Project 1: How do DNA viruses localize to cellular sites of DNA damage?
We are interested in understanding how viruses localize to distinct cellular sites within the host cell’s nucleus. We have adapted high throughput chromosome conformation capture-based methods to map the sites in host cells where the viral genome can localize. Using these assays, we have discovered that the parvovirus MVM has a predilection for cellular DNA damage sites, some of which are also fragile genomic regions. Our goal is to investigate the proteins at the interface between the viral and host genomes, how this changes over the course of infection and how this influences cellular DNA damage signaling over time.
Project 2: How does virus replication cause genome instability and cellular toxicity?
Viral infection of host cells induces a cellular DNA damage response (DDR) either due to the presence of foreign proteins or due to the active amplification of viral nucleic acids. This is accompanied by degradation of the cellular DNA, leading to cell cycle arrest and cell death. We are interested in understanding the molecular mechanisms deployed by invading viruses, particularly oncolytic parvoviruses, to cause cellular genome instability and ultimately cause cell death.
Project 3: Interdisciplinary application of parvovirus biology to other viral systems
We are interested in applying our findings from parvovirus research to other DNA viruses in collaboration with other investigators.