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    Jeanne B Lawrence PhD

    TitleChair and Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentCell and Developmental Biology
    AddressUniversity of Massachusetts Medical School
    55 Lake Avenue North
    Worcester MA 01655
    Phone508-856-6015
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentPediatrics

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentCell Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMD/PhD Program

        Overview 
        Narrative

        CDB Department Website

        Lawrence Lab Website

        Academic Background

        1977-1982Brown University, Providence, Rhode Island
        Program in Molecular and Cell Biology
        Degree: Ph.D.
        Discipline: Developmental Biology

        1974-1975Rutgers University, New Brunswick, New Jersey
        Degree: M.S.
        Discipline: Human Genetics and Genetic Counseling

        1971-1973Stephens College, Columbia, Missouri
        Degree: B.A., Summa Cum Laude
        Double Major: Biology and Music

        1969-197lSimmons College
        Boston, Massachusetts

        Genome Organization and the Functional Relationship of DNA/RNA with Nuclear Structure

        Research Interests

        Jeanne Lawrence’s research bridges fundamental questions about genome regulation with pursuing the clinical implications of recent advances in the studies of epigenetics. The genome is not a linear entity, but exists as a complex three-dimensional configuration within a highly complex nuclear structure. A major focus of Jeanne’s lab has been to demonstrate and investigate the functional organization of specific human genes and their cognate mRNAs within a highly compartmentalized nuclear structure. In recent years it has become increasingly well appreciated that the nucleus contains a number of non-chromatin “compartments”, enriched in different subsets of RNA metabolic factors. The Lawrence Lab has demonstrated that there is a locus-specific organization of genomic DNA with respect to distinct nuclear compartments, which relates and contributes to gene regulation. Some nuclear structures or bodies, including the specific heterochromatic structures, are involved in genetic diseases. Examples studied in the Lawrence Lab include toxic repeat nuclear RNA foci in myotonic dystrophy or epigenetic defects of heterochromatin in FSH muscular dystrophy. Most recently Jeanne’s work has come to focus most heavily on epigenetic changes to nuclear structure and heterochromatin in human pluripotent stem cells (iPS cells) and in cancer cells or tumors.

        A pre-eminent model for early embryonic regulation by heterochromatin formation is the inactivation of the human X-chromosome, where epigenetic changes are manifest cytologically across an entire chromosome. The Lawrence Lab is at the forefront of investigating how a large non-coding RNA can control this whole process. The XIST gene was identified in other labs as a potential key to the X-inactivation process, however the RNA did not encode an open-reading frame. Using powerful molecular cytology approaches developed in the Lawrence Lab, we were able to demonstrate that the XIST gene produced a stable, functional nuclear RNA that actually “paints” the entire inactive X-chromosome, but not the active X chromosome. Spreading of XIST RNA across the chromosome is the first step in transforming it into a heterochromatic state. This established the precedent for a new type of functional nuclear RNA involved in chromatin regulation, and other large non-coding RNAs are also being examined in the Lawrence Lab. Current studies focus on how XIST RNA interacts with the chromosome, and what DNA sequences and chromosomal proteins impact this process, using XIST transgenics and bioinformatics as well as cytological epigenetics. Currently, the Lawrence Lab is also pursuing a novel translational approach for gene therapy that stems from these advances in understanding non-coding RNA and chromosome regulation.

        Course Information

        In addition to her research, Jeanne B. Lawrence Ph.D.,is also the co-director of the Human Genetics Course at UMass Medical School ,which focuses on the genetic knowledge and concepts which underlies almost every aspect of human health, both in normal function and disease. The course covers chromosomal, single gene, and multifactorial disorders, including quantitative analysis of Mendelian and non-Mendelian inheritance, human cancer genetics, epigenomic regulation and recent developments in human genome research.

        Figure

        Lawrence Nucleus Figure



        Rotation Projects

        Potential Rotation Projects

        1. Very recently we have discovered evidence for a novel intranuclear body marked by an oncogenic protein mutated in many cancers. A high priority will now be to examine the relationship of this novel structure to growth control in normal and cancer cells, and its dynamic interactions with other know nuclear bodies and regulation of specific genes. Another project on nuclear compartments investigates the impact of triplet repeat mutations on expression, processing and transport of specific RNAs in human genetic diseases, such as myotonic dystrophy.


        2. Recent studies indicate that there is sequence specificity in the relationship of XIST RNA to the chromosome. The role of XIST RNA in X-inactivation is being examined using transgenes in ES cells, and the sequence specificity is being approached using bioinformatic analysis of genomic sequence.


        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Hall LL, Carone DM, Gomez AV, Kolpa HJ, Byron M, Mehta N, Fackelmayer FO, Lawrence JB. Stable C0T-1 repeat RNA is abundant and is associated with euchromatic interphase chromosomes. Cell. 2014 Feb 27; 156(5):907-19.
          View in: PubMed
        2. Swanson EC, Manning B, Zhang H, Lawrence JB. Higher-order unfolding of satellite heterochromatin is a consistent and early event in cell senescence. J Cell Biol. 2013 Dec 23; 203(6):929-42.
          View in: PubMed
        3. Lawrence J. Interview: from Down's syndrome to basic epigenetics and back again. Epigenomics. 2013 Dec; 5(6):611-4.
          View in: PubMed
        4. Carpenter S, Aiello D, Atianand MK, Ricci EP, Gandhi P, Hall LL, Byron M, Monks B, Henry-Bezy M, Lawrence JB, O'Neill LA, Moore MJ, Caffrey DR, Fitzgerald KA. A long noncoding RNA mediates both activation and repression of immune response genes. Science. 2013 Aug 16; 341(6147):789-92.
          View in: PubMed
        5. Jiang J, Jing Y, Cost GJ, Chiang JC, Kolpa HJ, Cotton AM, Carone DM, Carone BR, Shivak DA, Guschin DY, Pearl JR, Rebar EJ, Byron M, Gregory PD, Brown CJ, Urnov FD, Hall LL, Lawrence JB. Translating dosage compensation to trisomy 21. Nature. 2013 Aug 15; 500(7462):296-300.
          View in: PubMed
        6. Byron M, Hall LL, Lawrence JB. A Multifaceted FISH Approach to Study Endogenous RNAs and DNAs in Native Nuclear and Cell Structures. Curr Protoc Hum Genet. 2013 Jan; Chapter 4:Unit4.15.
          View in: PubMed
        7. Carone DM, Lawrence JB. Heterochromatin instability in cancer: From the Barr body to satellites and the nuclear periphery. Semin Cancer Biol. 2013 Apr; 23(2):99-108.
          View in: PubMed
        8. Jiao B, Ma H, Shokhirev MN, Drung A, Yang Q, Shin J, Lu S, Byron M, Kalantry S, Mercurio AM, Lawrence JB, Hoffmann A, Bach I. Paternal RLIM/Rnf12 Is a Survival Factor for Milk-Producing Alveolar Cells. Cell. 2012 Apr 27; 149(3):630-41.
          View in: PubMed
        9. Shin J, Bossenz M, Chung Y, Ma H, Byron M, Taniguchi-Ishigaki N, Zhu X, Jiao B, Hall LL, Green MR, Jones SN, Hermans-Borgmeyer I, Lawrence JB, Bach I. Maternal Rnf12/RLIM is required for imprinted X-chromosome inactivation in mice. Nature. 2010 Oct 21; 467(7318):977-81.
          View in: PubMed
        10. Hall LL, Byron M, Pageau G, Lawrence JB. AURKB-mediated effects on chromatin regulate binding versus release of XIST RNA to the inactive chromosome. J Cell Biol. 2009 Aug 24; 186(4):491-507.
          View in: PubMed
        11. Butler JT, Hall LL, Smith KP, Lawrence JB. Changing nuclear landscape and unique PML structures during early epigenetic transitions of human embryonic stem cells. J Cell Biochem. 2009 Jul 1; 107(4):609-21.
          View in: PubMed
        12. Clemson CM, Hutchinson JN, Sara SA, Ensminger AW, Fox AH, Chess A, Lawrence JB. An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol Cell. 2009 Mar 27; 33(6):717-26.
          View in: PubMed
        13. Lawrence JB, Clemson CM. Gene associations: true romance or chance meeting in a nuclear neighborhood? J Cell Biol. 2008 Sep 22; 182(6):1035-8.
          View in: PubMed
        14. Hall LL, Byron M, Butler J, Becker KA, Nelson A, Amit M, Itskovitz-Eldor J, Stein J, Stein G, Ware C, Lawrence JB. X-inactivation reveals epigenetic anomalies in most hESC but identifies sublines that initiate as expected. J Cell Physiol. 2008 Aug; 216(2):445-52.
          View in: PubMed
        15. Mudhasani R, Zhu Z, Hutvagner G, Eischen CM, Lyle S, Hall LL, Lawrence JB, Imbalzano AN, Jones SN. Loss of miRNA biogenesis induces p19Arf-p53 signaling and senescence in primary cells. J Cell Biol. 2008 Jun 30; 181(7):1055-63.
          View in: PubMed
        16. Smith KP, Byron M, Johnson C, Xing Y, Lawrence JB. Defining early steps in mRNA transport: mutant mRNA in myotonic dystrophy type I is blocked at entry into SC-35 domains. J Cell Biol. 2007 Sep 10; 178(6):951-64.
          View in: PubMed
        17. Pageau GJ, Hall LL, Ganesan S, Livingston DM, Lawrence JB. The disappearing Barr body in breast and ovarian cancers. Nat Rev Cancer. 2007 Aug; 7(8):628-33.
          View in: PubMed
        18. Pageau GJ, Hall LL, Lawrence JB. BRCA1 does not paint the inactive X to localize XIST RNA but may contribute to broad changes in cancer that impact XIST and Xi heterochromatin. J Cell Biochem. 2007 Mar 1; 100(4):835-50.
          View in: PubMed
        19. Pageau GJ, Lawrence JB. BRCA1 foci in normal S-phase nuclei are linked to interphase centromeres and replication of pericentric heterochromatin. J Cell Biol. 2006 Dec 4; 175(5):693-701.
          View in: PubMed
        20. Hall LL, Smith KP, Byron M, Lawrence JB. Molecular anatomy of a speckle. Anat Rec A Discov Mol Cell Evol Biol. 2006 Jul; 288(7):664-75.
          View in: PubMed
        21. Clemson CM, Hall LL, Byron M, McNeil J, Lawrence JB. The X chromosome is organized into a gene-rich outer rim and an internal core containing silenced nongenic sequences. Proc Natl Acad Sci U S A. 2006 May 16; 103(20):7688-93.
          View in: PubMed
        22. McNeil JA, Smith KP, Hall LL, Lawrence JB. Word frequency analysis reveals enrichment of dinucleotide repeats on the human X chromosome and [GATA]n in the X escape region. Genome Res. 2006 Apr; 16(4):477-84.
          View in: PubMed
        23. Smith KP, Byron M, O'Connell BC, Tam R, Schorl C, Guney I, Hall LL, Agrawal P, Sedivy JM, Lawrence JB. c-Myc localization within the nucleus: evidence for association with the PML nuclear body. J Cell Biochem. 2004 Dec 15; 93(6):1282-96.
          View in: PubMed
        24. Smith KP, Byron M, Clemson CM, Lawrence JB. Ubiquitinated proteins including uH2A on the human and mouse inactive X chromosome: enrichment in gene rich bands. Chromosoma. 2004 Dec; 113(6):324-35.
          View in: PubMed
        25. Tam R, Smith KP, Lawrence JB. The 4q subtelomere harboring the FSHD locus is specifically anchored with peripheral heterochromatin unlike most human telomeres. J Cell Biol. 2004 Oct 25; 167(2):269-79.
          View in: PubMed
        26. Hall LL, Lawrence JB. The cell biology of a novel chromosomal RNA: chromosome painting by XIST/Xist RNA initiates a remodeling cascade. Semin Cell Dev Biol. 2003 Dec; 14(6):369-78.
          View in: PubMed
        27. Moen PT, Johnson CV, Byron M, Shopland LS, de la Serna IL, Imbalzano AN, Lawrence JB. Repositioning of muscle-specific genes relative to the periphery of SC-35 domains during skeletal myogenesis. Mol Biol Cell. 2004 Jan; 15(1):197-206.
          View in: PubMed
        28. Shopland LS, Johnson CV, Byron M, McNeil J, Lawrence JB. Clustering of multiple specific genes and gene-rich R-bands around SC-35 domains: evidence for local euchromatic neighborhoods. J Cell Biol. 2003 Sep 15; 162(6):981-90.
          View in: PubMed
        29. Oh SW, Pope RK, Smith KP, Crowley JL, Nebl T, Lawrence JB, Luna EJ. Archvillin, a muscle-specific isoform of supervillin, is an early expressed component of the costameric membrane skeleton. J Cell Sci. 2003 Jun 1; 116(Pt 11):2261-75.
          View in: PubMed
        30. Hall LL, Clemson CM, Byron M, Wydner K, Lawrence JB. Unbalanced X;autosome translocations provide evidence for sequence specificity in the association of XIST RNA with chromatin. Hum Mol Genet. 2002 Dec 1; 11(25):3157-65.
          View in: PubMed
        31. Shopland LS, Johnson CV, Lawrence JB. Evidence that all SC-35 domains contain mRNAs and that transcripts can be structurally constrained within these domains. J Struct Biol. 2002 Oct-Dec; 140(1-3):131-9.
          View in: PubMed
        32. Hall LL, Byron M, Sakai K, Carrel L, Willard HF, Lawrence JB. An ectopic human XIST gene can induce chromosome inactivation in postdifferentiation human HT-1080 cells. Proc Natl Acad Sci U S A. 2002 Jun 25; 99(13):8677-82.
          View in: PubMed
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