个人简介

B.S., University of Washington Ph.D., University of North Carolina, Chapel Hill Postdoctoral Fellow, University of Texas Southwestern Medical Center

研究领域

Biochemistry and biophysics, nuclear magnetic resonance spectroscopy; molecular mechanism of circadian rhythmicity

Nearly all eukaryotic organisms have molecular clocks that synchronize their physiological processes into rhythms that coincide with the solar day, providing enhanced evolutionary fitness by optimizing energy utilization and coordinating the timing of integrated biochemical processes. Disruption of these circadian rhythms in mouse models causes adverse effects by affecting the etiology of psychiatric disorders, diabetes, cardiovascular disease, and cancer. In mammals, the self-sustaining circadian oscillator is generated by a set of integral ‘clock proteins’ in a transcription/translation feedback loop, which exerts its control on physiology and behavior by gating transcriptional regulation of nearly 15% of the genome with its 24-hour periodicity. The cell-autonomous daily period of this oscillator arises from the tightly regulated posttranslational modification of its state variable, the Period (PER) protein, which controls this dynamic system by serving as a scaffold to coordinate clock protein complexes. Recent studies have demonstrated an unexpected regulation of the clock by metabolic and genomic surveillance pathways that directly modulate PER activity to control clock timing. Through reciprocal regulation of PER activity, the clock and DNA damage checkpoint provide temporal regulation of cellular proliferation and genomic integrity. Our goal is to identify the fundamental basis of crosstalk between the circadian clock and DNA damage checkpoint response to understand how disruption of the clock regulates oncogenesis. We will achieve this by integrating diverse experimental approaches from cell biology to solution NMR spectroscopy to gain an atomic-level understanding of the clock, as well as providing new targets and/or a temporal basis for improved therapeutic intervention in cancer.

近期论文

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Mukherjee, S., Partch, C.L., Derebe, M., Rollins, D., Gardner, K., Rizo-Rey, J., Jiang, Q.-X., Hooper, L.V. (2011) An intestinal C-type lectin kills bacteria through formation of a membrane-penetrating pore, Manuscript in preparation Partch, C.L. and Gardner, K.H. (2011) Coactivators necessary for transcriptional output of the hypoxia inducible factor, HIF, are directly recruited by ARNT PAS-B. Proc Natl Acad Sci USA 108: 7739-44 Motta-Mena, L.B., Partch, C.L., Gardner, K.H. (2010) The three Rs of transcription: recruit, retain, recycle Mol Cell 40: 855-58 Lehotzky, R.E.*, Partch, C.L.*, Mukherjee, S., Cash, H., Goldman, W.E., Gardner, K.H., Hooper, L.V. (2010) Molecular basis for peptidoglycan recognition by a bactericidal lectin. Proc Natl Acad Sci USA 107: 7722-7 Partch, C.L. and Gardner, K.H. (2010) Coactivator recruitment: a new role for PAS domains in transcriptional regulation by the bHLH-PAS family. J Cell Physiol 223: 553-7 Partch, C.L., Card, P.B., Amezcua, C.A., Gardner, K.H. (2009) Molecular basis of coiled coil coactivator recruitment by the aryl hydrocarbon receptor nuclear translocator (ARNT). J Biol Chem 284: 15184-92 Mukherjee, S.*, Partch, C.L.*, Lehotzky, R.E., Whitham, C., Chu, H., Bevins, C., Gardner, K.H., Hooper, L.V. (2009) Regulation of C-type lectin antimicrobial activity by a flexible N-terminal propeptide. J Biol Chem 284: 4881-86 Öztürk, N., Song, S., Özgür, S., Selby, C.P., Morrison, L., Partch, C.L., Zhong, D., Sancar, A. (2007) Structure and function of animal crytochromes. Cold Spring Harbor Symposium on Clocks and Rhythms 72: 119-131 Huang, Y., Baxter, R., Smith, B.S., Partch, C.L., Colbert, C.L., Deisenhofer, J. (2006) Crystal structure of cryptochrome 3 from Arabidopsis thaliana: a novel MTHF binding mode and implications for photolyase activity. Proc Natl Acad Sci USA 103: 17701-06 Partch, C.L., Shields, K.F., Thompson, C.L., Selby, C.P., Sancar, A. (2005) Posttranslational regulation of the mammalian circadian clock by cryptochrome and protein phosphatase 5. Proc Natl Acad Sci USA 103: 10467-72 Partch, C.L. and Sancar, A. (2005) Photochemistry and photobiology of cryptochrome blue-light photopigments: The search for a photocycle. Photochem Photobiol 81: 1291-1304 Partch, C.L., Clarkson, M.W., Özgür, S., Lee, A.L., Sancar, A. (2005) Role of structural plasticity in signal transduction by the cryptochrome blue-light photoreceptor. Biochemistry 44: 3795-3805 Partch, C.L. and Sancar, A. (2005) Cryptochromes and circadian photoreception in animals. Methods Enzymol, Circadian Rhythms, Young, M.W. ed., Elsevier Science, Vol. 393, p. 724-743