Members
Ajiro, Masahiko
（May 1, 2016 ～ March 31, 2023）
My research is focused on screening and characterization of splice-regulating small molecule compounds for disease-causing splicing mutations. RNA splicing is one of fundamental steps in the eukaryotic gene expression system, and its aberrant regulation is estimated to account for 30-35% of causal mutations in genetic diseases. Although splicing mutations disrupting essential nucleotides (e.g. GT/AG at splice donor/acceptor sites) cannot be managed, a subset of disease-associated missplicing can be interrupted by targeting splicing auxiliary factor(s) that selectively acts on disease-causing splicing. In order to evaluate activity of small molecule compounds for specific target splicing mutations, we apply SPREADD reporter system (Figure), a dual-colored fluorescent splicing reporter invented by Dr. Hagiwara in Kyoto University (Yoshida M et al. PNAS 112(9):2764-9), in combination with original focused-library for splice-regulating compounds. We currently apply this strategy for various types of splicing mutations, including pseudo exon creation by deep-intronic mutations. Through this approach, I aim to identify novel small molecule compounds and their functional mechanisms for responsive missplicing diseases toward a practical application.
Research Career
2016, May-present
Assistant professor, Dept. of Drug Discovery Medicine, Kyoto University Graduate School of Medicine, Japan
2013, Jan-2016, Apr.
Visiting Fellow, Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute, NIH, USA.
2010, May-2012, Dec.
Visiting Fellow, HIV and AIDS Malignancy Branch, National Cancer Institute, NIH, Bethesda, USA.
2007, Apr.-2010, Mar.
Ph.D. The University of Tokyo, Institute of Medical Science, Japan.
2005, Apr.-2007, Mar.
M.Sc. Tohoku University, Institute of Development, Aging and Cancer, Japan.
2001, Apr.-2005, Mar.
B.Sc. Tohoku University, Dept. of Applied Chemistry, Chemical Engineering and Biomolecular Engineering, Japan.
Publications
Publication list（Link to NCBI PubMed）
Contact
Address: Bldg. C/Rm. 305, Yoshida-konoe-cho, Sakyo-ku, Kyoto city, Kyoto, Japan, 606-8501
E-mail: ajiro.masahiko.6e(at)kyoto-u.ac.jp
Tel: +81-75-753-4341
Fax: +81-75-751-7529
- Wang X, Liu H, Ge H, Ajiro M, Sharma NR, Meyers C, Morozov P, Tuschl T, Klar A, Court D, Zheng ZM. Viral DNA Replication Orientation and hnRNPs Regulate Transcription of the Human Papillomavirus 18 Late Promoter. MBio. 2017 May 30;8(3). pii: e00713-17.
- Ngoc NB, Okuno Y, Ajiro. M, Iida K, Denawa M, Yamamoto M, Sakamoto N, Kagechika H, Hagiwara M. Retinoid derivative Tp80 exhibits anti-hepatitis C virus activity through restoration of GI-GPx expression. J Med Virol. 2017 Jul;89(7):1224-1234.
- Ajiro M, Jia R, Yang Y, Zhu J, Zheng ZM. A genome landscape of SRSF3-regulated splicing events and gene expression in human osteosarcoma U2OS cells. Nucleic Acids Res. 2016 Feb 29;44(4):1854-70.
- Ajiro M, Tang S, Doorbar J and Zheng, ZM. Serine/arginine-rich splicing factor 3 and heterogeneous nuclear ribonucleoprotein A1 regulate alternative RNA splicing and gene expression of human papillomavirus type 18 through two functionally distinguishable cis-elements. J Virol. 2016 Sep 29;90(20):9138-52.
- Wang P, Zhou Z, Hu A, de Albuquerque CP, Zhou Y, Hong L, Sierecki E, Ajiro M, Kruhlak M, Harris C, Guan CL, Zheng ZM, Newton AC, Sun P, Zhou H, and Fu XD. Both decreased and increased SRPK1 levels promote cancer by interfering with PHLPP-mediated dephosphorylation of Akt. Molecular Cell, 2014, 54: 1-14.