About Professor Shiroh FUTAKI
Professor of Biochemistry
Institute for Chemical Research
Professor Shiroh Futaki graduated from Faculty of Pharmaceutical Sciences, Kyoto University in 1983 and obtained his Ph.D. in Pharmaceutical Sciences in 1989 from Kyoto University under the supervision of Professors Haruaki YAJIMA and Nobutaka FUJII. Meanwhile he was appointed as a Research Associate at Faculty of Pharmaceutical Sciences, The University of Tokushima in 1987. His postdoctoral training was with Professor James MANNING at The Rockefeller University, New York City (1989-1991). He was promoted to Associate Professor at Faculty of Pharmaceutical Sciences, The University of Tokushima in 1993. He moved to Institute of Chemical Research, Kyoto University as an Associate Professor in 1997 and he was then promoted to a Full Professor of Biochemistry in 2005. He was also appointed as a PREST and SORST Investigator of JST from 2003 to 2006, and from 2006 to 2008, respectively. He visited Université Pierre et Marie Curie, Paris as a professeur invité in 2010. He is now a Trustee of The Japanese Peptide Society and also an Associate Editor of Molecular Therapy and a member in the Editorial Boards of 4 scientific journals. His honors include The Japanese Peptide Society Award for Young Scientists (1997), Daiichi Pharmaceutical Award in Synthetic Organic Chemistry, Japan (1997), and The Pharmaceutical Society of Japan Award for Young Scientists (1998).
Our Principal Research Interests:
1. Development of cell-penetrating peptide vectors and elucidation of the internalization mechanisms
Arginine-rich cell-penetrating peptides are an attractive means of intracellular delivery of therapeutic molecules. This has also potential in chemical and biological studies on cellular functions. Using designed peptides as an analytical tool, we are exploring the methods of internalization of arginine-rich peptides and developing novel efficient and effective means for intracellular delivery.
1) Nakase et al., Cell-surface accumulation of flock house virus-derived peptide leads to efficient internalization via macropinocytosis. Mol. Ther. 2009, 17, 1868-76
2) Inomata et al., High-resolution multi-dimensional NMR spectroscopy of proteins in human cells. Nature 2009, 458, 106-9
3) Kosuge et al., Cellular internalization and distribution of arginine-rich peptides as a function of extracellular peptide concentration, serum, and plasma membrane associated proteoglycans. Bioconjug. Chem. 2008 19, 656-64
4) Nakase I, et al., Methodological and cellular aspects that govern the internalization mechanisms of arginine-rich cell-penetrating peptides. Adv. Drug Deliv. Rev. 2008, 60, 598-607.
5) Nakase et al., Interaction of arginine-rich peptides with membrane-associated proteoglycans is crucial for induction of actin organization and macropinocytosis. Biochemistry 2007, 46, 492-501
6) Takeuchi et al., Direct and rapid cytosolic delivery using cell-penetrating peptides mediated by pyrenebutyrate. ACS Chem. Biol. 2006, 1, 299-303.
2. Design of novel membrane-interacting peptides
We are also developing novel peptides that have an ability to interact with biological membranes in concert with external signals or cellular conditions. We have also interests in creating artificial ligand-gated ion channels. These approaches should have impact for the creation of novel systems for drug delivery, sensing and cell manipulation.
1) Kobayashi et al., Cytosolic targeting of macromolecules using a pH-dependent fusogenic peptide in combination with cationic liposomes. Bioconjug. Chem. 2009, 20, 953-9.
2) Noshiro et al., Metal-assisted channel stabilization: disposition of a single histidine on the N-terminus of alamethicin yields channels with extraordinarily long lifetimes. Biophys. J. 2010, 98, 1801-8.
3) Kiwada et al., Transmission of extramembrane conformational change into current: construction of metal-gated ion channel. J. Am. Chem. Soc. 2006, 128, 6010-1.
3. Design and creation of bioactive proteins that regulate cell function and genes
Another challenge in our laboratory includes creation of artificial DNA-binding and gene-regulation systems. These systems should be beneficial for the understanding of cell functions as well as controlling biological systems.
1) Imanishi et al., Metal-stimulated regulation of transcription by an artificial zinc-finger protein. ChemBioChem 2010, 11, 1653-5.
2) Azuma et al., Cobalt(II)-responsive DNA binding of a GCN4-bZIP protein containing cysteine residues functionalized with iminodiacetic acid. Angew. Chem. Int. Ed. Engl. 2009, 48, 6853-6.