Although an accurate and complete genome sequence of various organisms have been made available, the function of genes, the epigenetic mechanisms that control gene expressions, the role of genomic elements, including non-coding elements, are not fully understood, especially at the organismal level. We establish in vivo experimental platforms using cutting-edge and genome-editing technologies in mice. The goal of our laboratory is to uncover various aspects of biology as well as pathogenesis of diseases using such advanced mouse models. Our effort should promote the interdisciplinary research that connects a wide range of research fields, including stem cell biology, immunology, and cancer biology, which eventually contributes to the development of novel strategy to control the detrimental effects of diseases and aging in humans.

Epigenetic regulation plays a critical role for the cellular differentiation, the stable maintenance of cellular identity, and the reprogramming process. Accumulating evidence suggests that epigenetic abnormalities represented by abnormal DNA methylation have been involved in various diseases as well. We are interested in unveiling epigenetic regulation in the cellular differentiation, the maintenance of cellular identity, and the pathogenesis including cancer. Particularly, taking advantage of reprogramming technology to actively alter epigenetic regulation, we are investigating the role of epigenetic regulation on cancer development, maintenance, and progression. Finally, we will try to develop a novel approach targeting epigenetic regulation to treat cancer patients.

Stem cells play an important role in homeostasis of organ function in multicellular organisms. They are responsible for tissue regeneration and their functional impairment upon aging causes various diseases in mammals. However, considering the complexity of multicellular organisms, it remains unclear how tissue microenvironment affects stem cell functions. We aim to elucidate the molecular basis for stem cell behavior in response to altered tissue microenvironments. The effort should eventually unveil the fundamental basis of how stem cells affect organismal functions in vivo and uncover the underlying mechanisms of tissue regeneration, various diseases and organismal aging. These findings may contribute to developing a feasible strategy to control the detrimental effects of stem cell dysfunction in diseases and aging.

Pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, have been derived and maintained in vitro under culture conditions that include stimulators and inhibitors of extrinsic signaling. Recent advances in stem cell cultivation have opened the possibility of capturing naive pluripotency, which is reminiscent of the pluripotency of inner cell mass cells, in vitro. Pluripotent stem cells offer a powerful experimental platform to understand the early mammalian development. Moreover, the disease modeling with pluripotent stem cells recaptures the development of various diseases in vitro. However, emerging evidence has revealed complexity of epigenetic regulation in pluripotent stem cells in vitro that reflects the developmental stage, gender, and species. We aim to understand epigenetic regulation of pluripotent stem cells and its impact on the developmental potential of pluripotent stem cells in rodents and humans.

 

 

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