Ruifeng (Ray) Cao, MD, PhD

• Graduate Faculty, Graduate Program in Pharmacology
• Faculty, Graduate Program in Neuroscience
• Faculty, Integrated Biosciences Graduate Program
• Researcher, Masonic Cancer Center

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 disorders such as Alzheimer's disease and Parkinson’s disease.

My lab is interested in molecular signaling mechanisms that orchestrate daily rhythms in our brain and how their dysregulation contributes to various neurological and psychiatric diseases. We are particularly interested in the role of mammalian target of rapamycin (mTOR) signaling and mechanisms that control mRNA translation in the circadian clock.

We constantly look for talented and motivated undergraduate, graduate students and postdoctoral researchers to join our lab.

Liu D, Nanclares C, Simbriger K, Fang K, Lorsung E, Le N, Amorim IS, Chalkiadaki K, Pathak SS, Li J, Gewirtz JC, Jin VX, Kofuji P, Araque A, Orr HT, Gkogkas CG, Cao R. 'Autistic-like behavior and cerebellar dysfunction in Bmal1 mutant mice ameliorated by mTORC1 inhibition.' Mol Psychiatry. 2022 Mar 17. doi: 10.1038/s41380-022-01499-6. Epub ahead of print. PMID: 35301425.

Areal, CC, Cao, R, Sonenberg, N & Mongrain, V 2020, 'Wakefulness/sleep architecture and electroencephalographic activity in mice lacking the translational repressor 4E-BP1 or 4E-BP2', Sleep, vol. 43, no. 2. https://doi.org/10.1093/sleep/zsz210

Pathak, SS, Liu, D, Li, T, de Zavalia, N, Zhu, L, Li, J, Karthikeyan, R, Alain, T, Liu, AC, Storch, KF, Kaufman, RJ, Jin, VX, Amir, S, Sonenberg, N & Cao, R 2019, 'The eIF2? Kinase GCN2 Modulates Period and Rhythmicity of the Circadian Clock by Translational Control of Atf4', Neuron, vol. 104, no. 4, pp. 724-735.e6. https://doi.org/10.1016/j.neuron.2019.08.007

Aguilar-Valles, A, Haji, N, De Gregorio, D, Matta-Camacho, E, Eslamizade, MJ, Popic, J, Sharma, V, Cao, R, Rummel, C, Tanti, A, Wiebe, S, Nuñez, N, Comai, S, Nadon, R, Luheshi, G, Mechawar, N, Turecki, G, Lacaille, JC, Gobbi, G & Sonenberg, N 2018, 'Translational control of depression-like behavior via phosphorylation of eukaryotic translation initiation factor 4E' Nature communications, vol. 9, no. 1, 2459. https://doi.org/10.1038/s41467-018-04883-5

Cao, R 2018, 'mTOR signaling, translational control, and the circadian clock' Frontiers in Genetics, vol. 9, no. SEP, 367. https://doi.org/10.3389/fgene.2018.00367

Ramanathan, C, Kathale, ND, Liu, D, Lee, C, Freeman, DA, Hogenesch, JB, Cao, R & Liu, AC 2018, 'mTOR signaling regulates central and peripheral circadian clock function' PLoS Genetics, vol. 14, no. 5, e1007369. https://doi.org/10.1371/journal.pgen.1007369

Liu, D, Stowie, A, de Zavalia, N, Leise, T, Pathak, SS, Drewes, LR, Davidson, AJ, Amir, S, Sonenberg, N & Cao, R 2018, 'mTOR signaling in VIP neurons regulates circadian clock synchrony and olfaction' Proceedings of the National Academy of Sciences of the United States of America, vol. 115, no. 14, pp. E3296-E3304. https://doi.org/10.1073/pnas.1721578115

Gantois, I, Khoutorsky, A, Popic, J, Aguilar-Valles, A, Freemantle, E, Cao, R, Sharma, V, Pooters, T, Nagpal, A, Skalecka, A, Truong, VT, Wiebe, S, Groves, IA, Jafarnejad, SM, Chapat, C, McCullagh, EA, Gamache, K, Nader, K, Lacaille, JC, Gkogkas, CG & Sonenberg, N 2017, 'Metformin ameliorates core deficits in a mouse model of fragile X syndrome' Nature Medicine, vol. 23, no. 6, pp. 674-677. https://doi.org/10.1038/nm.4335

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, vol. 18, no. 6, pp. 855-862. https://doi.org/10.1038/nn.4010

Gkogkas, CG, Khoutorsky, A, Cao, R, Jafarnejad, SM, Prager-Khoutorsky, M, Giannakas, N, Kaminari, A, Fragkouli, A, Nader, K, Price, TJ, 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, vol. 9, no. 5, pp. 1742-1755. https://doi.org/10.1016/j.celrep.2014.10.064

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, vol. 79, no. 4, pp. 712-724. https://doi.org/10.1016/j.neuron.2013.06.026