Dr. Stinski's laboratory investigates human cytomegalovirus (HCMV) infection, with the goal of characterizing both the viral cis-acting elements that respond to viral and eucaryotic transcription factors and the virus-specified transcription factors. The group is addressing two broad questions with respect to HCMV biology. First, how does a virus with a strong enhancer-containing promoter-regulatory region influence expression from that promoter by viral activator and repressor proteins, and what cis elements are necessary for positive and negative regulation? Second, what are the viral transcriptional control mechanisms that determine whether an infection is persistent or latent? To answer these questions, Dr. Stinkski?s group is constructing recombinant viruses with mutated genes or regulatory elements and testing the effects of these mutations on viral replication in various cell types. Specifically, the group compares the consequences of virus infection in cells that allow for full expression of the viral genes to those of the infection in cells in which only partial expression of the viral genes occurs. The virus has been cloned into a bacterial artificial chromosome (BAC), which allows the group to generate mutations in bacteria and to test the effects of these mutations in cell culture. Research in the Stinski laboratory has been highly synergistic with vector development efforts in the Center. In this context, gene therapy related research in his laboratory has focused on applying small, highly active, promoter segments to efficient transgene expression.
Selected Publications:
Ostedgaard, T, T. Rokhlina, P. H. Karp, P. Lashmit, S. Afione, M. Schmidt, J. Zabner, M. F. Stinski, J. A. Chiorini, and M. J. Welsh. 2005. A shortened adeno-associated virus expression cassette for CFTR gene transfer to cystic fibrosis airway epithelia. Proc. Natl. Acad. Sci. 102: 2952-2957.
Petrik, D. T., K. P. Schmitt, and M. F. Stinski. 2006. Inhibition of cellular DNA synthesis by the human cytomegalovirus IE86 protein is necessary for efficient virus replication. J. Virol. 80:3872-3883.
Petrik, D. T., K. P. Schmitt, and M. F. Stinski. 2007. The autoregulatory and transactivating functions of the human cytomegalovirus IE86 protein use independent mechanisms for promoter binding. J. Virol. 81: 5807-5818.
Isomura, H., M. F. Stinski, A. Kudoh, S. Nakayama, T. Murata, Y. Sato, S. Iwahori, and T. Tsurumi. 2008. A cis element between the TATA box and the transcription start site of the major immediate-early promoter of human cytomegalovirus determines efficiency of viral replication. J. Virol. 82: 849-858.
