Dissecting the functions and molecular grammar of long noncoding RNAs
in development and disease.
A large fraction of mammalian genomes is transcribed, generating tens of thousands of long RNAs devoid of protein coding potential (lncRNAs). These lncRNAs are expressed with exquisite tissue specificity and several were found to regulate key cellular processes. 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 remains 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 genetically engineered animal 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. We also aim to understand the molecular grammar that underlies lncRNA function and uncover novel noncoding RNA-based mechanisms. 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 lead to the generation of novel diagnostics and therapies.
We perform functional assays to determine the role of lncRNAs in human and animal cells using a suite of genome editing, CRISPR-based systems and antisense oligos technologies.
Biochemistry & Genomics
We dissect the composition of RNA-based machines and characterize their molecular activities using state-of-the-art biochemical, molecular as well as short- and long-read sequencing-based approaches. We also work to develop novel RNA-based tools for targeted genome regulation.
Disease Modeling & RNA Therapy
We characterize the in vivo roles of lncRNAs using animal models and xenografts combined with a suite of CRISPR-based genome engineering approaches. We also actively develop novel mRNA-based and RNA-targeting therapeutics.
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