Joined the Department in 2013
- B.Sc., 1996, Sciences and Technology University of Lille (Lille, France), Molecular and Cellular Biology
- M.Sc., 1999, Louis Pasteur University (Strasbourg, France), Neurosciences
- Ph.D., 2003, Louis Pasteur University (Strasbourg, France), Neurosciences
- Postdoctoral Research, Brandeis University
Molecular Underpinnings of the Circadian Clock in Mouse
Most organisms from bacteria to humans exhibit 24-hours rhythms in their biochemistry, physiology and behavior. Best exemplified by the sleep/wake cycle, these rhythms are remarkably widespread and include in humans hormonal (e.g., melatonin, insulin, cortisol), metabolic (e.g., glucose, cholesterol), physiological and behavioral oscillations. In fact, most biological functions are rhythmic and are set to perform optimally at the most appropriate time of the day. For example, the human digestion process performs better during the day when we are supposed to eat.
These circadian rhythms are generated by “molecular clocks”, which consist of a few “clock genes” interacting in feedback loops, and which drive the rhythmic expression of a large number of genes, i.e. ~10% of the transcriptome in any tissues. This wide impact of clock genes in regulating gene expression is underscored by the surprisingly large number of pathologies developed by clock-deficient mice. In addition to being arrhythmic, these mice indeed develop pathologies as diverse as mania-like behaviors, learning and memory defects, depression, drug addiction, insomnia, metabolic diseases, arthropathy, hematopoiesis defects and cancers.
Research in our lab aims at characterizing how circadian clocks and clock genes regulate gene expression to provide insights into how and why clock dysfuntion leads to a wide spectra of pathologies. To this end, we are using a wide-range of molecular and biochemical techniques to investigate the circadian clock function at the genome-wide level (e.g., next-generation sequencing). We are currently extending some of our recent results and focus on 1) how clock genes rhythmically regulate chromatin environment and 2) the mechanisms involved in rhythmic post-transcriptional regulation of gene expression.
- Hughes, ME, Abruzzi, KC, Allada, R, Anafi, R, Arpat, AB, Asher, G et al.. Guidelines for Genome-Scale Analysis of Biological Rhythms. J. Biol. Rhythms. 2017;32 (5):380-393. doi: 10.1177/0748730417728663. PubMed PMID:29098954 .
- Lerner, I, Bartok, O, Wolfson, V, Menet, JS, Weissbein, U, Afik, S et al.. Clk post-transcriptional control denoises circadian transcription both temporally and spatially. Nat Commun. 2015;6 :7056. doi: 10.1038/ncomms8056. PubMed PMID:25952406 PubMed Central PMC4915573.
- Menet, JS, Hardin, PE. Circadian clocks: the tissue is the issue. Curr. Biol. 2014;24 (1):R25-7. doi: 10.1016/j.cub.2013.11.016. PubMed PMID:24405673 PubMed Central PMC4157344.
- Menet, JS, Pescatore, S, Rosbash, M. CLOCK:BMAL1 is a pioneer-like transcription factor. Genes Dev. 2014;28 (1):8-13. doi: 10.1101/gad.228536.113. PubMed PMID:24395244 PubMed Central PMC3894415.
- Rodriguez, J, Tang, CH, Khodor, YL, Vodala, S, Menet, JS, Rosbash, M et al.. Nascent-Seq analysis of Drosophila cycling gene expression. Proc. Natl. Acad. Sci. U.S.A. 2013;110 (4):E275-84. doi: 10.1073/pnas.1219969110. PubMed PMID:23297234 PubMed Central PMC3557077.
- Menet, JS, Rodriguez, J, Abruzzi, KC, Rosbash, M. Nascent-Seq reveals novel features of mouse circadian transcriptional regulation. Elife. 2012;1 :e00011. doi: 10.7554/eLife.00011. PubMed PMID:23150795 PubMed Central PMC3492862.
- Khodor, YL, Menet, JS, Tolan, M, Rosbash, M. Cotranscriptional splicing efficiency differs dramatically between Drosophila and mouse. RNA. 2012;18 (12):2174-86. doi: 10.1261/rna.034090.112. PubMed PMID:23097425 PubMed Central PMC3504670.
- Rodriguez, J, Menet, JS, Rosbash, M. Nascent-seq indicates widespread cotranscriptional RNA editing in Drosophila. Mol. Cell. 2012;47 (1):27-37. doi: 10.1016/j.molcel.2012.05.002. PubMed PMID:22658416 PubMed Central PMC3409466.
- Abruzzi, KC, Rodriguez, J, Menet, JS, Desrochers, J, Zadina, A, Luo, W et al.. Drosophila CLOCK target gene characterization: implications for circadian tissue-specific gene expression. Genes Dev. 2011;25 (22):2374-86. doi: 10.1101/gad.178079.111. PubMed PMID:22085964 PubMed Central PMC3222903.
- Menet, JS, Rosbash, M. A new twist on clock protein phosphorylation: a conformational change leads to protein degradation. Mol. Cell. 2011;43 (5):695-7. doi: 10.1016/j.molcel.2011.08.015. PubMed PMID:21884970 .