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    Last Name

    Madelyn R Schmidt PhD

    TitleResearch Associate Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentMicrobiology and Physiological Systems
    AddressUniversity of Massachusetts Medical School
    55 Lake Avenue North
    Worcester MA 01655
    Phone508-856 6040
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentImmunology and Virology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMolecular Genetics and Microbiology


        Gene therapy approaches to treat genetic immunodeficiencies

        Photo: Madelyn R. SchmidtOur laboratory is studying the mechanisms by which an RNA virus is maintained in resting B lymphocytes and how virus expression is controlled by lymphocyte activators. We have showed in in vitro studies that viral transcription, protein synthesis and replication are controlled by lymphocyte activation. We are currently examining virus persistence in lymphocytes in vivo and whether infectious virus can be reactivated after prolonged residence in B lymphocytes. These observations will be used for the development of treatments to control or clear acute and persistent infections.

        Other studies in the lab focus on determining how developing B lymphocytes enter and are maintained in the mature B cell pool in the periphery. Survival of lymphocytes from normal mice are being compared to those which carry genetic defects that alter B cell survival. Because of the need to transfer and express genes in resting primary lymphocytes in these studies, we have developed a transgenic mouse that expresses the receptor for adenovirus on lymphocytes. These transgenic mice can be readily crossed with mice that carry genetic defects so that we can use adenovirus, which efficiently infects and expresses engineered genes in resting cells, to study gene function. These studies will be used to develop new treatment modalities for use in gene therapy.

        Rotation Projects

        Potential Rotation Projects

        Project #1. Gene therapy for prostate cancer.The rotation is to produce and test adenovirus vectors that express various forms of FasL and an antisense for the metalloproteinase, MMP-7. The student will learn about cloning, the use of fluorescent reporters, the preparation and use of adenovirus stocks, and analysis of gene expression and cell populations using the fluorescence activated cell sorter and Western blotting. In vivo experiments in mice will also be carried out.

        Project #2. Analysis of mechanism of a persistent RNA virus (VSV) infection of primary lymphocytes. The rotation will involve an in vitro analysis of virus persistence in primary B cells. The student will learn preparation of primary cells, analysis of virus RNA, protein and virion production, and construct and use AdV expressing different inhibitors or activators of signaling pathways to investigate the mechanism of antibody inhibition.

        selected publications
        List All   |   Timeline
        1. Schmidt MR, McGinnes LW, Kenward SA, Willems KN, Woodland RT, Morrison TG. Long-Term and Memory Immune Responses in Mice against Newcastle Disease Virus-Like Particles Containing Respiratory Syncytial Virus Glycoprotein Ectodomains. J Virol. 2012 Nov; 86(21):11654-62.
          View in: PubMed
        2. McGinnes LW, Gravel KA, Finberg RW, Kurt-Jones EA, Massare MJ, Smith G, Schmidt MR, Morrison TG. Assembly and immunological properties of newcastle disease virus-like particles containing the respiratory syncytial virus f and g proteins. J Virol. 2011 Jan; 85(1):366-77.
          View in: PubMed
        3. Schmidt MR, Appel MC, Giassi LJ, Greiner DL, Shultz LD, Woodland RT. Human BLyS facilitates engraftment of human PBL derived B cells in immunodeficient mice. PLoS One. 2008; 3(9):e3192.
          View in: PubMed
        4. Giassi LJ, Pearson T, Shultz LD, Laning J, Biber K, Kraus M, Woda BA, Schmidt MR, Woodland RT, Rossini AA, Greiner DL. Expanded CD34+ human umbilical cord blood cells generate multiple lymphohematopoietic lineages in NOD-scid IL2rgamma(null) mice. Exp Biol Med (Maywood). 2008 Aug; 233(8):997-1012.
          View in: PubMed
        5. King M, Pearson T, Shultz LD, Leif J, Bottino R, Trucco M, Atkinson MA, Wasserfall C, Herold KC, Woodland RT, Schmidt MR, Woda BA, Thompson MJ, Rossini AA, Greiner DL. A new Hu-PBL model for the study of human islet alloreactivity based on NOD-scid mice bearing a targeted mutation in the IL-2 receptor gamma chain gene. Clin Immunol. 2008 Mar; 126(3):303-14.
          View in: PubMed
        6. Woodland RT, Fox CJ, Schmidt MR, Hammerman PS, Opferman JT, Korsmeyer SJ, Hilbert DM, Thompson CB. Multiple signaling pathways promote B lymphocyte stimulator dependent B-cell growth and survival. Blood. 2008 Jan 15; 111(2):750-60.
          View in: PubMed
        7. Woodland RT, Schmidt MR, Thompson CB. BLyS and B cell homeostasis. Semin Immunol. 2006 Oct; 18(5):318-26.
          View in: PubMed
        8. Woodland RT, Schmidt MR. Homeostatic proliferation of B cells. Semin Immunol. 2005 Jun; 17(3):209-17.
          View in: PubMed
        9. Cabatingan MS, Schmidt MR, Sen R, Woodland RT. Naive B lymphocytes undergo homeostatic proliferation in response to B cell deficit. J Immunol. 2002 Dec 15; 169(12):6795-805.
          View in: PubMed
        10. Schmidt MR, Piekos B, Cabatingan MS, Woodland RT. Expression of a human coxsackie/adenovirus receptor transgene permits adenovirus infection of primary lymphocytes. J Immunol. 2000 Oct 1; 165(7):4112-9.
          View in: PubMed
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        Office of the Vice Provost for Research, 55 Lake Ave North, Worcester, Massachusetts 01655
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