Areas of Interest
Molecular Biology of Polyomavirus-Cell Interactions
Our laboratory studies the molecular biology of the small DNA tumor virus, BK polyomavirus. BKPyV is a ubiquitous human pathogen that establishes a subclinical, persistent infection of the urinary tract during early childhood. In healthy individuals, the virus is excreted periodically into the urine but does not cause disease, but in renal and bone marrow transplant patients, the virus can cause severe and sometimes life threatening illnesses. We are interested in the interplay between viral and host factors that determine whether the virus will persist or replicate in the cell. On the host cell side, our current efforts are focused on both cytoplasmic and nuclear factors with which the virus interacts during infection. We are studying the pathway that the virus follows from the plasma membrane to the nucleus, the site of viral replication. We are also interested in control of viral replication once it reaches the nucleus. We are studying the role of a virally-encoded miRNA in regulating viral gene expression. In addition, we are investigating the genesis of viral genomic rearrangements that occur in patients with BKPyV disease, which appears to involve the cellular DNA damage response. Since there are no effective antiviral drugs with which to treat transplant patients, we are hopeful that these studies will lead to not only the discovery of important and interesting biology, but to the identification of new therapeutic targets.
Ph.D., Columbia University, 1981
Broekema, N.M. and Imperiale, M.J. (2013). miRNA regulation of BK polyomavirus replication during early infection. Proc. Natl. Acad. Sci. USA 110:8200-8205.
Bennett, S.M., Jiang, M., and Imperiale, M.J. (2013). Role of cell type-specific ER-associated degradation in polyomavirus trafficking. J. Virol. 87:8843-8852.
Casadevall, A., Enquist, L., Imperiale, M.J., Osterholm, M., Relman, D.A., and Keim, P. (2013). Redaction of sensitive data in the publication of dual use research of concern. mBio 5(1):e00991-13. doi:10.1128/mBio.00991-13.
Imperiale, M.J. (2014). Polyomavirus miRNAs: the beginning. Curr. Opin. Virol. 7:29-32.
Casadevall, A., Dermody, T.S., Imperiale, M.J., Sandri-Goldin, R.M., and Shenk, T.E. (2014). On the need for a national board to assess dual use research of concern (DURC). J. Virol. 88:6535-6537.
Casadevall A, Imperiale MJ. (2014). Risks and benefits of gain-of-function experiments with pathogens of pandemic potential, such as influenza virus: a call for a science-based discussion. mBio 5(4):e01730-14. doi:10.1128/mBio.01730-14.
Casadevall A, Howard D, Imperiale MJ. (2014). An epistemological perspective on the value of gain-of-function experiments involving pathogens with pandemic potential. mBio 5(5):e01875-14. doi:10.1128/mBio.01875-14.
Casadevall A, Howard D, Imperiale MJ. (2014). The apocalypse as a rhetorical device in the influenza virus gain-of-function debate. mBio 5(5):e02062-14. doi:10.1128/mBio.02062-14.
Imperiale, M.J. and Casadevall, A. (2014). The vagueness and costs of the pause on gain-of-function (GOF) experiments on pathogens with pandemic potential including influenza virus. mBio 5(6):e02292-14. doi:10.1128/mBio.02292-14.
Bennett, S.M., Zhao, L., Bosard, C., and Imperiale, M.J. (2015). Role of a nuclear localization signal on the minor capsid proteins VP2 and VP3 in BKPyV nuclear entry. Virology 474:110-116.
Imperiale, M.J. and Jiang, M. (2015). What DNA viral genomic rearrangements tell us about persistence. J. Virol. 89:1948-1950.
Duprex, W.P., Fouchier, R.A.M., Imperiale, M.J., Lipsitch, M., and Relman, D.A. (2015). Gain-of-function experiments: time for a real debate. Nature Rev. Microbiol. 13:58-64. doi:10.1038/nrmicro3405.
Imperiale M.J. and Casadevall, A. (2015). The importance of virology at a time of great need and great jeopardy. mBio 6(2):e00236-15.
Verhalen B., Justice, J.L., Imperiale, M.J., and Jiang, M. (2015). Viral DNA replication-dependent DNA damage response activation during BK polyomavirus infection. J. Virol. 89:5032-5039.
Imperiale, M.J. and Casadevall, A. (2015). A new synthesis for dual use research of concern. PLoS Med 12(4): e1001813. doi:10.1371/journal.pmed.1001813.
Verhaegen, M.E., Mangelberger, D., Harms, P.W., Vozheiko, T.D., Weick, J.W., Wilbert, D.M., Saunders, T.L., Ermilov, A.N., Bichakjian, C.K., Johnson, T.M., Imperiale, M.J., and Dlugosz, A.A. (2015). Merkel cell polyomavirus small T antigen is oncogenic in transgenic mice. J. Inv. Dermatol. 135, 1415–1424.
Justice, J.L., Verhalen, B., Kumar, R., Lefkowitz, E.J., Imperiale, M.J., and Jiang, M. (2015). Quantitative proteomic analysis of enriched nuclear fractions from BK polyomavirus-infected primary renal proximal tubule epithelial cells. J. Proteome Res., 14:4413-4424.
Imperiale, M.J. (2015). ASM launches mSphere. mSphere 1(1):e00006-15. doi:10.1128/mSphere.00006-15.
Imperiale, M.J. (2015). A fortuitous journey from a model system to a human pathogen. PLoS Pathog 11(12): e1005313. doi:10.1371/journal.ppat.1005313
Zhao, L., Marciano, A.T., Rivet, C.R., and Imperiale, M.J. (2016). Caveolin- and clathrin-independent entry of BKPyV into primary human proximal tubule epithelial cells. Virology 492:66-72.
Imperiale, M.J. and Casadevall, A. (2016). Zika virus focuses the gain-of-function debate. mSphere 1(2):e00069-16. doi:10.1128/mSphere.00069-16.