Benjamin R. tenOever

  • ASSOCIATE PROFESSOR Microbiology
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Education

  • Harvard University

  • Ph.D., McGill University

Biography

Awards

  • 2011 -
    Cozzarelli Prize Recipient in Biomedical Sciences
    National Academy of Science

  • 2011 -
    Investigator in the Pathogenesis of Infectious Diseases
    Burroughs Wellcome Fund

  • 2010 -
    Young Investigator Award
    American Society for Microbiology

  • 2009 -
    Milstein Young Investigator Award
    International Society of Interferon and Cytokine Research

  • 2008 -
    Pew Scholar
    Pew Charitable Trust in Biomedical Sciences

  • 2008 -
    Presidential Early Career Award for Scientists and Engineers (PECASE)
    National Science and Technology Council

Research

Specific Clinical/Research Interests: Host-Pathogen Interactions

Current Students: Alissa Pham, Jasmine Perez, Andrew Varble, Mark Chua, Jill Shapiro

Postdoctoral Fellows: Sonja Schmid, Ryan Langlois, Rohit Jangra, Simone Backes

Research Personnel: Kehinde Kassim, Ismarc Ryes

Overview:
The tenOever lab broadly focuses on the molecular interactions between viruses and their host. More specifically, the lab studies the host transcriptional response to infection and the means by which the virus circumvents these activities to propagate the infection. This research encompasses the study of cellular antiviral proteins and small RNAs, of both cellular and virus origin, which contribute to the outcome of infection. The overall objective of this lab is to gain a thorough understanding of the molecular basis of virus pathogenicity in an effort to generate improved vaccines and therapeutics.

 

Summary of Research Studies:
We 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.

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  • 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.

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  • 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.

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  • Non-canononical 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.

    • Publications

    Perez JT, Varble A, Sachidanandam R, Zlatev I, Manoharan M, Garcia-Sastre A, tenOever BR. Influenza A Virus-Generated Small RNAs Regulate the Switch from Transcription to Replication. PNAS 2010; 107(25): 11525-30.

    Varble A, Chua MA, Perez JT, Manicassamy B, Garcia-Sastre A, tenOever BR. Engineered RNA Viral Synthesis of microRNAs. PNAS 2010; 107(25): 11519-24.

    Shapiro JS, Varble A, tenOever BR. Non-Canonical Cytoplasmic Processing of Viral microRNAs. RNA 2010; 16: 2068-74.

    Schmid S, Mordstein M, Kochs G, Garcia-Sastre A, tenOever BR. 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.

    tenOever BR, Ng S, Chua M, McWhirter S, Garcia-Sastre A, Maniatis T. Multiple Functions of the IKK-related Kinase IKK-in Interferon Mediated Antiviral Immunity. Science 2007; 315: 1274-1278.

    tenOever BR, Sharma S, Grandvaux N, Zhou GP, Lin R, Hiscott J. Triggering the Interferon Antiviral Response through an IKK-related Pathway. Science 2003; 300: 1148-1151.

    Industry Relationships

    Physicians and scientists on the faculty of Mount Sinai School of Medicine often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.

    Below are financial relationships with industry reported by Dr. tenOever during 2011 and/or 2012. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

    Royalty Payments:

    • Alnylam Pharmaceuticals, Inc.

    Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://www.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.

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    Address

    Annenberg Building Floor 16 Room 16-60 (Lab)
    1468 Madison Avenue
    New York, NY 10029