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Search Results to Jeanne B Lawrence PhD

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One or more keywords matched the following properties of Lawrence, Jeanne

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keywords Nuclear Structure
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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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One or more keywords matched the following items that are connected to Lawrence, Jeanne

Item TypeName
Academic Article The cell biology of a novel chromosomal RNA: chromosome painting by XIST/Xist RNA initiates a remodeling cascade.
Academic Article The 4q subtelomere harboring the FSHD locus is specifically anchored with peripheral heterochromatin unlike most human telomeres.
Academic Article Molecular anatomy of a speckle.
Academic Article Defining early steps in mRNA transport: mutant mRNA in myotonic dystrophy type I is blocked at entry into SC-35 domains.
Academic Article Gene associations: true romance or chance meeting in a nuclear neighborhood?
Academic Article Changing nuclear landscape and unique PML structures during early epigenetic transitions of human embryonic stem cells.
Academic Article Evidence that all SC-35 domains contain mRNAs and that transcripts can be structurally constrained within these domains.
Academic Article A multifaceted FISH approach to study endogenous RNAs and DNAs in native nuclear and cell structures.
Academic Article A long noncoding RNA mediates both activation and repression of immune response genes.
Academic Article Clustering of multiple specific genes and gene-rich R-bands around SC-35 domains: evidence for local euchromatic neighborhoods.
Academic Article c-Myc localization within the nucleus: evidence for association with the PML nuclear body.
Academic Article An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles.
Academic Article Heterochromatin instability in cancer: from the Barr body to satellites and the nuclear periphery.
Concept RNA, Small Nuclear
Concept RNA, Nuclear
Concept Nuclear Proteins
Concept Heterogeneous-Nuclear Ribonucleoproteins
Concept Chromosome Structures
Concept Ribonucleoproteins, Small Nuclear
Concept Protein Structure, Tertiary
Academic Article Spatial re-organization of myogenic regulatory sequences temporally controls gene expression.
Academic Article A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains.
Academic Article Aberrant silencing of cancer-related genes by CpG hypermethylation occurs independently of their spatial organization in the nucleus.
Academic Article Demethylated HSATII DNA and HSATII RNA Foci Sequester PRC1 and MeCP2 into Cancer-Specific Nuclear Bodies.
Academic Article Nuclear hubs built on RNAs and clustered organization of the genome.

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  • Structure