Our lab is interested in the host pathways that determine the susceptibility of humans to viral disease. Viruses constantly evolve to exploit host machineries for their benefit whilst disarming host restriction mechanisms. Discovery of host proteins critical for viral infection illuminates basic aspects of cellular biology, reveals intricate virus host relationships, and leads to potential targets for antiviral therapeutics.
We focus on three emerging principles that are changing our understanding of virus-host interactions:
1. Genetic dissection of host factors essential for viral pathogens. Emerging and re-emerging viruses pose a constant threat to human health. Through advanced genetic screens we have identified proteins with critical roles in the replication of medically important viruses from diverse families including Ebola virus, poliovirus, dengue virus, and hepatitis C virus. We are studying the molecular details on how the viruses have hijacked these host components to facilitate their pathogenesis and are characterizing the roles they play in human biology and infectious disease.
2. Receptor discovery to improve gene therapy. Adeno-associated viruses (AAV) are non-enveloped, single-stranded DNA viruses that are non-pathogenic, lowly immunogenic and broadly tropic. These qualities make them excellent gene therapy delivery vehicles and they are lead candidates for clinical application. We have recently discovered a multi-serotype receptor for AAV (named AAVR) that is critical for AAV transduction in human cells. We are studying the role of viral receptor distribution in tissue tropism and characterizing the interaction interface between AAV and its receptor.
3. Using small molecules that target host components as novel antiviral agents. Traditionally, the development of antivirals is focused on targeting viral proteins by small molecules. Strategies that inhibit host cellular factors critical for viral infection rather than viral proteins have the potential to be more broad spectrum, more refractory to developing drug resistant mutants and provide a novel mode of action that complements direct-antiviral drugs. Thus, the identification of essential cellular factors can reveal Achilles’ heels of viral infection and provide novel antiviral drug targets.