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    Maria L Zapp PhD

    TitleAssistant Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentProgram in Molecular Medicine
    AddressUniversity of Massachusetts Medical School
    373 Plantation Street
    Worcester MA 01605
    Phone508-856-4787
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentMicrobiology and Physiological Systems

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentImmunology and Virology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMolecular Genetics and Microbiology

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentCancer Center

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentCenter for AIDS Research

        Overview 
        Narrative

        Academic Background

        PhD, Baylor College of Medicine, 1989

        Regulation of retroviral and cellular mRNA transport

        Photo: Maria 
L. Zapp Studies in this laboratory focus on the regulation of gene expression at the level of RNA nucleocytoplasmic transport. As a model system for studying nuclear RNA export, we are analyzing the mechanism of action of the novel HIV-1 Rev protein. This sequence-specific RNA binding protein faciliates the redistribution of HIV-1 mRNAs that encode the viral structural protein from the nucleus to the cytoplasm. Atypical of cellular mRNAs, the gag-pol and env mRNAs leave the nucleus partially or completely unspliced. The molecular mechanism by which Rev mediates nucleocytoplasmic events remains unknown. Previous studies by several laboratories have shown that Rev function requires minimally a cis-acting sequences within the second intron of the viral pre-mRNAs, the Rev Responsive Element or "RRE" ; and a well-defined "effector" domain located at the carboxy-terminal portion of the protein. Recent studies have also identified a human nuclear-specific protein, hRIP, that interacts directly with the effector domain of Rev. The hRIP polypeptide is one possible candidate for a cellular factor that mediates Rev function. Moreover, in the absence of Rev, hRIP may play an important role in the nucleocytoplasmic transport of cellular RNAs. The identification and characterization of this cellular protein significantly enhances our ability to analyze the molecular details of Rev function and ultimately, cellular factors that mediate cellular nuclear RNA export.

        We are currently using biochemical and Xenopus laevis oocyte microinjection approaches to identify other cellular components that are required for Rev function. We have recently developed a novel in vitro nuclear RNA export assay to study cellular and viral nuclear RNA export in mammalian cells. Initially, we will use this assay system to probe Rev's mechanism of action. However, we anticipate that our in vitro nuclear RNA export assay will be a very useful tool for defining cellular factors that facilitate nuclear export of various classes of nuclear RNAs. Defining the functional role of these cellular components will provide needed insights into the molecular mechanism(s) of nuclear RNA export.



        Rotation Projects

        Rotation Projects

        • To test whether mutations in the regulatory genes enhance or block replication of the HCV replicon.

        • To test whether mutations in the regulatory genes enhance HCV cDNA replication in Huh-7 cells.

        • To identify cellular and viral factors required for replication of the HCV replicon in Huh-7 cells.



        Post Docs

        A postdoctoral position is available to study in this laboratory. Contact Dr. Zapp for additional details.

        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Xie L, Gazin C, Park SM, Zhu LJ, Debily MA, Kittler EL, Zapp ML, Lapointe D, Gobeil S, Virbasius CM, Green MR. A synthetic interaction screen identifies factors selectively required for proliferation and TERT transcription in p53-deficient human cancer cells. PLoS Genet. 2012; 8(12):e1003151.
          View in: PubMed
        2. Iben JR, Epstein JA, Bayfield MA, Bruinsma MW, Hasson S, Bacikova D, Ahmad D, Rockwell D, Kittler EL, Zapp ML, Maraia RJ. Comparative whole genome sequencing reveals phenotypic tRNA gene duplication in spontaneous Schizosaccharomyces pombe La mutants. Nucleic Acids Res. 2011 Jun; 39(11):4728-42.
          View in: PubMed
        3. Li C, Vagin VV, Lee S, Xu J, Ma S, Xi H, Seitz H, Horwich MD, Syrzycka M, Honda BM, Kittler EL, Zapp ML, Klattenhoff C, Schulz N, Theurkauf WE, Weng Z, Zamore PD. Collapse of germline piRNAs in the absence of Argonaute3 reveals somatic piRNAs in flies. Cell. 2009 May 1; 137(3):509-21.
          View in: PubMed
        4. Kahn RA, Bruford E, Inoue H, Logsdon JM, Nie Z, Premont RT, Randazzo PA, Satake M, Theibert AB, Zapp ML, Cassel D. Consensus nomenclature for the human ArfGAP domain-containing proteins. J Cell Biol. 2008 Sep 22; 182(6):1039-44.
          View in: PubMed
        5. Ghildiyal M, Seitz H, Horwich MD, Li C, Du T, Lee S, Xu J, Kittler EL, Zapp ML, Weng Z, Zamore PD. Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells. Science. 2008 May 23; 320(5879):1077-81.
          View in: PubMed
        6. Yu Z, Sánchez-Velar N, Catrina IE, Kittler EL, Udofia EB, Zapp ML. The cellular HIV-1 Rev cofactor hRIP is required for viral replication. Proc Natl Acad Sci U S A. 2005 Mar 15; 102(11):4027-32.
          View in: PubMed
        7. Sánchez-Velar N, Udofia EB, Yu Z, Zapp ML. hRIP, a cellular cofactor for Rev function, promotes release of HIV RNAs from the perinuclear region. Genes Dev. 2004 Jan 1; 18(1):23-34.
          View in: PubMed
        8. Dolganiuc A, Kodys K, Kopasz A, Marshall C, Do T, Romics L, Mandrekar P, Zapp M, Szabo G. Hepatitis C virus core and nonstructural protein 3 proteins induce pro- and anti-inflammatory cytokines and inhibit dendritic cell differentiation. J Immunol. 2003 Jun 1; 170(11):5615-24.
          View in: PubMed
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