Research Description

I was always fascinated by the fast pace of discoveries in RNA Biology and how rapidly findings can be translated into the clinics. And after all, RNAs might have been the first molecules to form life on Earth!  Thus, I combined this interest of RNA Biology with my excitement for biochemistry to study molecular mechanism related to human health and disease.

How does RNA cleavage influence human health and disease?

Our laboratory is broadly interested in the molecular mechanisms and consequences of RNA cleavage in the cell. For instance, widespread RNA cleavage and decay is employed by both the host and viruses to promote or suppress the innate immune response. However, it remains unanswered how and why both benefit from such a widespread endonucleolytic cleavage, and many molecular mechanisms of it are unknown. 

Presence of pathogens can trigger the activation of a host endonuclease, RNase L. Activated RNase L cleaves both viral and host RNAs in single stranded regions, serving as a key component in the innate immune response. Besides this fundamental role in the response against viral infections, mutations in the RNASEL gene are associated with cancer, bacterial infections and autoimmunity. The current questions we are investigating:

1. How do RNases, such as RNase L, select their targets? How is RNase activity modulated? Can we use this knowledge to guide future therapies?

2. How does RNase activity influence physiological changes in the cell?

3. How do mutations in RNases affect outcomes of human diseases? 

To answer these questions, we apply a variety of molecular techniques including enzymology, structural biology and high-throughput sequencing (RNA-seq, ribosome profiling, Nanopore long-read sequencing) in vitro and in cell cultures.