The major objective of my research is to understand the molecular basis for our circadian (daily) rhythms. Circadian rhythms have been observed in nearly all organisms from cyanobacteria to humans. These rhythms are under the direct influence of environmental cues, most notably the day/night cycle, and by a genetically determined, endogenous clock called the “circadian clock.” The most familiar circadian rhythm is our own sleep/wake rhythm. However, there is circadian rhythmicity in many aspects of physiology, including alertness, activity, hormone production and drug efficacy. These and other daily activities and physiological processes are under the control of the circadian clock. The circadian clock is cell-autonomous and ubiquitously present in most tissues.

To understand the molecular mechanism of our circadian rhythms, my lab is using the mouse as a model system. Currently, we are employing biochemical and genetic techniques to discover novel clock genes and to understand the mammalian circadian clock at a molecular level. The discovery of new clock components and regulatory pathways will not only broaden our understanding of circadian physiology but also provide additional molecular handles for manipulating the clock for the treatment of human circadian disorders.

Chen, R., Schirmer, A., Lee, Y., Lee, H., Kumar, V., Yoo, S., Takahashi, J.S. and Lee, C. Rhythmic mPER abundance defines a critical nodal point for negative feedback within the circadian clock mechanism. Molecular Cell in press

Ramsey, K.M., Yoshino, J., Brace, C.S., Abrassart, D., Kobayashi, Y., Marcheva, B., Hong, H., Chong, J.L., Buhr, E.D., Lee, C., Takahashi, J.S. and Imai, S., Bass, J. (2009) Circadian Clock Feedback Cycle Through NAMPT-Mediated NAD+ Biosynthesis. Science 324:651.

Ansari, N., Agathagelidis, M., Lee, C., Korf, H. and von Gall, C. (2009) Differential maturation of circadian rhythms in clock gene proteins in the suprachiasmatic nucleus and the pars tuberalis during mouse ontogeny. European Journal of Neuroscience. 29:477-89

Chen, R., Seo, D., Bell, E., von Gall, C. and Lee, C. (2008) Strong resetting of the mammalian clock by constant light followed by constant darkness. Journal of Neuroscience. 28:1839-47

Antoch, M.P., Gorbacheva, V.Y., Vykhovanets, O., Toshkov, I.A., Kondratov, R.V., Kondratova, A.A., Lee, C. and Nikitin, A.Y. (2008) Disruption of the circadian clock due to the Clock mutation has discrete effects on aging and carcinogenesis. Cell Cycle 7:1197-204.

Siepka, S. M., Yoo, S., Park, J., Lee, C. and Takahashi, J.S. (2007) Genetics and Neurobiology of Circadian Clocks in Mammals. Cold Spring Harbor Symposia on Quantitative Biology 72:251-9.

Busino L, Bassermann F, Maiolica A, Lee C, Nolan P.M., Godinho S, Draetta G.F. and Pagano., M. (2007) SCFFbxl3 Controls the Oscillation of the Circadian Clock by Directing the Degradation of Cryptochrome Proteins. Science 316:900-4.

Siepka S.M., Yoo S, Park J, Song W, Kumar V, Hu Y, Lee C and Takahashi J.S. (2007) Circadian Mutant Overtime Reveals F-box Protein FBXL3 Regulation of Cryptochrome and Period Gene Expression. Cell 129:1011-23.

Kondratov RV, Kondratova AA, Lee C, Gorbacheva VY, Chernov MV, Antoch MP. (2006) Post-Translational Regulation of Circadian Transcriptional CLOCK(NPAS2)/BMAL1 Complex by CRYPTOCHROMES. Cell Cycle 5: 890-5.

Yoo, S.H., Ko, C., Lowrey, P., Buhr, E., Song, E.J., Chang, S., Yoo, O.J., Yamazaki, S., Lee, C. and Takahashi, J.S. (2005) A novel E-box Enhancer Drives Mouse Period2 Circadian Oscillations in vivo. PNAS 102: 2608-2613

Lee, C., Weaver, D.R., and Reppert, S.M. (2004) Direct association between mouse PERIOD and CKI? is critical for a functioning circadian clock. Molecular and Cellular Biology.24: 584-594