Research in the Skalsky laboratory focuses on Epstein-Barr virus, a ubiquitous herpesvirus that causes infectious mononucleosis, and is also linked to a number of cancers, particularly in immunocompromised individuals.
Using g-herpesvirus infection models (EBV and rhesus lymphocryptovirus), we aim to understand how non-coding RNAs, in particular, contribute to viral infection processes and viral oncogenesis. Current projects employ integrative approaches, including genome-wide molecular, biochemical, and bioinformatics-based strategies (i.e. CLIP-seq, next-gen sequencing, single-cell transcriptomics) to define modes of ncRNA regulation during virus infection.
Our research encompasses three focus areas:
- Roles of non-coding RNAs in anti-viral responses.
We study the interactions between viruses (namely EBV) and the RNAi machinery to identify miRNA targets and miRNA-targeted signaling pathways. Through functional in vitro studies, we have shown that multiple g-herpesvirus miRNAs disrupt pro-inflammatory cytokine signaling. We are actively pursuing additional miRNA targets, identified by high-throughput screens (i.e. PAR-CLIP, NGS), that are associated with cellular responses to virus infection.
- Molecular determinants of g-herpesvirus latency and reactivation.
We examine how post-transcriptional regulatory processes shape the EBV life cycle, specifically during cell state transitions such as the latent to lytic switch. In gain and loss of function studies, we have determined that a subset of virus-encoded small RNAs influence EBV lytic reactivation through regulation of B cell receptor signaling. Ongoing mechanistic studies are aimed at determining how viral ncRNAs participate in viral persistence in vivo.
- Co-infections and viral oncogenesis.
In collaboration with the Wong and Okoye labs at the VGTI, we examine molecular mechanisms contributing to AIDS-defining cancers in rhesus macaque models of g-herpesvirus infection. Studies include longitudinal miRNA profiling to delineate associations with viral disease progression.
Rebecca Skalsky received her bachelor’s degree from Michigan Technological University in 2002. She completed her Ph.D. in 2007 in Dr. Rolf Renne's laboratory at the University of Florida, characterizing some of the first viral miRNAs encoded by KSHV. Her post-doctoral studies were at Duke University in the laboratory of Dr. Bryan Cullen. Dr. Skalsky was awarded a K99 Career Development Award in 2014 and transferred to OHSU as an Assistant Scientist under the mentorship of Dr. Jay Nelson. She started her laboratory at the Vaccine and Gene Therapy Institute in 2016 and is currently an Assistant Professor.
Chen Y., Fachko D., Ivanov N.S., Skinner C.M., and R.L. Skalsky. Epstein-Barr virus microRNAs regulate B cell receptor signal transduction and lytic reactivation. (2019) PLoS Pathogens. 15(1):e1007535. PMCID: PMC6336353
Skinner C.M., Ivanov N.S., Barr S.A., Chen Y., and R.L. Skalsky. An Epstein-Barr Virus MicroRNA Blocks Interleukin-1 (IL-1) Signaling by Targeting IL-1 Receptor 1. (2017) J. Virol. 91(21):e00530-1. PMCID: PMC5640834
Hancock M. and R.L. Skalsky. Roles of non-coding RNAs in herpesvirus infection. (2017) Current Topics in Micro. and Immun., Springer Series. Ed: Ralph Tripp, Mark Tompkins. PMCID: PMC5754267
Skalsky RL. Analysis of Viral and Cellular MicroRNAs in EBV-Infected Cells. (2017) Methods Mol Biol.;1532:133-146. PMID:27873272
Skalsky RL, Barr SA, Jeffery AJ, Blair T, Estep R, Wong SW. Japanese Macaque Rhadinovirus Encodes a Viral MicroRNA Mimic of the miR-17 Family. (2016) J Virol. 90(20):9350-63. doi:10.1128/JVI.01123-16. PMID: 27512057
Skalsky, R.L., and B. R. Cullen. EBV noncoding RNAs, p. 181-217, Epstein Barr VirusVolume 2. Springer. (2015)
Skalsky RL, Cullen BR. EBV Noncoding RNAs. (2015) Curr Top Microbiol Immunol. 391:181-217. doi: 10.1007/978-3-319-22834-1_6. PMID:26428375
Gregorovic,G., E. A. Boulden, R. Bosshard, C. E. Karstegl, R. Skalsky, B. R. Cullen, C.Gujer, P. Rämer, C. Münz, and P. J. Farrell. Epstein-Barr viruses (EBVs) deficient in EBV-encoded RNAs have higher levels of latent membrane protein 2 RNA expression in lymphoblastoid cell lines and efficiently establish persistent infections in humanized mice. (2015) Journal of Virology 89:11711-11714.
Kang, D.,R. L. Skalsky, and B. R. Cullen. EBV BART MicroRNAs target multiplepro-apoptotic cellular genes to promote epithelial cell survival. (2015) PLoS Pathogens 11:e1004979.
Skalsky,R., and B. R. Cullen. Viruses and microRNAs in Reference Module in Biomedical Research. (2014) Elsevier Inc., 10.1016/B978-0-12-801238-3.00089-1. PMCID: PMC3621958
Skalsky RL, Olson KE, Blair CD, Garcia-Blanco MA, Cullen BR. A "microRNA-like" small RNA expressed by Dengue virus? (2014) Proc Natl Acad Sci U S A. 111(23):E2359. PMCID: PMC4060662