■ 1. tRNA modifications and diseases

It has been known that tRNAs are chemically modified in bacteria and yeast. In contrast, the human study had not been done because it was unknown that abnormal tRNA modification caused the development of diseases. We first identified that Cdkal1 was a tRNA modification enzyme, which catalyzed tRNALys. We generated pancreatic b cell-specific knockout mice and shoed the molecular mechanism on deficit of Cdkal1 function inhibited insulin secretion using the mice. Moreover, we recently novel tRNA modification enzyme in human and are demonstrating the physiological functions of these enzymes using each knockout mice and patient samples. We clarified that abnormal tRNA modifications are involved in the development of some diseases such as arrhythmia, mental retardation and mitochondrial diseases in addition to diabetes.

■ 2. Development of protein transduction therapy and the
application for the induction of differentiation of human
iPS cells to pancreatic b cells and anti-cancer therapy

We developed a protein transduction therapy using poly-arginine. We are capable of delivering and functioning proteins and peptide in cells using the method. We are now trying the induction of differentiation of human iPS cells to pancreatic b cells by protein transduction therapy. We succeeded to develop the method and to generate the cells efficiently and safety. Moreover, we are developing membrane-permeable anti-cancer peptides targeting to tumor in vivo using protein transduction therapy.