Our research program focuses on elucidating the contributions of both viral and host determinants to the enhanced disease associated with highly virulent influenza viruses such as H5N1, H7N7, H7N9 and 1918 H1N1 Spanish influenza, with the ultimate goal of developing novel therapeutic options against influenza viruses and other respiratory pathogens. Some of our ongoing research projects are:

(1) Assess the importance of viral cell tropism in the pathogenesis of highly virulent influenza viruses. We engineer influenza viruses incapable of replicating in specific cell types using miRNA-mediated restriction of viral replication, and assess pathogenesis in various animal models. Our studies show that restriction of H5N1 replication from endothelial cells via highly conserved endothelial specific miR-126 completely abrogated disease symptoms in mouse and ferret models (Tundup et al, PLoS Pathogens, 2017). We are currently utilizing a combination of miRNA restricted and fluorescent reporter viruses to investigate the contribution of cell tropism to the pathogenesis of virulent influenza viruses.