Masatoshi Hagiwara, M.D., Ph.D. Professor
Alternative splicing of pre-mRNA generates a highly dynamic human proteome through networks of coordinated splicing events, and is regulated on tissue-specific stage-dependent way. Our goal is to establish a new paradigm on the mechanism of morphogenesis from the view point of mRNA processing regulation. We will also try to find chemical modifiers of mRNA processing, which will be applicable for clinical therapy against malignant tumors, virus infections and neuromuscular diseases caused by aberrant splicing. We welcome enthusiastic young researchers who will challenge to open new fields of biology.
Research and Education1) Decipherment of splicing code
Alternative splicing events are dynamically regulated in developmental stage-dependent and tissue specific manners, and regulated by ‘splicing code’ made up of loosely defined consensus sequences. To decipher the splicing code, we have developed transgenic alternative splicing reporter systems that enable us to visualize alternative splicing events in living cells.
2) Development of new drugs to cure RNA diseases
There is a growing awareness that misregulations of mRNA processing are causative of many human diseases. We focused on the mRNA splicing process, and have developed compounds that alter the alternative splicing events or even reverse some misregulated splicing events.
3) Chemical biology
We are one of pioneers of chemical biology field, Chemical biology is one of new and rapidly growing research fields, and we are one of pioneer groups of this field. Using new techniques of chemical biology, we are challenging to develop novel drugs to cure hereditary diseases, cancers, virus infections, and other incurable diseases.
Recent Publications1.Yoshida M, Kataoka N, Miyauchi K, Ohe K, Iida K, Yoshida S, Nojima T, Okuno Y, Onogi H, Usui T, Takauchi A, Hosoya T, Suzuki T, and Hagiwara M, (2015) Rectifier of aberrant mRNA splicing recovers tRNA modification in familial dysautonomia. Proc Natl Acad Sci USA. 112(9):2764-2769.
2.Kuwasako K, Takahashi M, Unzai S, Tsuda K, Yoshikawa S, He F, Kobayashi N, Güntert P, Shirouzu M, Ito T, Tanaka A, Yokoyama S, Hagiwara M, Kuroyanagi H, and Muto Y. (2014) RBFOX and SUP-12 sandwich a guanine base to form a stable complex and regulate tissue-specific splicing. Struct. Mol. Biol. 21(9):778-786.
3.Yamamoto M, Onogi H, Kii I, Yoshida S, Iida K, Sakai H, Abe M, Tsubota T, Ito N, Hosoya T, and Hagiwara M. (2014) CDK9 inhibitor FIT-039 prevents replication of multiple DNA viruses. J Clin Invest. 124(8):3479–3488.
4.Pozo N, Zahonero C, Fernández P, Liñares JM, Ayuso A, Hagiwara M, Pérez A, Ricoy JR, Hernández-Laín A, Sepúlveda JM, Sánchez-Gómez P. (2013) Inhibition of DYRK1A destabilizes EGFR and reduces EGFR-dependent glioblastoma growth. J Clin Invest. 123(6):2475-2487.
5.Kuroyanagi H, Watanabe Y, and Hagiwara M. (2013) CELF family RNA-binding protein UNC-75 regulates two sets of mutually exclusive exons of the unc-32 gene in neuron-specific manners in Caenorhabditis elegans. PLoS Genet. 9(2):e1003337
Anatomy and Developmental BiologyProfessor: Masatoshi Hagiwara
Associate Professor: Akihide Takeuchi
Research Associate Professor: Minako Hoshi
Assistant Professor: Ryo Kimura, Akiko Kobayashi
Research Assistant Professor: Masayasu Toyomoto