Joseph M. Luna, PhD

RNA-binding proteins regulate nearly every step of gene expression, and for many of them we have a reasonable catalog of what they bind. What remains poorly understood is how they are organized, how their activities are coordinated across cellular compartments, and how those networks shift in response to infection, stress, or disease. The Luna Lab approaches this problem from two directions. We build tools that make these questions answerable at the resolution they require, and we deploy those tools to investigate how RBP networks are rewired in biologically consequential contexts.

On the methods side, we develop crosslinking immunoprecipitation (CLIP) approaches to capture RBP:RNA interactions with subcellular precision, resolving activity across compartments such as the nucleus, cytoplasm, stress granules, and viral replication organelles. The same RBP can have fundamentally different roles depending on where in the cell it operates, and that geography has been largely inaccessible until now. We also develop open-source computational tools to make CLIP sequencing data accessible to the broader community.

Biologically, we are drawn to RNA virus infection and intrinsic immune responses as model systems. Positive-sense RNA viruses replicate using a genome that must compete for the same RBP machinery the host uses to regulate its own transcriptome, and the host deploys that same machinery as part of its antiviral response. This makes infection a uniquely tractable context for dissecting how RBP networks are organized and what they do. A parallel line of work asks whether the molecular logic we uncover can be turned toward therapeutic ends, using programmable RNA tools to intervene in disease-relevant RNA processing.