Research projects

Induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine and in vitro modeling of human diseases. To overcome their abnormal differentiation and tumorigenicity, the method to evaluate bona fide “appropriately reprogrammed human iPSCs” has been expected. In this study, by focusing on the differences of the tumorigeniticy (glioma-like tumor formation) among human iPSC clones caused by the incomplete reprogramming and genomic instability, we identified reprogramming recalcitrant genes as “Score card”, and examined their applicability to the evaluation of human iPSCs.

Cochlea dysplasia and the associated feature, cochlear nerve dysplasia have been difficult to provide clinical treatment, while the cause of the diseases is largely unknown. We conducted whole exome analysis of the families associated with these symptoms by Next Generation Sequencer and identified 2 novel candidate responsible genes. A candidate gene X appeared to be expressed in cochlear nerve, and was suggested to associate with neurite extension in our immunohistochemical and in vitro studies. The other candidate gene Y has already been shown to have significant role in inner ear development in mouse model, and was finally suggested to cause cochlea dysplasia in human in this study. Our results expanded our understanding of molecular pathology of cochlea and cochlear nerve dysplasia and will lead to development of better diagnosis and treatment.

Auditory Neuropathy (AN) is a new concept of hearing loss with the clinical feature of poor recognition of words. The purpose of this study is to reveal novel genetic causes of AN. By Sanger sequencing analysis in 36 patients with AN, we detected 11 novel OTOF mutations in 25 patients and 1 known GJB2 mutation in a patient. By whole genome SNP analysis followed by real time PCR analysis in 4 patients with monoallelic OTOF mutations, we did not detect large deletions in OTOF. With exome analysis in 10 patients who had not been found genetic causes by previous genetic analyses, we detected 3 candidates of novel AN genes (PNPLA3, RYR3, TACC2) and a novel OPA1 mutation which is likely to be a de novo mutation.