RNA and Noncoding Mechanisms of Disease
Efforts to understand the genetic and molecular interactions contributing to the development and progression of diseases have focused mostly on protein coding genes, leaving the noncoding genome vastly under-explored. It is known that a large fraction of these noncoding regions are transcribed, generating thousands of long RNAs that do not encode proteins (lncRNAs). These lncRNAs are expressed with exquisite tissue specificity and several have been found to regulate diverse regulatory processes. Accumulating evidence also point to lncRNA loci as risk factors frequently deregulated or mutated in a wide variety of human diseases. However, whether lncRNAs contribute to the establishment or progression of diseases in vivo and how they may affect transcriptional programs and signaling pathways still remains poorly characterized. Thus, one of the main challenge to understand the noncoding genome’s influence on human health is not only to determine which lncRNAs are functional, but also to decipher how they perform their tasks and affect the pathophysiology of diseases.
The Research Unit takes advantage of human genetics data to identify lncRNAs in disease risk genomic regions. Members of the team combine genetically engineered mouse models and human cellular systems with functional genomics and CRISPR-based genome editing techniques to perturb lncRNA functions and characterize their role at a cellular and physiological level. They also aim to uncover novel noncoding RNA-based mechanisms by characterizing the molecular interactions and regulatory principles underlying the function of lncRNAs. For this, they use a combination of biochemistry, genome editing, computational and high-throughput genomics approaches to identify interacting proteins and understand how specific domains or RNA sequences within lncRNAs mediate their function.
The laboratory's goal is to better understand the impact that lncRNAs and noncoding regions have on human health and diseases and provide much needed genetics and molecular bases towards the development of novel diagnostics and RNA-targeting therapeutics.
- Director, Functional Genomics and Noncoding RNAs Research Unit, IRCM
- Assistant Research Professor, IRCM
- Assistant research professor, Department of Biochemistry and Molecular Medicine, Université de Montréal
- Member, The RNA Society
Degrees and relevant experience
- Postdoctoral fellowship, Department of Stem Cells and Regenerative Biology and the Broad Institute of MIT and Harvard, Harvard University, Cambridge, USA
- Senior Research Associate, Institute for RNA Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
- PhD in Experimental Medicine, Department de Medicine, McGill University
- BSc in Microbiology and Immunology, Department of Microbiology, Infectiology and Immunology, Université de Montréal
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Goff LA, Groff AF, Sauvageau M, Trayes-Gibson Z, Sanchez-Gomez DB, Morse M, Martin RD, Elcavage LE, Liapis SC, Gonzalez-Celeiro M, Plana O, Li E, Gerhardinger C, Tomassy GS, Arlotta P, Rinn JL, Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain. - Proceedings Of The National Academy Of Sciences Of The United States Of America 2015 Jun 2
Hacisuleyman E, Goff LA, Trapnell C, Williams A, Henao-Mejia J, Sun L, McClanahan P, Hendrickson DG, Sauvageau M, Kelley DR, Morse M, Engreitz J, Lander ES, Guttman M, Lodish HF, Flavell R, Raj A, Rinn JL, Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre. - Nature Structural & Molecular Biology 2014 Feb
Sauvageau M, Goff LA, Lodato S, Bonev B, Groff AF, Gerhardinger C, Sanchez-Gomez DB, Hacisuleyman E, Li E, Spence M, Liapis SC, Mallard W, Morse M, Swerdel MR, D'Ecclessis MF, Moore JC, Lai V, Gong G, Yancopoulos GD, Frendewey D, Kellis M, Hart RP, Valenzuela DM, Arlotta P, Rinn JL, Multiple knockout mouse models reveal lincRNAs are required for life and brain development. - ELife 2013 Dec 31
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