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Research unit director
Functional Genomics and Noncoding RNAs

We have known for a long time that RNA plays a central role in the flow of genetic information. Over the past decade, our understanding of how the genome is regulated has changed by discovering that the vast majority of noncoding regions in the genome are transcribed, generating long RNAs that don't encode proteins (lncRNAs). Thousands of lncRNA genes, expressed with exquisite tissue specificity, have been identified and several evidence indicate that they perform regulatory roles necessary for the proper functioning of our cells. lncRNAs are also frequently misregulated or mutated in a wide variety of human diseases. But, their contribution to diseases in a physiological context and their molecular mode of action remain largely unknown. Thus, one of the biggest challenge to advance our understanding of the noncoding genome’s influence on human health is not only to determine which lncRNAs are functional, but also to understand how they perform their tasks and affect the pathophysiology of diseases.

Our laboratory takes advantage of human genetic data to identify lncRNAs in disease risk genomic regions. To characterize their function and contribution to diseases, we combine genetically engineered mouse models and human cellular systems with functional genomics and CRISPR-based genome editing techniques to perturb lncRNA functions and determine their influence at a cellular and physiological level. We also aim to understand the molecular interactions and regulatory principles underlying the role of lncRNAs. For this, we use a combination of biochemistry, genome editing, computational and high-throughput genomics approaches to identify interacting proteins and specific domains or RNA sequences within lncRNAs that mediate their function.

In addition to uncovering novel noncoding RNA-based mechanisms and better understanding the impact lncRNAs and the noncoding genome have on human health and disease, this work will provide much needed genetics and molecular bases towards the development of novel diagnostics and RNA-targeting therapeutics.

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