We aim to understand mechanisms of human innate immunity, response to damage, and stress. In particular, we are interested in structural and cell biology of pathways mediated by dsRNA, other kinds of RNA, and by receptor proteins that recognize or process these RNA molecules.
Intracellular response to dsRNA
Double-stranded RNA or dsRNA is a major regulator of gene expression in all mammalian cells. A number of membrane-tethered, cytosolic and nuclear proteins serve as receptors that recognize dsRNA and control dsRNA response. Often, dsRNA response is linked to the production of interferons, pro-inflammatory cytokines and control of innate and adaptive immunity.
Other signaling RNA
One of the key programs activated by dsRNA in all mammalian cells involves cleavage of the intracellular RNA pool by a kinase family receptor, RNase L. We are interested in structural and cell biology of RNase L.
We are also interested in a sister protein of RNase L, Ire1. Ire1 controls the unfolded protein response (UPR) by splicing an intron from a transcription factor XBP1 mRNA -- without using the spliceosome. As we have shown recently, Ire1 and RNase L employ similar mechanisms for RNA recognition.
Human/murine cell biology