Research Summary

Our lab uses a combination of computational and experimental techniques to study RNA-binding proteins (RBPs). On the high-throughput scale, we use RNA Bind-n-Seq (RBNS) to study RBP affinity to millions of diverse RNA sequences for dozens of RBPs. A major research area in the lab, then, is to characterize the many complex and non-canonical determinants of RNA-binding protein binding, including those that prefer certain RNA structures, bipartite binding patterns, or specific local sequence contexts. Ultimately, we want to understand how these specificities create dynamism in the regulation of RNA alternative splicing and gene expression. To this end, we construct quantitative, biophysical models for these interactions as well as evaluate them in the context of the cell using a variety of methods and data.

Another research area in the lab is to elucidate the mechanisms and implications of RNA splicing. We currently have several projects investigating the relationship among splicing, transcription, and gene expression by probing phenomena such as intron-mediated enhancement (IME) of gene expression. We are also building probabilistic models of splicing to better understand alternative splicing and spliceosome dynamics. These efforts altogether aim to uncover the molecular connections between different layers of RNA regulation.

In all of our work, we use biochemical and molecular observations to ultimately take a genome-wide perspective with an eye toward human variation, disease, and the evolution of gene regulation.