Browsing by Author "Watson, Lauren"

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    Elucidating the molecular basis of a novel autosomal dominant fibrotic syndrome
    (2009) Watson, Lauren; Mayosi, B M
    A novel fibrotic syndrome was recently reported in a South African family, characterised by poikiloderma, tendon contracture and progressive pulmonary fibrosis. The pathological hallmark of this autosomal dominant condition is abnormal fibrosis of the skin, tendons and viscera, with variable penetrance. A candidate gene approach was adopted to investigate the molecular basis of this disease.
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    Novel cell models for the study of spinocerebellar ataxia type 7 pathogenesis and therapy in a South African patient cohort
    (2012) Watson, Lauren; Greenberg, Jacquie; Wood, Matthew
    Spinocerebellar ataxia type 7 (SCA7) is a dominantly-inherited neurodegenerative disease, resulting from a CAG trinucleotide repeat expansion in the ataxin-7 gene. The Ataxin-7 protein is known to play a role in transcriptional regulation through association with cellular histone acetylation complexes, and several studies have highlighted the role of transcriptional dysregulation, caused by the presence of mutant Ataxin-7, in the neuronal dysfunction that precedes the onset of disease symptoms.This study aimed to establish patient-derived cell models of SCA7, for use in the investigation of pathogenesis (with particular reference to transcriptional alterations), and in the evaluation of previously-developed therapies for the disease.The high prevalence of SCA7 in the South African population, as a result of a founder effect, makes this disease particularly amenable to allele-specific RNA interference (RNAi)-based therapy. Thus, this study also evaluated the feasibility of these cell models as a vehicle to test previously-developed RNAi therapeutics, using the alteration of expression of key transcripts as a phenotypic marker. SCA7 patient and control dermal fibroblasts were reprogrammed to pluripotency by retroviral transduction. The resultant induced pluripotent stem cell (iPSC) lines were characterised with respect to endogenous markers of pluripotency, differentiation capacity and transgene silencing. These cells were then subjected to neuronal differentiation, the success of which was confirmed by the expression of early neuronal markers.