Winner of FAOBMB Entrepreneurship Award 2017

Winner of 2017 FAOBMB Entrepreneurship Award: Professor Masatoshi Hagiwara (Japan)

Professor Masatoshi Hagiwara

  1. Successful scientific career

Masatoshi Hagiwara was born in Mie prefecture, Japan and entered into Mie University School of Medicine in 1978. In his Ph.D. work, he uncovered the inhibitory mechanism of isoquinolinesulfonamide compounds on protein kinases. Based on that finding, he succeeded to develop specific kinase inhibitors such as H-89, KN62, and CKI-7. One of the isoquinolinesulfonamides, fasudil, was developed as a clinical drug against subarachnoid haemorrhage. When he was a postdoctoral fellow in Marc Montminy’s laboratory in the Salk Institute (USA), he found that transcriptional attenuation following cAMP induction requires PP-1-mediated dephosphorylation of CREB (Hagiwara et al., Cell 1992). In addition, he succeeded to identify CBP as the phosphorylated CREB binding protein in collaboration with R. Goodman’s group (Chrivia et al., Nature 1993).

When he returned to Japan in 1993, Hagiwara started his own laboratory in the Nagoya University School of Medicine as an Assistant Professor. He moved to Tokyo in 1997 as a Professor of the Medical Research Institute of Tokyo Medical and Dental University, and decided to try to decipher the splicing code to cure some genetic diseases. He moved from Tokyo to Kyoto University in 2010 as Professor and became Chairman of the Department of Anatomy and Developmental Biology in the Graduate School of Medicine.

  1. Translation of research technology to the scientific community

The main objective of Prof. Hagiwara’s research is to develop novel therapeutic methods manipulating transcriptome with small chemicals to cure genetic diseases. To realize the objective, his laboratory has developed original cell-based assay technologies. Initially he succeeded to visualize the activation steps of a transcription factor CREB in living cells by producing a phospho-specific antibody of CREB (Hagiwara et al., MCB 1993). They further developed a fluorescence resonance energy transfer (FRET) method for visualizing phosphorylation of proteins in living cells using a novel fluorescent indicator composed of two green fluorescent protein (GFP) variants joined by the kinase-inducible domain (KID) of CREB (Nagai et al, Nat Biotech 2000). Then, they succeeded to visualize tissue-specific and developmental-stage-specific alternative splicing patterns in living nematode worms, and identified the regulatory factors by genomic mapping of the mutants (Kuroyanagi et al., Nat Methods 2006). The “color-changing worms” received worldwide attention, and their unique method was introduced in an article of Nature Reviews. To share the newly developed techniques with other researchers of this field, detailed protocols were published (Kuroyanagi et al., Nat Protocols 2010). They further developed the splicing reporter technology, established a dual-color splicing reporter screening system called SPREADD (splicing reporter assay for disease genes with dual-color), applied this to aberrant splicing of IKBKAP exon 20 found in FD patients due to the intronic mutation (IVS20+6T>C), and identified a compound RECTAS that efficiently corrects the mis-splicing of IKBKAP (Yoshida et al. PNAS 2015).

  1. Translation to the commercial world

To realize the new therapeutics and rescue patients who suffer incurable disease, Prof. Hagiwara started his own venture company Kinopharma Co Ltd. in 2005 as an entrepreneur. In cooperation with Kinopharma, he has developed an anti-virus drug FIT039 targeting host factors required for virus proliferation. FIT039 specifically inhibits CDK9 and suppresses viral transcription of a broad spectrum of DNA viruses including HCMV, HAdV, HBV and HPV without significant adverse effect on mammalian cells (Yamamoto et al. J Clin Invest. 2014). Thus, the phase1/2a clinical trial of FIT039 is under way in Kyoto University Hospital for the patients of skin warts caused by Human papilloma virus. The clinical trial for cervical cancer of uterus with this anti-virus drug is also being readied to start soon.

  1. Entrepreneurial outcomes in broader aspects of science and technology

To promote the collaboration network between biological/medical scientists and synthetic chemists in Japan, Hagiwara contributed to the organization of the Japanese Society of Chemical Biology (JSCB), which was founded in 2005. As the first Secretary General of JSCB, he negotiated with Japanese government to make a public chemical library. Since 2011, he became the President of JSCB and he has contributed to the development of the new scientific field in cooperation with Chemical Society, Society of Pharmacology, Biochemical Society, Molecular Biology Society, Cell Biology Society in Japan. The number of members of JSCB is now over 1,400. To expand the cooperation outside Japan, he participated in the establishment of the International Chemical Biology Society (ICBS) as one of founding members. He organized the annual meeting of ICBS in 2013 at Kyoto and had the role of President of ICBS in 2013-2014.

  1. Contributions to Science and Society:

As Director General of Kyoto University Medical Science and Business Liaison (KUMBL), he is now contributing in a major way to the promotion of translational research in the Medical School of Kyoto University. In this position, he oversees technology transfer and the incubation of academic ventures. In 2016, KUMBL started a highly significant international venture through the Kyoto-SPARK program in cooperation with Stanford University (USA) to promote translational research for young scientists.

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