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Jeanne B Lawrence PhD

TitleProfessor
InstitutionUniversity of Massachusetts Medical School
DepartmentNeurology
AddressUniversity of Massachusetts Medical School
55 Lake Avenue North
Worcester MA 01655
Phone508-856-6015
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    Other Positions
    InstitutionUMMS - School of Medicine
    DepartmentNeurology

    InstitutionUMMS - School of Medicine
    DepartmentNeuroNexus Institute

    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

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentNeuroscience


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    Collapse Biography 
    Collapse education and training
    Stephens College, Columbia, MO, United StatesBABiology/Music
    Rutgers University, New Brunswick, NJ, United StatesMSGenetics
    Brown University, Providence, RI, United StatesPHDDevelopment Biology

    Collapse Overview 
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    Non-coding RNA, Repeat Sequences, Heterochromatin Regulation & Nuclear structure: Implications for Disease









    Lawrence Lab Website



    Research Interests


    The Lawrence Lab's research bridges fundamental questions about genome regulation with pursuing the clinical implications of recent advances in the studies of epigenetics. My research interests reflect my inter-disciplinary training in clinical human genetics and fundamental mechanisms of epigenetic regulation.  These interests motivated many years of work to develop new ways to visualize individual genes and RNAs directly within cell structure, particularly in nuclei and chromosomes.  Compelled by a then new idea that gene and chromosome organization was a fundamental component of epigenome programming during development, we developed single-copy gene and nuclear RNA FISH technology, making it possible to map genes not only on chromosomes but within the interphase nucleus.  This early work demonstrated that many “coding” genes and their pre-mRNAs are organized in specific domains or compartments within the mammalian nucleus.  Further developing these approaches in my lab, we demonstrated that RNA from the XIST gene is expressed exclusively from the inactive X-chromosome and coats the structure of the interphase chromosome territory, where it induces heterochromatin modifications which silence the chromosome. These studies were key in establishing the precedent that a large “non-coding” RNA had function, and XIST now remains the preeminent paradigm for RNA regulation of the epigenome and continues to be a focus for my lab’s research. 


    Beginning in about 2007, my lab began an ambitious project to translate discoveries in chromosome biology and epigenetics to a novel approach to correct a chromosomal abnormality, particularly trisomy 21 in Down syndrome.  We were able to demonstrate that the very large XIST gene could be accurately targeted into one extra human chromosome 21 in iPS cells from a Down syndrome patient. Further, the RNA showed a robust capacity to repress transcription across the Chr21 bearing XIST.  This paves the way for a number of new avenues for translational research for Down syndrome ongoing in my lab, including the investigation of specific cell pathologies and pathways directly impacted by trisomy in human Down syndrome stem cells (including stem cell derived organoids or “minibrains”) and in Down syndrome mouse models.  This also now opens a new possibility: that trisomy 21 could be functionally corrected in specific cells by insertion of a single gene, XIST.   


    The ability of a gene from the X- chromosome to induce silencing of an autosome provides evidence that XIST RNA utilizes a genome-wide mechanism to induce heterochromatin and architectural changes that is shared across chromosomes.   Thus, we are also exploring the implications that many repetitive sequences (often still considered simply evolutionary junk) may play a fundamental role in chromosome structure and function, and in shaping the human epigenome.


     


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    Collapse Bibliographic 
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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Hall LL, Byron M, Carone DM, Whitfield TW, Pouliot GP, Fischer A, Jones P, Lawrence JB. Demethylated HSATII DNA and HSATII RNA Foci Sequester PRC1 and MeCP2 into Cancer-Specific Nuclear Bodies. Cell Rep. 2017 Mar 21; 18(12):2943-2956. PMID: 28329686.
      View in: PubMed
    2. Kolpa HJ, Fackelmayer FO, Lawrence JB. SAF-A Requirement in Anchoring XIST RNA to Chromatin Varies in Transformed and Primary Cells. Dev Cell. 2016 Oct 10; 39(1):9-10. PMID: 27728783.
      View in: PubMed
    3. Wang F, Shin J, Shea JM, Yu J, BoŇ°kovic A, Byron M, Zhu X, Shalek AK, Regev A, Lawrence JB, Torres EM, Zhu LJ, Rando OJ, Bach I. Regulation of X-linked gene expression during early mouse development by Rlim. Elife. 2016 Sep 19; 5. PMID: 27642011.
      View in: PubMed
    4. Hall LL, Lawrence JB. RNA as a fundamental component of interphase chromosomes: could repeats prove key? Curr Opin Genet Dev. 2016 Apr; 37:137-47. PMID: 27218204.
      View in: PubMed
    5. Swanson EC, Rapkin LM, Bazett-Jones DP, Lawrence JB. Unfolding the story of chromatin organization in senescent cells. Nucleus. 2015; 6(4):254-60. PMID: 26107557.
      View in: PubMed
    6. Shin J, Wallingford MC, Gallant J, Marcho C, Jiao B, Byron M, Bossenz M, Lawrence JB, Jones SN, Mager J, Bach I. RLIM is dispensable for X-chromosome inactivation in the mouse embryonic epiblast. Nature. 2014 Jul 3; 511(7507):86-9. PMID: 24870238.
      View in: PubMed
    7. 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. PMID: 24581492.
      View in: PubMed
    8. 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. PMID: 24344186.
      View in: PubMed
    9. Lawrence J, Telfer C. Interview: from Down's syndrome to basic epigenetics and back again. Epigenomics. 2013 Dec; 5(6):611-4. PMID: 24283875.
      View in: PubMed
    10. 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. PMID: 23907535.
      View in: PubMed
    11. 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. PMID: 23863942.
      View in: PubMed
    12. 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:Unit 4.15. PMID: 23315927.
      View in: PubMed
    13. 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. PMID: 22722067.
      View in: PubMed
    14. 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. PMID: 22541433.
      View in: PubMed
    15. 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. PMID: 20962847.
      View in: PubMed
    16. 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. PMID: 19704020.
      View in: PubMed
    17. 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. PMID: 19449340.
      View in: PubMed
    18. 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. PMID: 19217333.
      View in: PubMed
    19. 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. PMID: 18809719.
      View in: PubMed
    20. 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. PMID: 18340642.
      View in: PubMed
    21. 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. PMID: 18591425.
      View in: PubMed
    22. 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. PMID: 17846170.
      View in: PubMed
    23. 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. PMID: 17611545.
      View in: PubMed
    24. 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. PMID: 17146760.
      View in: PubMed
    25. 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. PMID: 17145961.
      View in: PubMed
    26. 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. PMID: 16761280.
      View in: PubMed
    27. 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. PMID: 16682630.
      View in: PubMed
    28. 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. PMID: 16533911.
      View in: PubMed
    29. 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. PMID: 15503302.
      View in: PubMed
    30. 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. PMID: 15616869.
      View in: PubMed
    31. 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. PMID: 15504910.
      View in: PubMed
    32. 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. PMID: 15015744.
      View in: PubMed
    33. 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. PMID: 14617810.
      View in: PubMed
    34. 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. PMID: 12975345.
      View in: PubMed
    35. 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. PMID: 12711699.
      View in: PubMed
    36. 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. PMID: 12444100.
      View in: PubMed
    37. 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. PMID: 12490161.
      View in: PubMed
    38. 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. PMID: 12072569.
      View in: PubMed
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