I study the fidelity of genome replication by viral and bacterial model systems. Why are replication enzymes so accurate? Can the mutation rates of viruses be modulated using nucleic acid analogues? We try to answer these questions by characterizing the mechanisms of DNA and RNA replication using techniques from molecular biology, X-ray crystallography, and biochemistry. I am also interested in the interactions between viruses and their receptors at the cell surface.
Miller, B.R. III, Beese, L.S., Parish, C.A., Wu, E.Y. 2015. The closing mechanism of DNA polymerase I at atomic resolution. Structure 23:1609-1620.
Miller, B.R. III, Parish, C.A., Wu, E.Y. 2014. Molecular dynamics study of the opening mechanism for DNA polymerase I. PLoS Computational Biology 10:e1003961
Wu, E.Y., Walsh, A.R., Materne, E.C., Hiltner, E.P., Zielinski, B., Miller, B.R. III, Mawby, L., Modeste, E., Parish, C.A., Barnes, W.M., Kermekchiev, M.B. 2015. A conservative isoleucine to leucine mutation causes major rearrangements and cold sensitivity in KlenTaq1 DNA polymerase. Biochemistry 54:881-9.
Wu, E.Y. and L.S. Beese. 2011. The structure of a high fidelity DNA polymerase bound to a mismatched nucleotide reveals an “ajar” intermediate conformation in the nucleotide selection mechanism. Journal of Biological Chemistry 286:19758-67.
Denby, L., L. M. Work, D. Von Seggern, E. Wu, J. H. McVey, S. A. Nicklin, A. H. Baker. 2007. Development of renal-targeted vectors through combined in vivo phage display and capsid engineering of adenoviral fibers from serotype 19p. Molecular Therapy. 15:1647-54.
Nicklin, S. A., E. Wu, G. R. Nemerow, and A. H. Baker. 2005. The influence of adenovirus fiber structure and function on vector development. Molecular Therapy. 12:384-93.
Trauger, S. A., E. Wu, S. B. Bark, G. R. Nemerow, and G. Siuzdak. 2004. Identifying viral receptors using mass spectrometry and affinity capture. ChemBioChem. 5:1095-9.
Wu, E. and G. R. Nemerow. 2004. Virus yoga: the importance of flexibility in virus host cell recognition. Trends in Microbiology. 12:162-9.
Wu, E., S. A. Trauger, L. Pache, T. Mullen, D. J. Von Seggern, G. Siuzdak, G. R. Nemerow. 2004. Membrane cofactor protein (MCP; CD46) is a receptor for adenoviruses associated with epidemic keratoconjunctivitis. Journal of Virology. 78:3897-905.
Wu, E., L. Pache, D. Von Seggern, T. Mullen, Y. Mikyas, P. L. Stewart, and G. R. Nemerow. 2003. Flexibility of the adenovirus fiber is required for efficient receptor (CAR) interaction. Journal of Virology 77:7225-7235.
Chiu, C. Y., E. Wu, S. L. Brown, D. J. Von Seggern, G. R. Nemerow, and P. L. Stewart. 2001. Structural analysis of a fiber-pseudotyped adenovirus with ocular tropism suggests differential modes of cell receptor interactions. Journal of Virology. 75:5375-80.
Wu, E., J. Fernandez, S. K. Fleck, D. J. Von Seggern, S. Huang, and G. R. Nemerow. 2001. A 50-kDa membrane protein mediates sialic acid-independent binding and infection of conjunctival cells by adenovirus type 37. Virology. 279:78-89.
Ph.D., The Scripps Research Institute