6875 Boulevard LaSalle
Researcher, Douglas Research Centre
Group Leader, Douglas Group for Sleep and Biological Rhythms
Full Professor, Department of Psychiatry, McGill University
Associate Member, Department of Physiology, McGill University
Associate Member, Department of Microbiology and Immunology, McGill University
Associate Member, Department of Neurology and Neurosurgery, McGill University
Many physiological processes present near-24h oscillations, even in constant conditions (e.g. hormones, metabolism, cognition). These daily rhythms are called circadian rhythms, and they are generated by clocks located in most organs and cells throughout the body. The research in the Laboratory of Molecular Chronobiology aims at deciphering how these clocks work, and more specifically, to find an answer to three questions: What are the mechanisms or gears of these biological clocks? How can these clocks control physiology? How can dysfunction of these clocks lead to diseases?
1. The identification and study of clock components
Using a combination of molecular, cellular and behavioural approaches, we study the molecular bases of circadian clocks. Previously, we identified a family of nuclear receptors (REVERB and ROR) as components of the circadian clock. More recently, we have identified the deubiquitinase USP2 as a new component of the clock, and the characterization of mice lacking this protein allows us to better define the links between the clocks, environmental light and behaviour.
2. The circadian control of the immune response and infectious diseases
We study how the circadian clocks control our immune system according to the time of day. In collaboration with Dr. Nathalie Labrecque (Université de Montréal), we found that the response to vaccination varies according to time of day. When mice receive this treatment in the middle of the day, their T cells respond more strongly to antigen presentation than at any other times of day or night. What is the impact of rhythms in the immune system for the fight against infectious diseases? In collaboration with Dr. Martin Olivier (McGill University), we study this question in the context of parasitic infections, and showed that the immune response to Leishmania parasites varies according to the time of day at which the parasite is inoculated in mice.
3. Circadian disruption and schizophrenia
Up to 80% of patients with schizophrenia show disrupted sleep and circadian rhythms. In collaboration with Dr. Lalit Srivastava (Douglas Research Centre, McGill University), we study the cause of this circadian rhythm disruption, and we wonder whether these disrupted rhythms worsen schizophrenia symptoms, or act as a risk factor for the disease. For example, we showed that mice with a mutation in a gene associated with schizophrenia present abnormal circadian rhythms, and that lighting conditions that disrupt the mouse circadian rhythms exacerbate certain schizophrenia-related behaviours in the mutant mice.
4. The regulation of human circadian clocks
In order to study the regulation of human circadian clocks, we teamed up with Dr. Diane Boivin (Douglas Research Centre, McGill University). We showed that similarly to the central clock, human peripheral clocks do not adapt well to a night shift, and that light treatment as well as a pharmacological treatment can adjust these peripheral rhythms. We also looked at clock gene expression in post-mortem brain tissue, and found that rhythms of clock gene RNAs differed between the brains of Alzheimer’s disease patients compared to those of control subjects.
Nobis, C.C., Dubeau Laramée, G., Kervezee, L., Maurice De Sousa, D., Labrecque, N., Cermakian, N. (2019) The circadian clock of CD8 T cells modulates their early response to vaccination and the rhythmicity of related signaling pathways. Proc Natl Acad Sci USA, 116(40):20077-20086.
Koshy, A., Cuesta, M., Boudreau, P., Cermakian, N.#, Boivin, D.B.# (2019) Disruption of central and peripheral circadian clocks in police officers working at night. FASEB Journal, 2019 Feb 27:fj201801889R. doi: 10.1096/fj.201801889R.
Nobis, C.C., Labrecque, N., Cermakian, N. (2018) From immune homeostasis to inflammation, a question of rhythms. Current Opinion in Physiology, 5:90-98. NB: Invited peer-reviewed review article.
Kervezee, L., Cuesta, M., Cermakian, N.#, Boivin, D.B.# (2018) Simulated night shift work induces circadian misalignment of the human peripheral blood mononuclear cell transcriptome. Proc Natl Acad Sci USA, 115(21):5540-5545.
Kiessling, S., Dubeau-Laramée, G., Ohm, H., Labrecque, N., Olivier, M., Cermakian, N. (2017) The circadian clock in immune cells controls the magnitude of Leishmania parasite infection. Scientific Reports, 7:10892.
Kiessling, S., Beaulieu-Laroche, L., Blum, I., Landgraf, D., Welsh, D.K., Storch, K.F., Labrecque, N., Cermakian, N. (2017) Enhancing circadian clock function in cancer cells inhibits tumor growth. BMC Biology, 15:13.
Cuesta, M., Boudreau, P., Dubeau-Laramée, G., Cermakian, N., Boivin, D.B. (2016) Simulated night shift disrupts circadian rhythms of immune functions in humans. Journal of Immunology, 196(6):2466-75.
Labrecque, N., Cermakian, N. (2015) Circadian clocks in the immune system. Journal of Biological Rhythms, 30(4):277-290.
Bhardwaj, S.K., Stojkovic, K., Kiessling, S., Srivastava, L.K., Cermakian, N. (2015) Constant light uncovers behavioral effects of a mutation in the schizophrenia risk gene Dtnbp1 in mice. Behavioural Brain Research, 284:58-68.
Cuesta M, Cermakian N, Boivin DB. Glucocorticoids entrain molecular clock components in human peripheral cells. FASEB J. 2015;29(4):1360-70. Stojkovic, K., Wing, S.S., Cermakian, N. (2014) A central role for ubiquitination within a circadian clock protein modification code. Frontiers in Molecular Neuroscience, 7:69.
Cermakian, N., Lange, T., Golombek, D., Sarkar, D., Nakao, A., Shibata, S., Mazzoccoli, G. (2013) Cross-talk between the circadian clock circuitry and the immune system. Chronobiology International, 30(7):870-888.
Westfall, S., Aguilar-Valles, A., Mongrain, V., Luheshi, G.N., Cermakian, N. (2013) Time-dependent effects of localized inflammation on peripheral clock gene expression in rats. PLoS ONE, 8(3):e59808.
Yang, Y., Duguay, D., Bédard, N., Rachalski, A., Baquiran, G., Na, C.H., Storch, K.F., Peng, J., Wing, S.S., Cermakian, N. (2012) Regulation of behavioral circadian rhythms and clock protein PER1 by the deubiquitinating enzyme USP2. Biology Open, 1:789-801, doi:10.1242/bio.20121990.
Fortier, E.E., Rooney, J., Dardente, H., Hardy, M.P., Labrecque, N., Cermakian, N. (2011) Circadian variation of the response of T cells to antigen. Journal of Immunology, 187(12):6291-300. Epub 2011 Nov 9.
Dufour, C.R., Pham, N.H.H., Levasseur, M.P., Eichner, L.J., Wilson, B.J., Duguay, D., Poirier-Héon, J.F., Cermakian, N., Giguère, V. (2011) Genomic convergence between ERR?, PROX1 and BMAL1 in circadian control of metabolism. PLoS Genetics, 7(6):e1002143.
Cermakian, N., Waddington Lamont, E., Boudreau, P., Boivin, D.B. (2011) Circadian clock gene expression in brain regions of Alzheimer's disease patients and control subjects. Journal of Biological Rhythms, 26(2):160-170. Duguay, D., Cermakian, N. (2009) The crosstalk between physiology and circadian clock proteins. Chronobiology International, 26(8):1479-1513.
Mongrain, V., Ruan, X., Dardente, H., Fortier, E.E., Cermakian, N. (2008) Clock-dependent and independent transcriptional control of the two isoforms from the mouse Ror? gene. Genes to Cells, 13(12):1197-1210.
James, F.O., Boivin, D.B., Charbonneau, S., Bélanger, V., Cermakian, N. (2007) Expression of clock genes in human peripheral blood mononuclear cells throughout the sleep/wake and circadian cycles. Chronobiology International, 24(6):1009-1034.
James, F.O., Cermakian, N., Boivin, D.B. (2007) Circadian rhythms of melatonin, cortisol and clock gene expression to during simulated night shift work. Sleep, 30(11):1427-1436.
Dardente, H., Fortier, E.E., Martineau, V., Cermakian, N. (2007) CRYPTOCHROMES impair phosphorylation of transcriptional activators in the clock: a general mechanism for circadian repression. Biochemical Journal, 402(3):525-536.
Honouree on the 2016-17 Faculty Honour List for Educational Excellence, Faculty of Medicine, McGill University
Fonds de la recherche en santé du Québec (FRSQ) salary award (Senior), 2011-14.
John R. & Clara M. Fraser Memorial Award, McGill University Faculty of Medicine, 2010-11.
Dean's Research Recognition Award, McGill University Faculty of Medicine, 2007.
Fonds de la recherche en santé du Québec (FRSQ) salary award (Junior 2), 2006-10.
Heinz Lehmann Award from the Douglas Hospital Foundation and Pfizer Canada Inc., 2006.
Fonds de la recherche en santé du Québec (FRSQ) salary award (Junior 1), 2002-06.
Geneviève Dubeau Laramée, Research Assistant
Jhenkruthi Vijaya Shankara, Postdoctoral Fellow
Tara Delorme, PhD Student
Shashank Srikanta, PhD Student
Priscilla Cabral, PhD Student
Marie-Ève Cloutier, MSc Student
The circadian clock of CD8 T cells modulates their early response to vaccination and the rhythmicity of related signaling pathways. Proc Natl Acad Sci USA. 2019;116(40):20077-20086.
Individual metabolomic signatures of circadian misalignment during simulated night shifts in humans. PLoS Biol. 2019;17(6):e3000303.
The Phase-Shifting Effect of Bright Light Exposure on Circadian Rhythmicity in the Human Transcriptome. J Biol Rhythms. 2019:748730418821776.
Simulated night shift work induces circadian misalignment of the human peripheral blood mononuclear cell transcriptome. Proc Natl Acad Sci USA. 2018;115(21):5540-5545.
Regulation of the Neuroligin-1 Gene by Clock Transcription Factors. J Biol Rhythms. 2018;33(2):166-178.
Rapid resetting of human peripheral clocks by phototherapy during simulated night shift work. Sci Rep. 2017;7(1):16310.
The tumor circadian clock: a new target for cancer therapy? Future Oncol. 2017;13(29):2607-2610.
The circadian clock in immune cells controls the magnitude of Leishmania parasite infection. Sci Rep. 2017;7(1):10892.
PRL2 links magnesium flux and sex-dependent circadian metabolic rhythms. JCI Insight. 2017;2(13).
Skin Temperature Rhythms in Humans Respond to Changes in the Timing of Sleep and Light. J Biol Rhythms. 2017;32(3):257-273.
Enhancing circadian clock function in cancer cells inhibits tumor growth. BMC Biol. 2017;15(1):13.
The mood stabilizer valproic acid opposes the effects of dopamine on circadian rhythms. Neuropharmacology. 2016;107:262-70.
Simulated Night Shift Disrupts Circadian Rhythms of Immune Functions in Humans. J Immunol. 2016;196(6):2466-75.
EphA4 is Involved in Sleep Regulation but Not in the Electrophysiological Response to Sleep Deprivation. Sleep. 2016;39(3):613-24.
Circadian Clocks in the Immune System. J Biol Rhythms. 2015;30(4):277-90.
Constant light uncovers behavioral effects of a mutation in the schizophrenia risk gene Dtnbp1 in mice. Behav Brain Res. 2015;284:58-68.
Glucocorticoids entrain molecular clock components in human peripheral cells. FASEB J. 2015;29(4):1360-70.
Amphetamine in adolescence disrupts the development of medial prefrontal cortex dopamine connectivity in a DCC-dependent manner. Neuropsychopharmacology. 2015;40(5):1101-12.
USP2 regulates the intracellular localization of PER1 and circadian gene expression. J Biol Rhythms. 2014;29(4):243-56.
A central role for ubiquitination within a circadian clock protein modification code. Front Mol Neurosci. 2014;7:69.
Circadian clocks and inflammation: reciprocal regulation and shared mediators. Arch Immunol Ther Exp (Warsz). 2014;62(4):303-18.