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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 Dec; 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 1; 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
        9. Pasquinelli AE, Ernst RK, Lund E, Grimm C, Zapp ML, Rekosh D, Hammarskjöld ML, Dahlberg JE. The constitutive transport element (CTE) of Mason-Pfizer monkey virus (MPMV) accesses a cellular mRNA export pathway. EMBO J. 1997 Dec 15; 16(24):7500-10.
          View in: PubMed
        10. Zapp ML, Young DW, Kumar A, Singh R, Boykin DW, Wilson WD, Green MR. Modulation of the Rev-RRE interaction by aromatic heterocyclic compounds. Bioorg Med Chem. 1997 Jun; 5(6):1149-55.
          View in: PubMed
        11. Ratmeyer L, Zapp ML, Green MR, Vinayak R, Kumar A, Boykin DW, Wilson WD. Inhibition of HIV-1 Rev-RRE interaction by diphenylfuran derivatives. Biochemistry. 1996 Oct 22; 35(42):13689-96.
          View in: PubMed
        12. Zhang G, Zapp ML, Yan G, Green MR. Localization of HIV-1 RNA in mammalian nuclei. J Cell Biol. 1996 Oct; 135(1):9-18.
          View in: PubMed
        13. Werstuck G, Zapp ML, Green MR. A non-canonical base pair within the human immunodeficiency virus rev-responsive element is involved in both rev and small molecule recognition. Chem Biol. 1996 Feb; 3(2):129-37.
          View in: PubMed
        14. Symensma TL, Giver L, Zapp M, Takle GB, Ellington AD. RNA aptamers selected to bind human immunodeficiency virus type 1 Rev in vitro are Rev responsive in vivo. J Virol. 1996 Jan; 70(1):179-87.
          View in: PubMed
        15. Fritz CC, Zapp ML, Green MR. A human nucleoporin-like protein that specifically interacts with HIV Rev. Nature. 1995 Aug 10; 376(6540):530-3.
          View in: PubMed
        16. Zapp ML. The ins and outs of RNA nucleocytoplasmic transport. Curr Opin Genet Dev. 1995 Apr; 5(2):229-33.
          View in: PubMed
        17. Somasundaran M, Zapp ML, Beattie LK, Pang L, Byron KS, Bassell GJ, Sullivan JL, Singer RH. Localization of HIV RNA in mitochondria of infected cells: potential role in cytopathogenicity. J Cell Biol. 1994 Sep; 126(6):1353-60.
          View in: PubMed
        18. Giver L, Bartel DP, Zapp ML, Green MR, Ellington AD. Selection and design of high-affinity RNA ligands for HIV-1 Rev. Gene. 1993 Dec 27; 137(1):19-24.
          View in: PubMed
        19. Giver L, Bartel D, Zapp M, Pawul A, Green M, Ellington AD. Selective optimization of the Rev-binding element of HIV-1. Nucleic Acids Res. 1993 Nov 25; 21(23):5509-16.
          View in: PubMed
        20. Zapp ML, Stern S, Green MR. Small molecules that selectively block RNA binding of HIV-1 Rev protein inhibit Rev function and viral production. Cell. 1993 Sep 24; 74(6):969-78.
          View in: PubMed
        21. Zapp ML. RNA nucleocytoplasmic transport. Semin Cell Biol. 1992 Aug; 3(4):289-97.
          View in: PubMed
        22. Bartel DP, Zapp ML, Green MR, Szostak JW. HIV-1 Rev regulation involves recognition of non-Watson-Crick base pairs in viral RNA. Cell. 1991 Nov 1; 67(3):529-36.
          View in: PubMed
        23. Zapp ML, Hope TJ, Parslow TG, Green MR. Oligomerization and RNA binding domains of the type 1 human immunodeficiency virus Rev protein: a dual function for an arginine-rich binding motif. Proc Natl Acad Sci U S A. 1991 Sep 1; 88(17):7734-8.
          View in: PubMed
        24. Zamore PD, Zapp ML, Green MR. Gene expression. RNA binding: beta s and basics. Nature. 1990 Dec 6; 348(6301):485-6.
          View in: PubMed
        25. Southgate C, Zapp ML, Green MR. Activation of transcription by HIV-1 Tat protein tethered to nascent RNA through another protein. Nature. 1990 Jun 14; 345(6276):640-2.
          View in: PubMed
        26. Zapp ML, Green MR. Sequence-specific RNA binding by the HIV-1 Rev protein. Nature. 1989 Dec 7; 342(6250):714-6.
          View in: PubMed
        27. Green MR, Zapp ML. Human immunodeficiency virus. Revving up gene expression. Nature. 1989 Mar 16; 338(6212):200-1.
          View in: PubMed
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