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    Susan B Gagliardi PhD

    TitleProfessor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentCell and Developmental Biology
    AddressUniversity of Massachusetts Medical School
    55 Lake Avenue North
    Worcester MA 01655
    Phone508-856-2454
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentNeurology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentCell Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentNeuroscience

        Overview 
        Narrative

        Cell and Developmental Biology Department

        Academic Background

        BA., Radcliffe College, 1965
        PhD, Harvard University, 1971

        Development genetics, experimental study of myelin, cytologicaland ultrastructural methods

        The CNS myelin sheath is a specialized outgrowth of the oligodendrocyteplasma membrane which forms a multilamellar sleeve of characteristicultrastructural morphology and biochemical composition enclosing an axon. Mutations in the genes encoding the two major myelin proteins + myelinbasic protein (MBP) and proteolipid protein (PLP) + each produce specificdefects in oligodendrocyte/myelin development and morphology as well as inthe amount of the respective structural proteins. When these and/or otherCNS myelin mutations are combined in double mutant mice, we havefound that the defects in development or morphology are often alteredseparately from the protein levels. These unexpected intergenicinteractions suggest that:

        1. The wild-type MBP gene has at least two separately regulated functions.
        2. The wild-type PLP gene has at least three such independent functions.
        3. When major myelin proteins are lacking, the oligodendrocyte may makemyelin-like sheaths using other proteins + minor, transient, ornon-specific.
        4. Some function of the MBP gene may be toxic to oligodendrocytes unlessit is complemented by the proper function of the PLP gene.

         

        We are exploring and testing these ideas in our laboratories. Oneaspect of our work involves a new sex-linked lethal mouse myelin mutation(named jp4j), which we believe to be in the PLP gene. We arecurrently characterizing the mutation by sequencing the PLP gene of thejp4j mouse, studying the morphology of its oligodendrocytes andmyelin by light and electron microscopy, and determining steady-statelevels of myelin-specific mRNA’s and proteins by Northern andimmunoblots. These studies should yield important new information aboutthe relationship between location of mutations in the PLP gene andspecific impairments of gene functions. They will also be helpful inbetter understanding how PLP protein is actually integrated into themyelin membrane. Another aspect of our work involves themultidisciplinary analysis of the molecular, biochemical, and quantitativemorphological phenotypes of specific double mutant mice. Genes from whichthese combinations are being engineered include two MBP mutations, an MBPtransgene, three PLP mutations, as well as the new putative PLP mutationwhich we are characterizing. Specific phenotypes are being defined inboth the intact CNS and in the simplified environment of dispersedoligodendrocyte cultures.

        The goal of this work is to gain new insights into normal myelin geneexpression and the roles of specific proteins in CNS myelination. Thesestudies may also provide information applicable to myelin disease inhumans.



        Bibliographic 
        selected publications
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        1. Billings-Gagliardi S, Mazor KM. Effects of review on medical students' recall of different types of neuroanatomical content. Acad Med. 2009 Oct; 84(10 Suppl):S34-7.
          View in: PubMed
        2. Billings-Gagliardi S, Mazor KM. Development and validation of the stroke action test. Stroke. 2005 May; 36(5):1035-9.
          View in: PubMed
        3. Billings-Gagliardi S, Barrett SV, Mazor KM. Interpreting course evaluation results: insights from thinkaloud interviews with medical students. Med Educ. 2004 Oct; 38(10):1061-70.
          View in: PubMed
        4. Billings-Gagliardi S, Mazor KM, Belanger M. Explanations of basic medical information by students: what lay people find effective. Acad Med. 2001 Oct; 76(10 Suppl):S39-41.
          View in: PubMed
        5. Billings-Gagliardi S, Belanger M, Mazor K. A workshop for first-year medical students on communicating scientific information to patients. Acad Med. 2001 May; 76(5):531.
          View in: PubMed
        6. Billings-Gagliardi S, Nunnari JJ, Wolf MK. Rumpshaker behaves like juvenile-lethal Plp mutations when combined with shiverer in double mutant mice. Dev Neurosci. 2001; 23(1):7-16.
          View in: PubMed
        7. Wolf MK, Nunnari JN, Billings-Gagliardi S. Quaking*shiverer double-mutant mice survive for at least 100 days with no CNS myelin. Dev Neurosci. 1999; 21(6):483-90.
          View in: PubMed
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