The University of Tokyo · Medicine
Professor Ryuichi Okamoto's research lab focuses on intestinal epithelial biology, with a central emphasis on the molecular mechanisms governing intestinal stem cell plasticity, cell fate decisions, and tissue regeneration in health and disease. The lab investigates key signaling pathways such as Notch and transcription factors like ATOH1 in regulating epithelial homeostasis, repair, and tumorigenesis. Using advanced lineage-tracing and organoid-based models, the lab explores the regenerative potential of intestinal cells, particularly in the context of inflammatory bowel disease and mucosal healing. Their work also extends to ion channel function in intestinal epithelial physiology, particularly bestrophin-family calcium-activated chloride channels.
Figures are computed from collected data and may differ slightly.
Notch signaling regulates cell differentiation and proliferation, contributing to the maintenance of diverse tissues including the intestinal epithelia. However, its role in tissue regeneration is less understood. Here, we show that Notch signaling is activated in a greater number of intestinal epithelial cells in the inflamed mucosa of colitis. Inhibition of Notch activation in vivo using a gamma-secretase inhibitor resulted in a severe exacerbation of the colitis attributable to the loss of th
ATOH1 is a master transcription factor for the secretory lineage differentiation of intestinal epithelial cells (IECs). However, the comprehensive contribution of ATOH1<sup>+</sup> secretory lineage IECs to the homeostasis, repair, and tumorigenesis of the intestinal epithelium remains uncertain. Through our ATOH1<sup>+</sup> cell-lineage tracing, we show here that a definite number of ATOH1<sup>+</sup> IECs retain stem cell properties and can form ATOH1<sup>+</sup>IEC-derived clonal ribbons (AT
Inflammatory bowel disease (IBD) consists of two major idiopathic gastrointestinal diseases: ulcerative colitis and Crohn's disease. Although a significant advance has been achieved in the treatment of IBD, there remains a particular population of patients that are refractory to the conventional treatments, including the biologic agents. Studies have revealed the importance of "mucosal healing" in improving the prognosis of those difficult-to-treat patients, which indicates the proper and comple
Intestinal epithelial cells (IECs) regulate the absorption and secretion of anions, such as HCO3(-) or Cl(-). Bestrophin genes represent a newly identified group of calcium-activated Cl(-) channels (CaCCs). Studies have suggested that, among the four human bestrophin-family genes, bestrophin-2 (BEST2) and bestrophin-4 (BEST4) might be expressed within the intestinal tissue. Consistently, a study showed that BEST2 is expressed by human colonic goblet cells. However, their precise expression patte
Our analysis of adult acute lymphoblastic leukemia cases led to the identification of new potential target lesions relevant for the pathogenesis of acute lymphoblastic leukemia. However, no unequivocal pattern of submicroscopic genomic alterations was found to separate adult acute lymphoblastic leukemia from pediatric acute lymphoblastic leukemia. Therefore, apart from different therapy regimen, differences of prognosis between adult and pediatric acute lymphoblastic leukemia are probably based
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