Project 1

Dissecting cancer biology with reprogramming technology

Epigenetic regulation plays a critical role in 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. We are interested in unveiling epigenetic regulation in the cellular differentiation, the maintenance of cellular identity, and the pathogenesis including cancer. Taking advantage of reprogramming technology, we have devised reprogrammable mouse models in which epigenetic regulation and eventually cell fate can be altered in vivo. By analysing in vivo reprogramming process, we aim to uncover the epigenetic regulation in cancer development, maintenance, and progression. Finally, we will try to develop a novel approach targeting epigenetic regulation to treat cancer patients.

Ito et al. Cell Reports 2022

 

Project 2

In vivo reprogramming for tissue regeneration and rejuvenation

We have devised in vivo reprogramming systems (Reprogrammable Mouse) in which iPS cells can be induced in living mice. Recent analyses of in vivo reprogramming process have revealed unappreciated mechanisms regarding senescence, tissue regeneration, and rejuvenation. By analyzing the response to cell fate perturbations at the organismal level, we aim to clarify the molecular basis of aging and tissue regeneration. Furthermore, we apply these reprogamming systems to develop innovative strategies for tissue regeneration and rejuvenation.

Ohnishi et al. Cell 2014　　　　　　　　　　　　　　 　Taguchi et al. Cell Stem Cell 2017

Project 3

Expansion of mature islet cells as a regenerative strategy targeting diabetes

We showed that a Mycl-mediated reprogramming expands functional islet cells. We aim to apply these methods to islet transplantation therapy through amplification of cadaveric islet cells in vitro. We also try to induce the proliferation of mature islet cells in vivo by gene therapy. The ultimate goal of our study is to develop regenerative medicine and to restore the function of aging pancreatic islets using reprogramming technology.

 

Hirano et al. Nature Metabolism 2022

 

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