Molecular Ligand Target Research Team
Team Leader
Charles M.BOONE (Ph.D.)
Small molecular ligands with unique activities must have the 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.
- Global analysis of genetic and physical interaction between molecular ligands and their target molecules
- Mode of action of bioactive compounds
- Identification and characterization of target proteins that interact with molecular ligands using mass and NMR spectrometry
- Andrusiak, K., Piotrowski, JS., and Boone, C.:
"Chemical-genomic profiling: systematic analysis of the cellular targets of bioactive molecules."
Bioorg, Med. Chem. in press. - Seong, KH., Li, D., Shimizu, H., Nakamura, R., and Ishii, S.:
"Inheritance of stress-induced, ATF-2-dependent epigenetic change."
Cell, 145: 1049-1061, 2011. - Staton, TL., Lazarevic, V., Jones, DC., Lanser, AJ., Takagi, T., Ishii, S., and Glimcher, LH.:
"Dampening of death pathways by schnurri-2 is essential for T-cell development."
Nature, 472: 105-109, 2011. - Williams, DE., Dalisay, DS., Patrick, BO., Matainaho T., Andrusiak, K., Deshpande, R., Myers, CL., Piotrowski, JS., Boone, C., Yoshida, M., and Andersen, RJ.:
"Padanamides A and B, highly modified linear tetrapeptides produced in culture by a Streptomyces sp. isolated from marine sediment collected in Papua New Guinea."
Org. Lett., 13: 3936-3939, 2011. - Arita, Y., Nishimura, S., Matsuyama, A., Yashiroda, Y., Usui, T., Boone, C., and Yoshida, M.:
"Microarray-based target identification using drug hypersensitive fission yeast expressing ORFeome."
Mol. Biosyst., 7: 1463-1472, 2011. - Piotrowski, JS., Ho, CH., and Boone, C.:
"The awesome power of synergy from chemical-chemical profiling."
Chem. Biol., 17: 789-790, 2010. - Nishimura, S., Arita, Y., Honda, M., Iwamoto, K., Matsuyama, A., Shirai, A., Kawasaki, H., Kakeya, H., Kobayashi, T., Matsunaga, S., and Yoshida, M.:
"Marine antifungal theonellamides target 3beta-hydroxysterol to activate Rho1 signaling."
Nat. Chem. Biol., 6: 519-526, 2010. - Maekawa, T., Jin, W., and Ishii, S.:
"The role of ATF-2 family transcription factors in adipocyte differentiation: antiobesity effects of p38 inhibitors."
Mol. Cell. Biol., 30: 613-625, 2010. - Maekawa, T., Kim, S., Nakai, D., Makino, C, Takagi, T., Ogura, H., Yamada, K., Chatton, B., and Ishii, S.:
"Social isolation stress induces ATF-7 phosphorylation and impairs silencing of the 5-HT 5B receptor gene."
EMBO J., 29: 196-208, 2010. - Ho, CH., Magtanong, L., Barker, SL., Gresham, D., Nishimura, S., Natarajan, P., Koh, JL., Porter, J., Gray, CA., Andersen, RJ., Giaever, G., Nislow, C., Andrews, B., Botstein, D., Graham, TR., Yoshida, M., and Boone, C.:
"A molecular barcoded yeast ORF library enables mode-of-action analysis of bioactive compounds."
Nat. Biotechnol., 27: 369-377, 2009.
Principal Investigator
- Charles M BOONE
- Team Leader
Staff Scientist
- Yoko YASHIRODA
- Senior Research Scientist
- Akihiro ITO
- Senior Research Scientist
Postdoctoral Fellow
- Jeffrey Scott PIOTROWSKI
- Foreign Postdoctoral Researcher