Jeanne B Lawrence PHD
Title Chair and Professor
Institution University of Massachusetts Medical School
Department Cell and Developmental Biology
Address University of Massachusetts Medical School
55 Lake Avenue North
Worcester MA 01655
Telephone 508-856-6015
Email
Other Positions
Institution UMMS - School of Medicine
Department Pediatrics

Institution UMMS - Graduate School of Biomedical Sciences
Department Cell Biology

Institution UMMS - Graduate School of Biomedical Sciences
Department Interdisciplinary Graduate Program

Institution UMMS - Graduate School of Biomedical Sciences
Department MD/PhD Program
Narrative

CDB Department Website

Lawrence Lab Website

Academic Background

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

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

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

1969-197l  Simmons 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

Publications
1. 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
 
2. 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
 
3. 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
 
4. 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
 
5. 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
 
6. 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
 
7. 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
 
8. 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
 
9. 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
 
10. 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
 
11. 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
 
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.
  View in: PubMed
 
13. 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
 
14. 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
 
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.
  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.
  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.
  View in: PubMed
 
18. 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
 
19. 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
 
20. 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
 
21. 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
 
22. 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
 
23. 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
 
24. 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
 
25. 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
 
26. 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
 
27. 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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Keyword
Last Name
Institution
    
 
 
 
Keywords   
RNA, Untranslated
Chromosomes, Human, X
Cell Nucleus
Heterochromatin
X Chromosome Inactivation
See all (169) keywords
Co-Authors  
Bach, Ingolf
Hall-Anderson, Lisa
Imbalzano, Anthony
Jones, Stephen
Smith, Kelly
See all (11) people
Physical Neighbors  
Nickerson, Jeffrey
Hall-Anderson, Lisa
Jungnickel, Melissa
Odgren, Paul
Jones, Peter

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