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Jeanne B Lawrence PhD

TitleProfessor
InstitutionUMass Chan Medical School
DepartmentNeurology
AddressUMass Chan Medical School
55 Lake Avenue North
Worcester MA 01655
Phone508-856-6015
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    Other Positions
    InstitutionT.H. Chan School of Medicine
    DepartmentNeurology

    InstitutionT.H. Chan School of Medicine
    DepartmentNeuroNexus Institute

    InstitutionT.H. Chan School of Medicine
    DepartmentPediatrics

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentInterdisciplinary Graduate Program

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentMD/PhD Program

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentNeuroscience


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

    Collapse Overview 
    Collapse Summary
    Lawrence lab research bridges fundamental questions of developmental epigenetics with translational research into the common problem of chromosome abnormalities, particularly Down syndrome.
    Collapse overview

    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 
    Collapse selected publications
    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.
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    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Creamer KM, Larsen EC, Lawrence JB. ZNF146/OZF and ZNF507 target LINE-1 sequences. G3 (Bethesda). 2022 03 04; 12(3). PMID: 35100360.
      Citations:    Fields:    Translation:HumansCells
    2. Kolpa HJ, Creamer KM, Hall LL, Lawrence JB. SAF-A mutants disrupt chromatin structure through dominant negative effects on RNAs associated with chromatin. Mamm Genome. 2022 06; 33(2):366-381. PMID: 34859278.
      Citations:    Fields:    Translation:Cells
    3. Creamer KM, Kolpa HJ, Lawrence JB. Nascent RNA scaffolds contribute to chromosome territory architecture and counter chromatin compaction. Mol Cell. 2021 09 02; 81(17):3509-3525.e5. PMID: 34320406.
      Citations: 7     Fields:    Translation:HumansAnimalsCells
    4. Smith KP, Hall LL, Lawrence JB. Nuclear hubs built on RNAs and clustered organization of the genome. Curr Opin Cell Biol. 2020 06; 64:67-76. PMID: 32259767.
      Citations: 12     Fields:    Translation:HumansCells
    5. Czermi?ski JT, Lawrence JB. Silencing Trisomy 21 with XIST in Neural Stem Cells Promotes Neuronal Differentiation. Dev Cell. 2020 02 10; 52(3):294-308.e3. PMID: 31978324.
      Citations: 18     Fields:    Translation:HumansCells
    6. Chiang JC, Jiang J, Newburger PE, Lawrence JB. Trisomy silencing by XIST normalizes Down syndrome cell pathogenesis demonstrated for hematopoietic defects in vitro. Nat Commun. 2018 12 05; 9(1):5180. PMID: 30518921.
      Citations: 18     Fields:    Translation:HumansAnimalsCells
    7. Wang F, McCannell KN, Boškovi? A, Zhu X, Shin J, Yu J, Gallant J, Byron M, Lawrence JB, Zhu LJ, Jones SN, Rando OJ, Fazzio TG, Bach I. Rlim-Dependent and -Independent Pathways for X Chromosome Inactivation in Female ESCs. Cell Rep. 2017 12 26; 21(13):3691-3699. PMID: 29281819.
      Citations: 8     Fields:    Translation:AnimalsCells
    8. 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 03 21; 18(12):2943-2956. PMID: 28329686.
      Citations: 35     Fields:    Translation:HumansCells
    9. Kolpa HJ, Fackelmayer FO, Lawrence JB. SAF-A Requirement in Anchoring XIST RNA to Chromatin Varies in Transformed and Primary Cells. Dev Cell. 2016 10 10; 39(1):9-10. PMID: 27728783.
      Citations: 22     Fields:    Translation:HumansCells
    10. Wang F, Shin J, Shea JM, Yu J, Boškovi? 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 09 19; 5. PMID: 27642011.
      Citations: 18     Fields:    Translation:Animals
    11. Hall LL, Lawrence JB. RNA as a fundamental component of interphase chromosomes: could repeats prove key? Curr Opin Genet Dev. 2016 04; 37:137-147. PMID: 27218204.
      Citations: 15     Fields:    Translation:Cells
    12. 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.
      Citations: 11     Fields:    Translation:HumansCells
    13. Harada A, Mallappa C, Okada S, Butler JT, Baker SP, Lawrence JB, Ohkawa Y, Imbalzano AN. Spatial re-organization of myogenic regulatory sequences temporally controls gene expression. Nucleic Acids Res. 2015 Feb 27; 43(4):2008-21. PMID: 25653159.
      Citations: 19     Fields:    Translation:AnimalsCells
    14. 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 03; 511(7507):86-9. PMID: 24870238.
      Citations: 32     Fields:    Translation:AnimalsCells
    15. 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.
      Citations: 73     Fields:    Translation:HumansAnimalsCells
    16. 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.
      Citations: 102     Fields:    Translation:HumansAnimalsCells
    17. Lawrence J, Telfer C. Interview: from Down's syndrome to basic epigenetics and back again. Epigenomics. 2013 Dec; 5(6):611-4. PMID: 24283875.
      Citations: 1     Fields:    Translation:HumansCells
    18. 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.
      Citations: 473     Fields:    Translation:AnimalsCells
    19. 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.
      Citations: 138     Fields:    Translation:HumansAnimalsCells
    20. 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.
      Citations: 16     Fields:    Translation:HumansAnimalsCells
    21. 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.
      Citations: 48     Fields:    Translation:HumansAnimalsCells
    22. 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.
      Citations: 19     Fields:    Translation:Animals
    23. Baù D, Sanyal A, Lajoie BR, Capriotti E, Byron M, Lawrence JB, Dekker J, Marti-Renom MA. The three-dimensional folding of the ?-globin gene domain reveals formation of chromatin globules. Nat Struct Mol Biol. 2011 Jan; 18(1):107-14. PMID: 21131981.
      Citations: 157     Fields:    Translation:HumansCells
    24. 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.
      Citations: 80     Fields:    Translation:HumansAnimalsCells
    25. Easwaran HP, Van Neste L, Cope L, Sen S, Mohammad HP, Pageau GJ, Lawrence JB, Herman JG, Schuebel KE, Baylin SB. Aberrant silencing of cancer-related genes by CpG hypermethylation occurs independently of their spatial organization in the nucleus. Cancer Res. 2010 Oct 15; 70(20):8015-24. PMID: 20736368.
      Citations: 16     Fields:    Translation:HumansCells
    26. 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.
      Citations: 25     Fields:    Translation:HumansAnimalsCells
    27. 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 01; 107(4):609-21. PMID: 19449340.
      Citations: 36     Fields:    Translation:HumansCells
    28. 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.
      Citations: 657     Fields:    Translation:HumansAnimalsCells
    29. 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.
      Citations: 16     Fields:    Translation:HumansCells
    30. 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.
      Citations: 54     Fields:    Translation:HumansAnimalsCells
    31. 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.
      Citations: 97     Fields:    Translation:AnimalsCells
    32. 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.
      Citations: 30     Fields:    Translation:HumansCells
    33. Pageau GJ, Hall LL, Ganesan S, Livingston DM, Lawrence JB. The disappearing Barr body in breast and ovarian cancers. Nat Rev Cancer. 2007 08; 7(8):628-33. PMID: 17611545.
      Citations: 56     Fields:    Translation:HumansCells
    34. Chow JC, Hall LL, Baldry SE, Thorogood NP, Lawrence JB, Brown CJ. Inducible XIST-dependent X-chromosome inactivation in human somatic cells is reversible. Proc Natl Acad Sci U S A. 2007 Jun 12; 104(24):10104-9. PMID: 17537922.
      Citations: 37     Fields:    Translation:HumansCells
    35. 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 01; 100(4):835-50. PMID: 17146760.
      Citations: 26     Fields:    Translation:HumansCells
    36. Hutchinson JN, Ensminger AW, Clemson CM, Lynch CR, Lawrence JB, Chess A. A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. BMC Genomics. 2007 Feb 01; 8:39. PMID: 17270048.
      Citations: 470     Fields:    Translation:HumansAnimalsCells
    37. 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 04; 175(5):693-701. PMID: 17145961.
      Citations: 22     Fields:    Translation:HumansAnimalsCells
    38. 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.
      Citations: 108     Fields:    Translation:HumansCells
    39. 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.
      Citations: 108     Fields:    Translation:HumansCells
    40. 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.
      Citations: 23     Fields:    Translation:HumansCells
    41. 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.
      Citations: 8     Fields:    Translation:HumansAnimalsCells
    42. 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.
      Citations: 29     Fields:    Translation:HumansAnimalsCells
    43. 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.
      Citations: 45     Fields:    Translation:HumansCells
    44. 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.
      Citations: 16     Fields:    Translation:HumansAnimalsCells
    45. 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.
      Citations: 53     Fields:    Translation:HumansAnimalsCells
    46. 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.
      Citations: 102     Fields:    Translation:HumansCells
    47. Chow JC, Hall LL, Clemson CM, Lawrence JB, Brown CJ. Characterization of expression at the human XIST locus in somatic, embryonal carcinoma, and transgenic cell lines. Genomics. 2003 Sep; 82(3):309-22. PMID: 12906856.
      Citations: 26     Fields:    Translation:HumansAnimals
    48. 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 01; 116(Pt 11):2261-75. PMID: 12711699.
      Citations: 30     Fields:    Translation:HumansAnimalsCells
    49. 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 01; 11(25):3157-65. PMID: 12444100.
      Citations: 26     Fields:    Translation:HumansCells
    50. 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.
      Citations: 27     Fields:    Translation:HumansCells
    51. 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.
      Citations: 65     Fields:    Translation:HumansCells
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