein, which is thought to play a causative role in leukemic transformation of hematopoietic cells. Here we show that AML1/Evi-1 represses growth-inhibitory signaling by transforming growth factor-beta (TGF-beta) in 32Dcl3 myeloid cells. The activity of AML1/Evi-1 to repress TGF-beta signaling depends on the two separate regions of th
Despite the clinical impact of DNMT3A mutation on acute myeloid leukaemia, the molecular mechanisms regarding how this mutation causes leukaemogenesis in vivo are largely unknown. Here we show that, in murine transplantation experiments, recipients transplanted with DNMT3A mutant-transduced cells exhibit aberrant haematopoietic stem cell (HSC) accumulation. Differentiation-associated genes are downregulated without accompanying changes in methylation status of their promoter-associated CpG islan
The AML1 (RUNX1) gene, one of the most frequent targets of translocations associated with human leukemias, encodes a DNA-binding protein that plays pivotal roles in myeloid differentiation through transcriptional regulation of various genes. Previously, we reported that AML1 is phosphorylated on two serine residues with dependence on activation of extracellular signal-regulated kinase, which positively regulates the transcriptional activity of AML1. Here, we demonstrate that the interaction betw
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