RNA processing consists of a series of steps that are finely orchestrated by thousands of RNA Binding Proteins (RBPs) that coat transcripts upon formation. Mutations in RBPs have been directly linked to disease, implicating that RNA processing is a highly regulated process that can lead to disease when unbalanced. RNA damage has the potential to affect all these steps. There is a critical need to understand the sources and types of RNA damage, identify which RBPs are sensing and coordinating the repair of damaged transcripts, and the cellular pathways and functions affected when such interactions are dysregulated. We use cancer and stem-cell-derived neurodevelopmental models to investigate the role of damaged-RNA-RBP interactions in disease onset and treatment.
As an emerging field, there is a general lack of technologies that allow for RNA lesion detection, quantification and modification of site-specific events at a transcriptome-wide level. Furthermore, there is little understanding of specific cell-types prone to and affected by RNA damage and their correlation with disease onset, progression, and treatment. There is a clear need for methodological innovations that induce specific RNA damage to examine repair and cellular impact and measure and characterize existing RNA damage. We develop tools to detect, quantify, and modify nucleic acids and measure their repair using molecular, sequencing, and single-cell technologies.
The DNA Damage Response (DDR) machinery determines cellular fate in response to DNA damage. It then delays several cellular processes to allow for repair to occur and cell survival. If the damage is severe, it can enact in a variety of cellular outcomes, including cell death or senescence. These outcomes can directly affect disease onset, treatment, and progression in diseases such as cancer and neurodegeneration. Recent evidence suggests that RNA damage might act as an early cellular stress sensor, affecting the DDR. Moreover, proteins and enzymes historically considered DNA repair components have been recently discovered to act on RNA as well. In addition, RBPs have been shown to interact with DNA repair proteins. We investigate the crosstalk between these responses through direct and indirect regulation and interaction of its members and pathways they are involved in.