Korennykh Lab @ Princeton

Structural & cell biology of human RNA signaling pathways

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.

Broader roles of these programs in homeostasis, cell cycle, differentiation, senescence and aging are also emerging.

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.

Our methods

X-ray crystallography
Human/murine cell biology
Systems biology