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Senior Advisor to the President
Former W.W. Smith Chair in Cancer Research
Work in the Skalka laboratory has been focused on obtaining a detailed understanding of the mechanism by which retroviral DNA is integrated into its host cell chromatin, and discovering the epigenetic factors and processes that affect its subsequent expression. Retroviruses are of special interest, not only because they are agents of disease, including cancer, but also because they are important as vehicles for the insertion of desired genes into target cells for scientific investigation and gene therapy.
A broad range of investigational methods have been exploited in these studies from analyses of protein function, to in vivo studies of viral growth and cell biology. Our overarching goals have been to uncover new information of fundamental importance to both virus and cell biology, and to identify new targets for therapies to treat disease.
Skalka, A.M. Retroviral DNA transposition: Themes and variations. In: Mobile DNA III (Sandmeyer, S., Craig, N., eds.). ASM Press, in press, 2015. Available in Microbiology http://www.asmscience.org/content/journal/microbiolspec/2/5
Benleulmi, M.S., Matysiak, J., Henriquez, D.R., Vaillant, C., Lesbats, P., Calmels, C., Naughtin, M., Leon, O., Skalka, A.M., Ruff, M., Lavigne, M., Andreola, M.L., Parissi, V. Intasome architecture and chromatin density modulate retroviral integration into nucleosome. Retrovirology 12:13-29, 2015. PMCID: PMC4358916 http://www.ncbi.nlm.nih.gov/pubmed/25807893
Haugh, K.A., Shalginskikh, N., Nogusa, S., Skalka, A.M., Katz, R.A., Balachandran, S. The interferon-inducible antiviral protein Daxx is not essential for interferon-mediated protection against avian sarcoma virus. Virol. J. 11:100, 2014. PMCID: PMC4049388 http://www.ncbi.nlm.nih.gov/pubmed/24884573
Poleshko, A., Kossenkov, A.V., Shalginskikh, N., Pecherskaya, A., Einarson, M.B., Skalka, A.M., Katz, R.A. Human factors and pathways essential for mediating epigenetic gene silencing. Epigenetics 9:1280-1289, 2014. PMCID: PMC4169020 http://www.ncbi.nlm.nih.gov/pubmed/25147916
Bojja, R.S., Andrake, M.D., Merkel, G., Weigand, S., Dunbrack, R.L., Jr., Skalka, A.M. Architecture and assembly of HIV integrase multimers in the absence of DNA substrates. J. Biol. Chem. 288:7373-7386, 2013. PMCID: PMC3591645 http://www.ncbi.nlm.nih.gov/pubmed/23322775
Shalginskikh, N., Poleshko, A., Skalka, A.M., Katz, R.A. Retroviral DNA methylation and epigenetic repression are mediated by the antiviral host protein Daxx. Selected by the Editors as an Article of "Significant Interest". J. Virol. 87:2137-2150, 2013. PMCID: PMC3571491 http://www.ncbi.nlm.nih.gov/pubmed/23221555
Peletskaya, E., Andrake, M., Gustchina, A., Merkel, G., Alexandratos, J., Zhou, D., Bojja, R.S., Satoh, T., Potapov, M., Kogon, A., Potapov, V., Wlodawer, A., Skalka, A.M. Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis. PLoS One 6:e27751, 2011. PMCID: PMC3228729 http://www.ncbi.nlm.nih.gov/pubmed/22145019
Katz, R.A., Merkel, G., Andrake, M.D., Roder, H., Skalka, A.M. Retroviral integrases promote fraying of viral DNA ends. J. Biol. Chem. 286:25710-25718, 2011. PMCID: PMC3138259 http://www.ncbi.nlm.nih.gov/pubmed/21622554
Bojja, R.S., Andrake, M.D., Weigand, S., Merkel, G., Yarychkivska, O., Henderson, A., Kummerling, M., Skalka, A.M. Architecture of a full-length retroviral integrase monomer and dimer, revealed by small angle X-ray scattering and chemical cross-linking. J. Biol. Chem. 286:17047-17059, 2011. PMCID: PMC3089549 http://www.ncbi.nlm.nih.gov/pubmed/21454648
Belyi, V.A., Levine, A.J., Skalka, A.M. Sequences from ancestral single-stranded DNA viruses in vertebrate genomes: the parvoviridae and circoviridae are more than 40 to 50 million years old. J. Virol. 84:12458-12462, 2010. PMCID: PMC297638 http://www.ncbi.nlm.nih.gov/pubmed/20861255
Belyi, V.A., Levine, A.J., Skalka, A.M. Unexpected inheritance: multiple integrations of ancient bornavirus and ebolavirus/marburgvirus sequences in vertebrate genomes. PLoS Pathog. 6:e1001030, 2010. PMCID: PMC2912400 http://www.ncbi.nlm.nih.gov/pubmed/20686665
Poleshko, A., Einarson, M.B., Shalginskikh, N., Zhang, R., Adams, P.D., Skalka, A.M., Katz, R.A. Identification of a functional network of human epigenetic silencing factors. J. Biol. Chem. 285:422-433, 2010. PMCID: PMC2804189 http://www.ncbi.nlm.nih.gov/pubmed/19880521
Andrake, M.D., Ramcharan, J., Merkel, G., Zhao, X.Z., Burke, T.R., Jr., Skalka, A.M. Comparison of metal-dependent catalysis by HIV-1 and ASV integrase proteins using a new and rapid, moderate throughput assay for joining activity in solution. AIDS Res. Ther. 6:14, 2009. PMCID: PMC2717984 http://www.ncbi.nlm.nih.gov/pubmed/19563676
Merkel, G., Andrake, M.D., Ramcharan, J., Skalka, A.M. Oligonucleotide-based assays for integrase activity. Methods 47:243-248, 2009. PMCID: PMC2743288 http://www.ncbi.nlm.nih.gov/pubmed/19010419
Andrake, M.D., Sauter, M.M., Boland, K., Goldstein, A.D., Hussein, M., Skalka, A.M. Nuclear import of Avian Sarcoma Virus integrase is facilitated by host cell factors. Retrovirology 5:73, 2008. PMCID: PMC2527327 http://www.ncbi.nlm.nih.gov/pubmed/18687138
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