Molecular Ligand Target Research Team
Team Leader
Charles M. Boone
- Brief resume
- 1989
- Ph.D., McGill University, Canada
- 1993
- Assistant Professor, Simon Fraser University, Canada
- 1997
- Assistant Professor, Queen's University, Canada
- 2000
- Associate Professor, University of Toronto, Canada
- 2003
- Professor, University of Toronto, Canada
- 2008
- Senior Visiting Scientist, RIKEN
- 2009
- Team Leader, Molecular Ligand Target Research Team, RIKEN (-current)
Outline
Small molecular ligands with unique activities must have specific target molecules that exist in their cells or organisms. Identification of the target molecules is critical for elucidating the mode of action of the molecular ligands and for drug development. However, drug target identification has been difficult in general, because the mode of interactions between the molecular ligands and their targets is not uniform. Our team aims at developing innovative techniques based on global analysis of yeast genetic interaction and physical interaction using mass spectrometry, which leads to quick and accurate detection of the ligand-target interactions. Furthermore, novel assay systems for mode-of-action studies based on protein post-translational modifications and epigenetics will be established.
Recent Research Topic
- Fig. 1: A microarray-based method for identification of drug targets using the fission yeast ORFeome
- We created a novel strain collection in a drug-sensitive genetic background that expresses the entire fission yeast ORFeome. We can now pool this library and grow the yeast in the presence of a drug. The abundance of each strain is assessed using DNA microarray to generate a genome-wide profile of drug-gene interactions. This chemical genomics approach can rapidly determine genes involved in pathways targeted by small molecules.
Selected Publications
- D. E. Williams, et al. Padanamides A and B, highly modified linear tetrapeptides produced in culture by a Streptomyces sp. isolated from a marine sediment. Org. Lett. 2011, 13, 3936.
- K. H. Seong, et al. Inheritance of stress-induced, ATF-2-dependent epigenetic change. Cell 2011, 145, 1049.
- Y. Arita, et al. Microarray-based target identification using drug hypersensitive fission yeast expressing ORFeome. Mol. BioSyst. 2011, 7, 1463.
- CH. Ho, et al. Combining functional genomics and chemical biology to identify targets of bioactive compounds, Curr. Opin. Chem. Biol. 2011, 15, 66.
- S. Nishimura, et al. Marine antifungal theonellamides target 3beta-hydroxysterol to activate Rho1 signaling, Nature Chem. Biol. 2010, 6, 519.
- T. Maekawa, W. Jin, S. Ishii, The role of ATF-2 family transcription factors in adipocyte differentiation: antiobesity effects of p38 inhibitors, Mol. Cell. Biol. 2010, 30, 613.
- T. Maekawa, et al. Social isolation stress induces ATF-7 phosphorylation and impairs silencing of the 5-HT 5B receptor gene, EMBO J. 2010, 29, 196.
- K. Sasaki, T. Ito, N. Nishino, S. Khochbin, M. Yoshida, Real-time imaging of histone H4 hyperacetylation in living cells, Proc. Natl. Acad. Sci. USA 2009, 106, 16257.
- CH. Ho, et al. A molecular barcoded yeast ORF library enables mode-of-action analysis of bioactive compounds, Nature Biotechnol. 2009, 27, 369.
- A. Shirai, et al. Global analysis of gel mobility of proteins and its use in target identification, J. Biol. Chem. 2008, 283, 10745.
- Y. Yashiroda, A. Matsuyama, M. Yoshida, New insights into chemical biology from ORFeome libraries, Curr. Opin. Chem. Biol. 2008, 12, 55.
Core Members
| Principal Investigator |
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| Charles M. Boone |
Team Leader |
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| Postdoctoral Fellow |
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| Jeffrey Scott Piotrowski |
Foreign Postdoctoral Researcher |
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| Student Trainee |
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| Technical Assistant |
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| Administrative Assistant |
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| Visiting Research Staff |
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( ) indicates primary affiliation in RIKEN.
