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Search Results to Lisa L Hall-Anderson PhD

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One or more keywords matched the following properties of Hall-Anderson, Lisa

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keywords Noncoding RNA
overview

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.


One or more keywords matched the following items that are connected to Hall-Anderson, Lisa

Item TypeName
Academic Article Unbalanced X;autosome translocations provide evidence for sequence specificity in the association of XIST RNA with chromatin.
Academic Article The cell biology of a novel chromosomal RNA: chromosome painting by XIST/Xist RNA initiates a remodeling cascade.
Academic Article The X chromosome is organized into a gene-rich outer rim and an internal core containing silenced nongenic sequences.
Academic Article An ectopic human XIST gene can induce chromosome inactivation in postdifferentiation human HT-1080 cells.
Academic Article A long noncoding RNA mediates both activation and repression of immune response genes.
Academic Article 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.
Academic Article X-inactivation reveals epigenetic anomalies in most hESC but identifies sublines that initiate as expected.
Academic Article AURKB-mediated effects on chromatin regulate binding versus release of XIST RNA to the inactive chromosome.
Academic Article Maternal Rnf12/RLIM is required for imprinted X-chromosome inactivation in mice.
Concept RNA, Untranslated
Academic Article Stable C0T-1 repeat RNA is abundant and is associated with euchromatic interphase chromosomes.
Academic Article Characterization of expression at the human XIST locus in somatic, embryonal carcinoma, and transgenic cell lines.
Academic Article Inducible XIST-dependent X-chromosome inactivation in human somatic cells is reversible.
Academic Article XIST RNA and architecture of the inactive X chromosome: implications for the repeat genome.
Academic Article X-inactivation status varies in human embryonic stem cell lines.
Academic Article Ectopic XIST transcripts in human somatic cells show variable expression and localization.

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  • Noncoding RNA