IRCM Researchers

Efforts to understand the genetic and molecular interactions contributing to diseases have focused mainly on the 2% of our genome that encodes proteins, leaving the rest vastly under-explored. Yet, most genetic variations associated with human disease are found in the noncoding portions of our genome. Interestingly, a large fraction of these genomic regions is transcribed, generating tens of thousands of long RNAs devoid of protein coding potential. These long noncoding RNAs (lncRNAs) are expressed with high tissue specificity, and several were found to regulate key cellular processes through largely unknown mechanisms. Evidence also points to lncRNA loci as risk factors frequently deregulated or mutated in a wide variety of human diseases. However, the extent to which lncRNAs contribute to development in vivo and how they affect transcriptional programs and signaling pathways remain poorly characterized. Thus, one of the main challenges to understand the noncoding genome’s influence on the fundamental mechanisms of life is not only to determine which lncRNAs are functional, but also decipher how they perform their tasks.
 
Our laboratory combines functional genomics, proteomics and CRISPR-based genome editing techniques to perturb lncRNA functions and characterize their role at a cellular and physiological level. We also aim to understand the molecular grammar that underlies lncRNA function and uncover novel noncoding RNA-based mechanisms to develop novel molecular tools and therapies. For this, we use a combination of biochemistry, high-throughput, and computational approaches to identify RNA-interacting macromolecules and RNA domains that mediate their function.
 
Our goal is to better understand the impact that lncRNAs and noncoding regions have on development and reveal novel RNA-based mechanisms that could be leveraged towards their use in the clinic.