Boston University Medical Campus
Immunology Training Program

John Connor, Ph.D.

Assistant Professor of Microbiology

B.A. Swarthmore College
Ph.D. (Pharmacology) Duke University

Please also see here: www.connorlab.com

Protein synthesis is a central issue in virus replication. Though viruses absolutely need to make new proteins to replicate, they do not carry their own protein synthesis machinery. Instead, they utilize the protein synthethesis machinery of their host. My research interests are in understanding how a virus accomplishes this hostile takeover of the host machinery. I work with a prototype negative strand RNA virus, vesicular stomatitis virus (VSV) that is currently being developed as a potential antitumor agent. VSV turns off all host protein synthesis following infection, but the host protein synthesis machinery translates large amounts of viral protein. Using genetic, molecular biological, and rational mutagenesis approaches, we are investigating how VSV interacts with and dominates the host translation machinery. Our studies have shown an important role for multi-protein translation initiation complexes. Changes in the phosphorylation and makeup of these complexes correlates closely with the switch from host to viral protein synthesis. Currently the laboratory is working to determine how VSV infection is altering these complexes to favor viral translation. Our studies on VSV translation have also led us to the finding that VSV is capable of replicating under hypoxic cell stress, a difficult to treat microenvironment of solid tumors. We are currently developing new ways to use VSV as a means to target hypoxic tumor cells for destruction.

Selected recent publications

1. Pettit Kneller, E.L., Connor, J.H., and Lyles, D.S. (2009) hnRNPs relocalize to the cytoplasm following infection with vesicular stomatitis virus. J. Virol. 83:770-780.
2. Whitlow, Z.W., Connor, J.H. and Lyles, D.S. (2008) New mRNAs are preferentially translated during vesicular stomatitis virus infection. J. Virol. 82:2286-2294.
3. Connor, J.H., McKenzie, M.O., Parks, G.D., and Lyles, D.S. (2007) Antiviral activity and RNA polymerase degradation following Hsp90 inhibition in a range of negative strand viruses. Virol. 362:109-119.
4. Whitlow, Z.W., Connor, J.H., and Lyles, D.S. (2006) Preferential translation of VSV mRNAs is conferredby transcription from the viral genome. J. Virol. 80:11733-11742.
5. Hantgan R.R., Stahle M.C., Connor J.H., Horita D.A., Rocco M., McLane M.A., Yakovlev S., and Medved L. (2006) Related Integrin alphaIIbbeta3:ligand interactions are linked to binding-site remodeling. Protein Sci. 15(8):1893-1906.
6. Connor, J.H., McKenzie, M.O., and Lyles, D.S. (2006) Role of residues 121 to 124 of vesicular stomatitis virus matrix protein in virus assembly and virus-host interaction. J. Virol 80:3701-371.
7. Connor, J.H., and Lyles, D.S. (2005) Inhibition of host and viral translation during vesicular stomatitis virus infection: eIF2 is responsible for the inhibition of viral but not host translation. J. Biol. Chem. 280:13512-13519.
8. Connor, J.H., and Lyles, D.S. Inhibition of host and viral translation during vesicular stomatitis virus infection: eIF2 is responsible for the inhibition of viral but not host translation in press, JBC.
9. Connor, J.H., Naczki, C., Koumenis, C., and Lyles, D.S. (2004) Replication and cytopathic effect of oncolytic vesicular stomatitis virus in hypoxic tumor cells in vitro and in vivo. J. Virol. 78:8960-897.
10. Hantgan, R.R., Stahle, M.C., Connor, J.H., Lyles, D.S., Horita, D.A., Rocco, M., Nagaswami, C., Weisel, J.W., McLane, M.A. (2004) The disintegrin echistatin stabilizes integrin alphaIIbbeta3′s open conformation and promotes its oligomerization. J. Mol. Biol. 342:1625-163.
11. Brush, M.H., Guardiola, A., Connor, J.H., Yao, T-P., and Shenolikar, S. (2004) Protein Phosphatase-1 (PP1) complexes containing Histone Deacetylases (HDACS): Deacetylase Inhibitors Disrupt Cellular Phosphatase/HDAC Complexes. J. Biol. Chem. 279(9):7685-769.
12. Connor, J.H., and Lyles, D.H. (2002) Vesicular Stomatitis Virus Infection Alters the eIF4F Translation Initiation Complex and Causes Dephosphorylation of the eIF4E Binding Protein 4E-BP1. J.Virol. 76:10177-10187.
13. Connor, J.H., Weiser, D.C., Li, S., Hallenbeck, J., and Shenolikar, S. (2001) Growth Arrest and DNA Damage-Induced Protein, GADD34, Assembles a Novel Signaling Complex Containing Protein Phosphatase-1 and Inhibitor-1. Mol. Cell. Biol. 21: 6841-685.
14. Morishita W., Connor J.H., Xia H., Quinlan E.M., Shenolikar S., Malenka R.C. (2001) Regulation of synaptic strength by protein phosphatase 1. Neuron. 32:1133-4.
15. Shen, K., Teruel, M.N., Connor, J.H., Shenolikar, S., and Meyer, T. (2000) Molecular memory by translocation priming and postsynaptic target trapping of CaMKII. Nat. Neurosci. 3:881-88.