Faculty

Christopher  Sullivan

Sullivan, Christopher
Associate Professor in Molecular Genetics and Microbiology

E-mail

Website

Main Office: NMS 3.110
Phone: (512) 471-5391

Alternate Office: NMS 3.212
Phone: (512) 471-4648

Mailing Address:
The University of Texas at Austin
Molecular Genetics & Microbiology
2506 Speedway Stop A5000
Austin, TX 78712-1191


Research Lab Students:
    Graduate Student
  • Burke, James - Graduate Student
  • Chen, Chun-Jung - Graduate Student
  • Cox, Jennifer - Graduate Student
  • Kincaid, Rodney - Graduate Student


  • Research Summary:

    The discovery of RNA interference (RNAi) and small regulatory RNAs such as siRNAs and miRNAs, has dramatically changed our understanding of the regulation of gene expression. Consequently, RNAi has generated much excitement due to its regulatory and therapeutic potential. Our research focuses on understanding the interaction of viruses with the RNAi machinery in mammalian cells. We have shown that members of different tumor virus families (including Polyomaviridae, Herpesviridae, and Retroviridae) encode microRNAs; likely to aid in their own replication and to promote infectivity. Members of the Polyoma virus family induce tumors in model organisms and at least one member (MCV) is associated with human tumors. Kaposi's Sarcoma associated Herpes Virus (KSHV) promotes highly vascularized skin lesions and rare B cell lymphomas, predominantly in immunosuppresed AIDS patients. Our goals are several-fold: (1) to understand the functions of viral and host encoded microRNAs and how they contribute to viral lifecycle, pathogenesis and tumorigenesis, (2) to identify novel interactions of mammalian viruses with the host RNAi machinery, (3) to uncover new mechanisms of gene regulation utilized by tumor viruses and the host in response to infection, and (4) to use viruses as "molecular divining rods" to probe for new classes of host defense pathways.

    Research Images:

    Nodamura virus protein B2 is localized to cytoplasm - B2 is a viral protein that inhibits RNA interference (RNAi) in mamallian cells. Its cytoplasmic localization allows it to bind to RNAs that correspond to substrates and products of Dicer, a key enzyme in the RNAi pathway.

    Microrarray analysis identifies viral microRNAs - Using a novel approach that integrates microarray analysis with computational prediction we have identified over 20 new microRNAs encoded by several different DNA tumor viruses.

    KSHV encodes "antisense" miRNAs - Using a unique approach to enrich for bona fide miRNAs amidst a high background of RNA degradation fragments that are common during lytic viral infection, we have shown that KSHV encodes miRNAs antisense to the known KSHV miRNAs. Due to their low abundance, it is unknown if these AS miRNAs are biologically relevant, however, this work clearly shows that KSHV encodes transcripts complementary to viral miRNAs. This add KSHV to a growing list of viruses that encode miRNAs complementary to noncoding RNAs and opens up the possibility of novel functions for KSHV miRNAs.

     
    Publications:
    2013G. J. Seo, R. P. Kincaid, T. Phanaksri, J. M. Burke, J. M. Pare, J. E. Cox, T. Y. Hsiang, R. M. Krug, C. Sullivan., Reciprocal inhibition between intracellular antiviral signaling and the RNAi machinery in mammalian cells., Cell Host Microbe In press.
    2013L. V. McClure, R. P. Kincaid, J. M. Burke, A. Grundhoff, and C. S. Sullivan., Comprehensive mapping and analysis of KSHV 3UTRs identifies differential post-transcriptional control of gene expression in lytic versus latent infection., J. Virol. In press.
    2013C. J. Chen, J. E. Cox, R. P. Kincaid, A. Martinez, and C. S. Sullivan., Divergent microRNA targetomes of closely related circulating strains of polyomavirus., J. Virol. In press.
    2012R. P. Kincaid, and C. S. Sullivan., Virus- encoded microRNAs: An overview and a look to the future., PLoS Pathogens. 8(12):.
    2012Kincaid RP, Burke JM, Sullivan CS, RNA virus microRNA that mimics a B-cell oncomiR, PNAS 109(8): In press.
    2011YT Lin and Sullivan CS, Expanding the Role of Drosha to the Regulation of Viral Gene Expression, PNAS 108(27):11229-34.
    2011Chen CJ, Kincaid RP, Seo GJ, Bennett MD, Sullivan CS, Insights into Polyomaviridae microRNA function derived from the study of the bandicoot papillomatosis carcinomatosis viruses., J Virol 85(9):4487-500.
    2010Lin YT, Kincaid RP, Arasappan D, Dowd SE, Hunicke-Smith SP, Sullivan CS., Small RNA profiling reveals antisense transcription throughout the KSHV genome and novel small RNAs, RNA 16(8):1540-58.
    2009Ziegelbauer JM, Sullivan CS, Ganem D., Tandem array-based expression screens identify host mRNA targets of virus-encoded microRNAs, Nat Genet 141:130-4.
    2009Seo GJ, Chen CJ, Sullivan CS., Merkel cell polyomavirus encodes a microRNA with the ability to autoregulate viral gene expression, Virology 383:183-7 .
    2008McClure LV, Sullivan CS., Kaposi's sarcoma herpes virus taps into a host microRNA regulatory network, Cell Host Microbe 3:1-3.
    2008Sullivan CS, New roles for large and small viral RNAs in evading host defences, Nat Rev Genet 9:503-7.
    2008Seo GJ, Fink LH, O'Hara B, Atwood WJ, Sullivan CS., Evolutionarily conserved function of a viral microRNA, J Virol 82:9823-8 .
    2005CS Sullivan and Ganem D, A virus-encoded inhibitor that blocks RNA interference in mammalian cells, J. Virol 79:7371-9.
    2005CS Sullivan, Grundhoff AT, Tevethia S, Pipas JM, Ganem D, SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells, Nature 435:682-6.

     
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