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Department of Medicine
Department of Microbiology, Division of Infectious Diseases
Icahn School of Medicine at Mount Sinai
New York, NY
Projects and Grants
Given the ever-present global burden of emerging pathogens, the study of host-virus interactions can result in discoveries that have immediate impact on human health. We specifically focus on the interplay between RNA viruses and small RNAs. This research includes the study of miRNAs and Y-RNAs and their role, if any, in the cellular response to virus infection, the exploitation of miRNAs to control virus tropism, virus synthesis of miRNAs, and the biology of virus-derived small RNAs. Our laboratory uses several techniques to study these RNA-based host-virus interactions including genetic manipulation of both host and pathogen. We are presently working in the following areas:
- The cellular response to RNA virus infections: Following viral recognition, the cell responds with the secretion of Type I interferon (IFN-I). This is largely coordinated by cellular kinases, which mediate the activation of a number of transcription factors. These transcription factors assemble into a multisubunit complex called the enhanceosome to induce IFN-I transcription. The result of IFN-I signaling is the upregulation of a wide variety of interferon stimulated genes (ISGs) and a small subset of small RNAs (including both miRNAs and Y-RNAs). This cellular response functions to render cells resistant to viral infection. We study two kinases critical in the induction and signaling of IFN-I through the genetic manipulation of mice and subsequent in vivo virus infections.
- Exploiting microRNAs to control virus tropism: We developed a technology whereby viruses can be engineered to be susceptible to host cell miRNAs. As miRNAs can demonstrate cell- and/or species-specificity, we can use miRNA-mediated targeting to control virus tropism or the level of replication. We use this technology to address fundamental questions about immunology as well develop novel virus vaccines.
- The biology of influenza A virus small viral RNAs (svRNA): As a result of miRNA profiling in virus infected cells, we serendipitously discovered a small RNA produced by influenza A virus. While not a miRNA, this small viral RNA (svRNA) accumulates to >10000 copies per cell and has a significant impact on the virus' replicative cycle. This area of research presently focuses on the biogenesis and molecular function of svRNA.
- Non-canonical cytoplasmic production of viral miRNAs: We recently determined that viruses could be engineered to produce functional microRNAs. While this was not surprising for viruses such as influenza A virus, which replicates in the nucleus, we also found cytoplasmic viruses were capable of miRNA synthesis. This research focus is aimed at determining the molecular basis underlying this phenomenon.
Langlois, R.A., Varble, A., Chua, M.A., García-Sastre, A. and B. R. tenOever. Hematopoietic-specific targeting of influenza A virus reveals replication requirements for induction of antiviral immune response. PNAS. 2012, 109(30): 12117-22.
Backes, S., Shapiro, J.S., Sabin, L.R., Pham, A.M. Reyes, I., Moss, B., Cherry, S. and B.R. tenOever. Inactivation of host microRNAs by a viral poly(A) polymerase reveals terminal 2'-O-methylation as a protective anti-viral mechanism. Cell Host and Microbe. 2012, 12(2):200-10.
Ng, SL, Friedman, BA, Schmid, S, Gert, J, Myers, RM, tenOever, BR and T Maniatis. IKKe regulates the balance between the type I and type II interferon responses. PNAS. 2011, Dec 27; (108)(52):21170-5.
Langlois, RA, Shapiro, JS, Pham, AM and BR tenOever. in vivo delivery of cytoplasmic RNA virus-derived miRNAs. Mol. Ther. 2011, Nov 15. doi: 10.1038/mt.2011.244
Shapiro JS, Varble A, tenOever BR. Non-Canonical Cytoplasmic Processing of Viral microRNAs. RNA 2010; 16: 2068-74
Perez, J. T., A. Varble, R. Sachidanandam, I. Zlatev, M. Manoharan, A. García-Sastre, and B. R. tenOever. Influenza A Virus-Generated Small RNAs Regulate the Switch from Transcription to Replication. PNAS. 2010, 107(25):11525-30.
Varble, A., M. A. Chua, J. T. Perez, B. Manicassamy, A. García-Sastre, and B. R. tenOever. Engineered RNA viral synthesis of microRNAs. PNAS. 2010, 107(25):11519-24.
Shapiro, J.S., A. Varble, and B. R. tenOever. Non-canonical cytoplasmic processing of viral microRNAs. RNA. 2010, 16: 2068-74
Schmid, S., Mordstein, M., Kochs, G., A. García-Sastre, and B. R. tenOever. Transcription factor redundancy ensures induction of the antiviral state. JBC. 2010, 285(53): 42013-22.
Perez JT, Pham AM, Lorini MH, Chua MA, Steel J, tenOever BR. MicroRNA-mediated species-specific attenuation of influenza A virus. Nat Biotechnol 2009 Jun; 27(6): 572-576.
This information was obtained from the following websites:
The Graduate Student Research Forum is sponsored by the Graduate Student Association of the Penn State College of Medicine. The primary goal of the Forum is to promote interaction and the exchange of ideas between students and faculty. The Forum introduces students to the format generally used at scientific meetings, and it provides an opportunity to recognize excellence in graduate research at Penn State University College of Medicine.
The 2015 Forum
Patricia Opresko, PhD
|Department of Environmental and Occupational Health
University of Pittsburgh
Forum Schedule of Events
Thursday - March 5
4:00 PM - 5:00 PM Research Seminar (T2500)
Friday - March 6
8:00 AM - 8:45 AM - Breakfast/Registration (hallways outside C3621)
8:45 AM - 9:00 AM - Opening Remarks/GSA Comments (Lecture Room A)
1:45 PM - 3:15 PM - Oral Presentations 2 (Lecture Room A)
3:15 PM - 4:45 PM - Poster Presentations 2 (C3621)
6:30 PM - midnight - Forum Reception (Hershey Lodge)
Student Presenter/Faculty Evaluator Schedule