Malathi Krishnamurthy, PhD

Research in the Krishnamurthy lab focuses on host response during viral infections. Our studies address the fundamental mechanisms by which cells resist infection and how cells know they are infected by a virus. The innate immune pathway is the first line of defense against viruses and functions to limit viral replication and spread. Pattern-Recognition Receptors including Rig-I-like helicases (Rig-I and MDA5) and Toll-like receptors (TLRs) recognize conserved microbial features (Pathogen associated Molecular Pattern, PAMP) and provide signals to initiate immune response by producing type I IFN and cytokines. Double stranded RNA produced during viral infections serves as PAMP and activates the IFN-inducible 2’,5’ - oligoadenylate synthetase (OAS) which converts cellular ATP to unique 2’,5’ - linked oligoadenylates, 2-5A, which binds and activates a ubiquitous and latent endoribonuclease, RNase L. Activated RNase L cleaves single stranded viral and host RNAs to produce small RNAs with duplex  structures which can signal through Rig-I and MDA5 to amplify the production of IFN-β. Studies in the lab are aimed at investigating the signaling pathway initiated by small RNA cleavage products of RNase L and the expanding roles of RNase L in innate immunity.

 

Areas of research in our group include:

1. Regulation of autophagy and cell death pathways

2. Non-enzymatic antiviral role of RNase L

3. Role of small cellular RNAs generated by RNaseL in innate immunity

4. RNase L-Filamin A interaction in prostate cancer