Molecular Control of Circadian Rhythm in Animals


Selected Publications


Oshima, T.*, Niwa, Y.* (*, equal contribution), Kuwata, K., Srivastava, A., Hyoda, T., Tsuchiya, Y., Kumagai, M., Tsuyuguchi, M., Tamaru, T., Sugiyama, A., Ono, N., Zolboot, N., Aikawa, Y., Oishi, S., Nonami, A., Arai, F., Hagihara, S., Yamaguchi, J., Tama, F., Kunisaki, Y., Yagita, K., Ikeda, M., Kinoshita, T., Kay, S.A., Itami, K.#, and Hirota, T. # (#, correspondence): Cell-based screen identifies a new potent and highly selective CK2 inhibitor for modulation of circadian rhythms and cancer cell growth.
Science Advances, 5: eaau9060 (2019)


Lee, J.W.*,#, Hirota, T.,*,# (*, equal contribution; #, correspondence), Ono, D., Honma, S., Honma, K.I., Park, K., and , Kay, S.A.: Chemical control of mammalian circadian behavior through dual inhibition of casein kinase Iα and δ.
J. Med. Chem., 62: 1989-1998 (2019)


Qu, M., Duffy, T., Hirota, T., and Kay, S.A.: Nuclear receptor HNF4A transrepresses CLOCK:BMAL1 and modulates tissue-specific circadian networks.
Proc. Natl. Acad. Sci. USA, 115: E12305-E12312 (2018)


Zhao, X., Hirota, T., Han, X., Cho, H., Chong, L., Lamia, K., Liu, S., Atkins, A.R., Banayo, E., Liddle, C., Yu, R.T.,
Yates III, J.R., Kay, S.A., Downes, M., and Evans, R.M.: Circadian amplitude regulation via FBXW7-targeted REV-ERBα degradation.
Cell, 165: 1644-1657 (2016)


Lee,J.W.,* Hirota, T.,*,# (*, equal contribution; #, correspondence), Kumar, A.,*,#, Kim, N.J., Irle, S., and Kay, S.A.,#: Development of small molecule Cryptochrome stabilizer derivatives as modulators of the circadian clock. ChemMedChem, 10: 1489-1497 (2015)


Hirota, T. and Kay, S.A.: Identification of small-molecule modulators of the circadian clock.
Methods Enzymol., 551: 267-282 (2015)


St. John, P.C., Hirota, T., Kay, S.A., and Doyle, F.J. 3rd: Spatiotemporal separation of PER and CRY posttranslational regulation in the mammalian circadian clock.
Proc. Natl. Acad. Sci. USA, 111: 2040-2045 (2014)


Hirota, T., Lee, J.W., St. John, P.C., Sawa, M., Iwaisako, K., Noguchi, T., Pongsawakul, P.Y., Sonntag, T., Welsh, D.K., Brenner, D.A., Doyle, F.J. 3rd, Schultz, P.G., and Kay, S.A.: Identification of small molecule activators of cryptochrome.
Science, 337: 1094-1097 (2012)


Lee, J.W.*, Hirota, T.* (*; equal contribution), Peters, E.C., Garcia, M., Gonzalez, R., Cho, C.Y., Wu, X., Schultz, P.G., and Kay, S.A.: A small molecule modulates circadian rhythms through phosphorylation of the period protein.
Angew. Chem. Int. Ed., 50: 10608-10611 (2011)


Hirota, T., Lee, J.W., Lewis, W.G., Zhang, E.E., Breton, G., Liu, X., Garcia, M., Peters, E.C., Etchegaray, J.P., Traver, D., Schultz, P.G., and Kay, S.A.: High-throughput chemical screen identifies a novel potent modulator of cellular circadian rhythms and reveals CKIα as a clock regulatory kinase.
PLoS Biol., 8: e1000559 (2010)


Zhang, E.E.*, Liu, Y.*, Dentin, R., Pongsawakul, P.Y., Liu, A.C., Hirota, T., Nusinow, D.A., Sun, X., Landais, S., Kodama, Y., Brenner, D.A., Montminy, M., and Kay, S.A.: Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis.
Nat. Med., 16: 1152-1156 (2010)


Zhang, E.E.*, Liu, A.C.*, Hirota, T.* (* equal contribution), Miraglia, L.J., Welch, G., Pongsawakul, P.Y., Liu, X., Atwood, A., Huss, J.W. 3rd, Janes, J., Su, A.I., Hogenesch, J.B., and Kay, S.A.: A genome-wide RNAi screen for modifiers of the circadian clock in human cells.
Cell, 139: 199-210 (2009)


Hirota, T. and Kay, S.A.: High-throughput screening and chemical biology: new approaches for understanding circadian clock mechanisms.
Chem. Biol., 16: 921-927 (2009)


Hirota, T., Lewis, W.G., Liu, A.C., Lee, J.W., Schultz, P.G., and Kay, S.A.: A chemical biology approach reveals period shortening of the mammalian circadian clock by specific inhibition of GSK-3b.
Proc. Natl. Acad. Sci. USA, 105: 20746-20751 (2008)