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Last Name

Lisa L Hall-Anderson PhD

TitleAssociate Professor
InstitutionUniversity of Massachusetts Medical School
AddressUniversity of Massachusetts Medical School
55 Lake Avenue North
Worcester MA 01655
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    InstitutionUMMS - School of Medicine

    InstitutionUMMS - Graduate School of Biomedical Sciences

    Collapse Biography 
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    Colorado College, Colorado Springs, CO, United StatesBABiology
    University of California, Davis, Davis, CA, United StatesPHDGenetics

    Collapse Overview 
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    Dr. Hall collaborates with Dr. Lawrence on research projects and her main research interest is studying how long non-coding RNAs interact with chromatin, the functional importance of the repeat genome in gene regulation and nuclear structure and silencing the extra chromosome 21 in Down syndrome patient cells using targeted integration of an XIST transgene.

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    I collaborate with Dr. Jeanne Lawrence in the Department of Neurology, and have been in her lab since 1999. Her research bridges fundamental questions about genome regulation with pursuing the clinical implications of recent advances in our studies of epigenetics. The genome is not a linear entity, but exists as a complex three-dimensional structure within a highly complex nuclear structure. The lab’s focus is to investigate the functional organization of the nucleus and how it regulates gene expression during differentiation and disease, and whether these mechanisms can be co-opted for therapeutic purposes.

    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 originally identified in other labs as a potential key to the X-inactivation process, however since the RNA did not encode an open-reading frame it was a mystery as to how it functioned. Using powerful molecular cytology approaches first developed in the Lawrence lab, we were able to demonstrate that the XIST gene produced a stable, functional nuclear non-coding RNA that actually “paints” the entire inactive X-chromosome. XIST RNA became the first lncRNA and established the precedent for a new type of functional nuclear RNA involved in chromatin regulation.

    We continue to study how XIST RNA (and other lncRNAs), interacts with the chromosome, and what DNA sequences and chromosomal proteins impact this process, using transgenics and bioinformatics as well as cytological epigenetics. We are also pursuing a novel translational approach for gene therapy in Down syndrome that stems from these advances in understanding non-coding RNA and chromosome regulation

    Beginning in about 2007, we 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 the 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 (shared by all chromosomes) may play a fundamental role in chromosome structure and function, and in shaping the human epigenome.

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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.
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    1. 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
    2. 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
    3. 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
    4. 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
    5. 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
    6. Hall LL, Lawrence JB. XIST RNA and architecture of the inactive X chromosome: implications for the repeat genome. Cold Spring Harb Symp Quant Biol. 2010; 75:345-56. PMID: 21447818; PMCID: PMC3143471.
    7. 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
    8. 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
    9. 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
    10. 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
    11. 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
    12. 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
    13. 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; PMCID: PMC1891207.
    14. 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
    15. 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
    16. 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
    17. 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
    18. Hoffman LM, Hall L, Batten JL, Young H, Pardasani D, Baetge EE, Lawrence J, Carpenter MK. X-inactivation status varies in human embryonic stem cell lines. Stem Cells. 2005 Nov-Dec; 23(10):1468-78. PMID: 16123389.
      View in: PubMed
    19. 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
    20. 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
    21. 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.
      View in: PubMed
    22. 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
    23. 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
    24. Chow JC, Hall LL, Lawrence JB, Brown CJ. Ectopic XIST transcripts in human somatic cells show variable expression and localization. Cytogenet Genome Res. 2002; 99(1-4):92-8. PMID: 12900550.
      View in: PubMed
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