Dept. of Clinical Application
Akitsu Hotta (Associate Professor)
Akitsu Hotta Ph.D.
By steering induced pluripotent stem (iPS) cells to differentiate into cells of various lineages capable of physiological function within the body, it may one day be possible to develop revolutionary cell-based medical treatments that overcome the problems of immune rejection and donor shortages. However, a number of hurdles remain to be cleared, such as the development of reliable methods for selecting high-quality iPS cells and the elimination of the risks of teratoma formation or the inadvertent inclusion of undifferentiated cells, before clinical applications can be achieved.
In my previous work, I used viral vector transgene delivery systems and epigenetic regulation of transcription to drive the undifferentiated pluripotent stem cell-specific expression of GFP and drug-resistance genes as a high-efficiency method of selecting human iPS cells. Through this work, I have engaged in the search for novel reprogramming factors as well as research into the derivation of various patient-specific iPS cell lines and the intra-nuclear changes that accompany the reprogramming process. Taking advantage of my experience in these areas, I will seek to develop techniques for the generation and selection of safer human iPS cells and novel iPS-based gene therapy approaches to the treatment of hemophilia and other genetic conditions.
More than half of all orphan diseases -- rare conditions with unclear onset mechanism and no effective treatment -- are thought to involve genetic abnormalities. In research and new therapy development for these diseases, effective genome modification technologies and a supply of patient-derived iPS cells can serve as powerful tools.
Among the technologies developed by the Hotta laboratory, whose main target disease is muscular dystrophy, are genome editing tools for genetic mutation repair using CRISPR and other systems, immune rejection prevention techniques based on modifying HLA-related genes in iPS cells, and gene delivery systems using viruses and compounds. Through organic combination of such new technologies, we are exploring the close but still unknown world of the genome with the aim of developing unique new technologies to support innovative therapies for muscular dystrophy and other orphan diseases caused by genetic mutation.