We’re interested in better understanding the structure, regulation and function of RNA processing complexes that are essential for life. We investigate the canonical and canonical functions of these proteins and why changes in their function(s) are linked to diseases, such as neurodevelopment and neurodegenerative disease. For example, the tRNA splicing endonuclease complex (TSEN) is essential for life and genetic mutations in the TSEN proteins are linked to a neurodevelopmental and neurodegenerative disease, Pontocerebellar Hypoplasia (PCH).

To understand what goes wrong in disease, and more broadly, understand how these proteins control cellular homeostasis, we need to better understand the “basic” functions and regulation of these proteins and their RNAs, in cells. In “healthy” cells, how are proteins regulated to make sure the proteins specifically bind to their protein partners or target their RNA substrates at the right time, place, and rate? What happens when to those RNAs when they aren’t processed efficiently? These questions require understanding how a protein behaves in a test tube (in vitro), and requires an understanding of what changes on the cellular level when the proteins do not perform their expected functions.

To understand these big picture questions, we use interdisciplinary approaches including structural biology, biochemistry and cell-based approaches. Because these proteins are essential and cannot be fully removed from cells, we also rely on disease-linked mutations to help us understand the impact disease mutations have on proteins and how these mutations impact the protein’s cellular functions (see Zavala et al, 2025, BioRxiv).

We also try to understand the structure of proteins and their interactions with RNA. By visualizing how our favorite RNA processing proteins bind to and process their RNA targets, we can better understand their cellular functions. By determining where mutations occur within proteins and protein complexes, we can formulate stronger hypotheses about the impacts of mutations, which we can then test.

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