Circadian (~24 h) rhythmicity is a fundamental property of nearly all living beings on this planet. In mammals, the master pace maker is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN relays photic information from the retina to the brain to synchronize endogenous rhythms to ambient light/dark cycles. Desynchronization of the endogenous rhythms can lead to fatigue, insomnia and memory loss as seen in jet lag. Circadian clocks also exist in a variety of extra-SCN regions throughout the brain. The rhythms in these regions modulate brain activities on a daily basis. A variety of neurophysiological processes are rhythmically regulated by the circadian clock, which accounts for the time-of-day variations in our sensory, motor, memory and social functions. Conversely, disruption of circadian rhythms has been reported in patients with neurological and psychiatric disorders. My lab is interested in molecular signaling mechanisms that orchestrate daily rhythms in our brain and how their dysregulation contributes to various brain diseases. We are particularly interested in the role of mammalian target of rapamycin (mTOR) signaling and mechanisms that control mRNA translation in the brain. The lab utilizes a combination of molecular, cellular and behavioral technologies, including polysome profiling, RNA sequencing, qRT-PCR, Western blotting, immunocytochemistry, electrophysiology, confocal microscopy, viral-mediated gene silencing and animal behavioral analysis (e.g., circadian, social and memory tests, EEG). A variety of model systems, including cell culture, organotypic slice culture, and whole animals (transgenic and knockout mice) are employed. We constantly look for talented and motivated graduate students to join our lab.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
Cao R, Gkogkas CG, de Zavalia N, Blum ID, Yanagiya A, Tsukumo Y, Xu H, Lee C, Storch KF, Liu AC, Amir S, Sonenberg N (2015). Light-regulated translational control of circadian behavior by eIF4E phosphorylation. Nature Neuroscience, 18(6):855-62.
*Gkogkas CG, *Khoutorsky A, Cao R, Giannakas N, Kaminari A, Aguilar-Valles A, Fragkouli A, Nader K, Konicek BW, Graff JR, Tzinia AK, Lacaille JC, Sonenberg N (2014). Pharmacogenetic inhibition of eIF4E-dependent Mmp9 mRNA translation reverses Fragile-X syndrome-like phenotypes. Cell Reports, 9(5):1742-55. *equal contribution
Cao R, Robinson B, Xu H, Gkogkas C, Khoutorsky A, Alain T, Yanagiya A, Nevarko T, Liu AC, Amir S, Sonenberg N (2013). Translational control of entrainment and synchrony of the suprachiasmatic circadian clock by mTOR/4E-BP1 signaling. Neuron, 79(4):712-24.
Cao R, Li A, Cho HY, Lee B, Obrietan K (2010). mammalian target of rapamycin signaling modulates photic entrainment of the suprachiasmatic circadian clock. Journal of Neuroscience, 30(18): 6302-14.
Cao R, Li A, Cho HY (2009). mTOR signaling in epileptogenesis: too much of a good thing? Journal of Neuroscience, 29(40):12372-73.
Cao R, Anderson FE, Jung YJ, Dziema H, Obrietan K (2011). Circadian regulation of mTOR signaling in the mouse suprachiasmatic nucleus. Neuroscience, 181:79-88.
Cao R, Lee B, Cho HY, Saklayen S, Obrietan K (2008). Photic regulation of the mTOR signaling pathway in the suprachiasmatic circadian clock. Molecular and Cellular Neuroscience, 38(3):312-24.
Cao R, Hasuo H, Ooba S, Akasu T, Zhang X (2006). Facilitation of glutamatergic synaptic transmission in hippocampal CA1 area of rats with traumatic brain injury. Neuroscience Letters, 401(1-2):136-41.
Lee B, Cao R, Choi YS, Cho HY, Rhee AD, Hah CK, Hoyt KR, Obrietan K (2009). The CREB/CRE transcriptional pathway: protection against oxidative stress-mediated neuronal cell death. Journal of Neurochemistry, 108(5):1251-65.