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Martin, Sara

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Martin

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Martin, Sara
Author's Publications: search.filters.isAuthorOfPublication.e311845e-929d-47a8-9527-041f7eb05f50

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    Inhibition of O-GlcNAc transferase activity reprograms prostate cancer cell metabolism
    (Impact Journals LLC, 2016) Itkonen, Harri M.; Gorad, Saurabh S.; Duveau, Damien Y.; Martin, Sara; Barkovskaya, Anna; Bathen, Tone F.; Moestue, Siver A.; Mills, Ian G.
    Metabolic networks are highly connected and complex, but a single enzyme, O-GlcNAc transferase (OGT) can sense the availability of metabolites and also modify target proteins. We show that inhibition of OGT activity inhibits the proliferation of prostate cancer cells, leads to sustained loss of c-MYC and suppresses the expression of CDK1, elevated expression of which predicts prostate cancer recurrence (p=0.00179). Metabolic profiling revealed decreased glucose consumption and lactate production after OGT inhibition. This decreased glycolytic activity specifically sensitized prostate cancer cells, but not cells representing normal prostate epithelium, to inhibitors of oxidative phosphorylation (rotenone and metformin). Intra-cellular alanine was depleted upon OGT inhibitor treatment. OGT inhibitor increased the expression and activity of alanine aminotransferase (GPT2), an enzyme that can be targeted with a clinically approved drug, cycloserine. Simultaneous inhibition of OGT and GPT2 inhibited cell viability and growth rate, and additionally activated a cell death response. These combinatorial effects were predominantly seen in prostate cancer cells, but not in a cell-line derived from normal prostate epithelium. Combinatorial treatments were confirmed with two inhibitors against both OGT and GPT2. Taken together, here we report the reprogramming of energy metabolism upon inhibition of OGT activity, and identify synergistically lethal combinations that are prostate cancer cell specific.
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    The State of Quality in the NHS in England: a Qualitative Analysis of Interviews With Forty-Three High-Ranking Representatives of the NHS
    (2017-05-12) Martin, Sara
    Recent years have seen dramatic changes in the quality infrastructure of the NHS in England. In addition to the large-scale restructuring that occurred under the 2012 Health and Social Care Act, there have been copious changes intended to address well-publicized and scandalous lapses in the quality of care. Meanwhile, the NHS in England is coping with ever-restrictive budgetary demands. The resultant picture is of dynamic and complex development with multiple players. Given this, a key question is how best to move forward? How to develop a balanced strategy for quality that develops short, medium and long term goals, and can accommodate immediate political priorities? This thesis will attempt to give some answers, based on qualitative set of interviews with over 43 senior leaders – from the Department of Health, Arms Length Bodies, health care providers and commissioners, clinical leaders, patient groups and independent organisations. The resultant analysis – originally published as part of a Health Foundation report - provides an experiential-based perspective of the current approach to quality in the English NHS. In a report (59) released in December 2016, the National Quality Board (NQB) utilized a model derived from these qualitative results to announce their intentions to streamline efforts to promote quality in the NHS. This report was followed by one from NHS Improvement announcing their efforts to develop a National Quality Strategy.