6875 Boulevard LaSalle
Associate Professor, Department of Psychiatry, McGill University
Associate Member, Departments of Physiology, Microbiology & Immunology, Neurology & Neurosurgery, McGill University
Researcher, Douglas Institute Research Centre
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. Clock genes, behaviour and mental health.
Using a combination of molecular, cellular and behavioural approaches, we study the molecular bases of circadian clocks. Recently, the characterization of mice knock-out for the deubiquitinase USP2 allows us to better define the links between the clocks, environmental light and behaviour. This can be put in parallel with our studies on circadian rhythms in a mouse model of schizophrenia and those on clock gene expression in psychiatric disorders.
2. Circadian rhythms and the immune system.
We study the circadian control of immune responses (in collaboration with Dr. Nathalie Labrecque, University of Montreal, Maisonneuve-Rosemont Hospital). Notably, we reported that T lymphocytes display a circadian rhythm in their response to antigens. In another study we showed that inflammation causes strong changes in clock gene expression in peripheral tissues of the rat. This project, which links chronobiology and immunology, illustrates the role of circadian clocks in the response to infections and cancer.
3. Expression of clock genes in humans and implications for shift workers and other populations at risk.
The study of clock genes in white blood cells of human subjects in time-isolation laboratory (with Dr. Diane Boivin, Douglas Institute) allows us to ask questions on the environmental, physiological and pharmacological control of human clocks. In particular, we apply this approach to the study of shift work, and the effect of luminotherapy and pharmacological treatments.
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.
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
Silke Kiessling, Postdoc
Marc Cuesta, Postdoc (co-supervised with Dr. Diane Boivin)
Chloé Nobis, Ph.D. student
Anna Koshy, M.Sc. student (co-supervised with Dr. Diane Boivin)
In the news
Enhancing circadian clock function in cancer cells inhibits tumor growth. BMC Biol. 2017;15(1):13.
The circadian clock in immune cells controls the magnitude of Leishmania parasite infection. Sci Rep. 2017;7(1):10892.
Skin Temperature Rhythms in Humans Respond to Changes in the Timing of Sleep and Light. J Biol Rhythms. 2017;32(3):257-273.
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.
PRL2 links magnesium flux and sex-dependent circadian metabolic rhythms. JCI Insight. 2017;2(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.
Circadian clocks and inflammation: reciprocal regulation and shared mediators. Arch Immunol Ther Exp (Warsz). 2014;62(4):303-18.
A central role for ubiquitination within a circadian clock protein modification code. Front Mol Neurosci. 2014;7:69.