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Prof Margaret Ashcroft

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Personal Profile

Name: Margaret Ashcroft Email: m.ashcroft@ucl.ac.uk
Title: Prof Tel: 0207 679 0799
Department: Div of Medicine Fax: 0207 679 6211
Position: Address: Division of Medicine, Rayne Building, 5 University Street, London, WC1E 6JF
Research Domain: Cancer, Personalised Medicine Web Page: Personal Web Page

Profile

Research Description

My research programme primarily focuses on elucidating the key signalling mechanisms regulating the hypoxia inducible factor (HIF) pathway as a basis for gaining a better understanding of the role of HIF in disease (e.g. cancer, renal and cardiovascular diseases, and stroke) and translating our basic research findings by identifying novel therapeutics that target the HIF pathway.


Research Activities

Regulation and targeting of the hypoxia inducible factor (HIF) pathway

The VHL-HIF pathway

Education Description

Teaching:
2010-current: CR-UK Centre PhD Programme (Cancer Biology, Translational Research, Experimental Cancer Therapeutics, and Clinical Cancer Studies), UCL Cancer Institute, UCL; primary supervisor
2009-current: MSc Clinical and Experimental Medicine, UCL. ‘Targeting the hypoxia-inducible factor pathway as a new therapeutic approach to cancer treatment’ seminars; primary supervisor
2009-current: MSc Cancer Course, UCL. ‘Hypoxia signalling in cancer’ seminars
2009-current: PhD Programme in Drug Discovery, UCL; co-supervisor 
2009-current: BHF PhD Programme in Cardiovascular Biomedicine, UCL; primary supervisor
2007-2008: MSc Medical Oncology Course, ICR. ‘Hypoxia and angiogenesis’ seminars

UCL Collaborators

Prof Barbara Pedley; Prof David Gems; Prof Tony Segal; Prof Patrick Maxwell; Prof Michael Duchen; Prof Steve Wilson; Prof Chris Boshoff; Prof Stephen Caddick

External Collaborators

Publications

    2014

    • Hickin JA, Ahmed A, Fucke K, Ashcroft M, Jones K (2014). The synthesis and structure revision of NSC-134754. CHEMICAL COMMUNICATIONS, 50(10), 1238 - 1240. doi:10.1039/c3cc48189a

    2013

    • Luong LA, Fragiadaki M, Smith J, Boyle J, Lutz J, Dean JL, Harten S, Ashcroft M, Walmsley SR, Haskard DO, Maxwell PH, Walczak H, Pusey C, Evans PC (2013). Cezanne Regulates Inflammatory Responses to Hypoxia in Endothelial Cells by Targeting TRAF6 for Deubiquitination.. doi:10.1161/CIRCRESAHA.111.300119.
    • Selvarajah J, Nathawat K, Moumen A, Ashcroft M, Carroll VA (2013). Chemotherapy-mediated p53-dependent DNA damage response in clear cell renal cell carcinoma: role of the mTORC1/2 and hypoxia-inducible factor pathways. CELL DEATH & DISEASE, 4, - . doi:10.1038/cddis.2013.395
    • Luong LEA, Fragiadaki M, Smith J, Boyle J, Lutz J, Dean JL, Harten S, Ashcroft M, Walmsley SR, Haskard DO, Maxwell PH, Walczak H, Pusey C, Evans PC (2013). Cezanne regulates inflammatory responses to hypoxia in endothelial cells by targeting TRAF6 for deubiquitination.. Circ Res, 112(12), 1583 - 1591. doi:10.1161/CIRCRESAHA.111.300119
    • Baker LC, Boult JK, Jamin Y, Gilmour LD, Walker-Samuel S, Burrell JS, Ashcroft M, Howe FA, Griffiths JR, Raleigh JA, van der Kogel AJ, Robinson SP (2013). Evaluation and Immunohistochemical Qualification of Carbogen-Induced ΔR2* as a Noninvasive Imaging Biomarker of Improved Tumor Oxygenation.. Int J Radiat Oncol Biol Phys, , - . doi:10.1016/j.ijrobp.2013.04.051

    2012

    • Wilson GK, Brimacombe CL, Rowe IA, Reynolds GM, Fletcher NF, Stamataki Z, Bhogal RH, Simoes ML, Ashcroft M, Afford SC, Mitry RR, Dhawan A, Mee CJ, Huebscher SG, Balfe P, McKeating JA (2012). A dual role for hypoxia inducible factor-1 alpha in the hepatitis C virus lifecycle and hepatoma migration. JOURNAL OF HEPATOLOGY, 56(4), 803 - 809.
    • Yang J, Staples O, Thomas LW, Briston T, Robson M, Poon E, Simões ML, El-Emir E, Buffa FM, Ahmed A, Annear NP, Shukla D, Pedley BR, Maxwell PH, Harris AL, Ashcroft M (2012). Human CHCHD4 mitochondrial proteins regulate cellular oxygen consumption rate and metabolism and provide a critical role in hypoxia signaling and tumor progression.. J Clin Invest, 122(2), 600 - 611. doi:10.1172/JCI58780
    • Baker LC, Boult JK, Walker-Samuel S, Chung YL, Jamin Y, Ashcroft M, Robinson SP (2012). The HIF-pathway inhibitor NSC-134754 induces metabolic changes and anti-tumour activity while maintaining vascular function.. Br J Cancer, 106(10), 1638 - 1647. doi:10.1038/bjc.2012.131

    2011

    • Ahmed A, Yang J, Maya-Mendoza A, Jackson DA, Ashcroft M (2011). Pharmacological activation of a novel p53-dependent S-phase checkpoint involving CHK-1.. Cell Death Dis, 2, e160 - . doi:10.1038/cddis.2011.42
    • Harten SK, Esteban MA, Shukla D, Ashcroft M, Maxwell PH (2011). Inactivation of the von Hippel-Lindau tumour suppressor gene induces Neuromedin U expression in renal cancer cells.. Mol Cancer, 10, 89 - . doi:10.1186/1476-4598-10-89
    • Khan MN, Bhattacharyya T, Andrikopoulos P, Esteban MA, Barod R, Connor T, Ashcroft M, Maxwell PH, Kiriakidis S (2011). Factor inhibiting HIF (FIH-1) promotes renal cancer cell survival by protecting cells from HIF-1α-mediated apoptosis.. Br J Cancer, 104(7), 1151 - 1159. doi:10.1038/bjc.2011.73
    • Briston T, Yang J, Ashcroft M (2011). HIF-1α localization with mitochondria: a new role for an old favorite?. Cell Cycle, 10(23), 4170 - 4171. doi:10.4161/cc.10.23.18565

    2010

    • Harten SK, Ashcroft M, Maxwell PH (2010). Prolyl hydroxylase domain inhibitors: a route to HIF activation and neuroprotection.. Antioxid Redox Signal, 12(4), 459 - 480. doi:10.1089/ars.2009.2870
    • Ahmed A, Ashcroft M (2010). TRP-ing off the p53 apoptotic switch.. Pigment Cell and Melanoma Research, 23(5), 581 - 582. doi:10.1111/j.1755-148X.2010.00746.x

    2009

    • Poon P, Harris AL, Ashcroft M (2009). Targeting the hypoxia-inducible factor (HIF) pathway in cancer. Expert Review in Molecular Medicine, (11:e26), - . doi:10.1017/S1462399409001173
    • Yang J, Ahmed A, Poon E, Perusinghe N, Brandon AD, Box G, Valenti M, Eccles S, Rouschop K, Wouters B, Ashcroft M (2009). Small-Molecule Activation of p53 Blocks Hypoxia-Inducible Factor 1 alpha and Vascular Endothelial Growth Factor Expression In Vivo and Leads to Tumor Cell Apoptosis in Normoxia and Hypoxia. MOL CELL BIOL, 29(8), 2243 - 2253. doi:10.1128/MCB.00959-08
    • Barod R, Domin J, Eccles S, O' Brien TS, Ashcroft M, Maxwell PH (2009). PTEN CAN FUNCTION AS A TUMOUR SUPPRESSOR IN CLEAR CELL RENAL CARCINOMA. EUR UROL SUPPL, 8(4), 377 - 377.
    • Barod R, Domin J, Eccles S, Ashcroft M, O'Brien TS, Maxwell PH (2009). PTEN can function as a tumour suppressor in clear cell renal carcinoma.
    • Yang J, Ahmed A, Poon E, Perusinghe N, de HBA, Box G, Valenti M, Eccles S, Rouschop K, Wouters B, Ashcroft M (2009). Small molecule activation of p53 blocks HIF-1α and VEGF 1 expression in vivo and leads to tumor cell apoptosis in normoxia and hypoxia. Molecular and Cellular Biology, , - .
    • Yang J, Ahmed A, Ashcroft M (2009). Activation of a unique p53-dependent DNA damage response.. Cell Cycle, 8(10), 1630 - 1632.
    • Maxwell PH, Ashcroft M (2009). Angiogenic Cancer Therapy. Brit J Cancer, 100, 1515 - 1516.
    • Alam H, Weck J, Maizels E, Park Y, Lee EJ, Ashcroft M, Hunzicher-Dunn M (2009). Role of the phosphatidylinositol-3-kinase and extracellular regulated kinase pathways in the induction of hypoxia-inducible factor (HIF)-1 activity and the HIF-1 target vascular endothelial growth factor in ovarian granulosa cells in response to follicle-stimulating hormone. Endocrinology, 150(2), 915 - 928.
    • Palmer CD, Rahman FZ, Sewell GW, Ahmed A, Ashcroft M, Bloom SL, Segal AW, Smith AM (2009). Diminished macrophage apoptosis and reactive oxygen species generation after phorbol ester stimulation in Crohn's disease.. PLoS One, 4(11), e7787 - . doi:10.1371/journal.pone.0007787
    • Harten S, Ashcroft M, Maxwell PH (2009). Prolyl hydroxyase inhibitors: a route to HIF activation and neuroprotection.. Antioxidants and Redox Signaling, 12(4), 459 - 480.
    • Palmer CD, Rahman FZ, Sewell GW, Ahmed A, Ashcroft M, Bloom SL, Segal AW, Smith AM (2009). Diminished Macrophage Apoptosis and Reactive Oxygen Species Generation after Phorbol Ester Stimulation in Crohn’s Disease. PLoS One, 4(11), e7787 - .

    2008

    • Carroll VA and Ashcroft M (2008). Regulation of angiogenic factors by HDM2 in renal cell carcinoma.. Cancer Research, 68(2), 545 - 552.

    2007

    • Sutton KM, Hayat S, Chau NM, Cook S, Pouyssegur J, Ahmed A, Perusinghe N, Le FR, Yang J, Ashcroft , M (2007). Selective inhibition of MEK1/2 reveals a differential requirement for ERK1/2 signalling in the regulation of HIF-1 in response to hypoxia and IGF-1.. Oncogene, 26(27), 3920 - 3929.

    2006

    • Stimson L, Chau NM, Workman P, Ashcroft M, Aherne GW (2006). Histone deacetylase inhibitors (HDACIs) induce HIF-1 transcriptional activity..
    • Yang J, Ashcroft M (2006). p53-mediated effects on the HIF pathway in normoxia and hypoxia..
    • Carroll VA, Ashcroft M (2006). Role of HIF-1α versus HIF-2α in the regulation of HIF target genes: Implications for targeting the HIF pathway..
    • Anderson CJ, Hoare SF, Ashcroft M, Bilsland AE, Keith WN (2006). Hypoxic regulation of telomerase gene expression by transcriptional and post-transcriptional mechanisms.. Oncogene, 25(1), 61 - 69.
    • Carroll VA and Ashcroft M (2006). Role of hypoxia-inducible factor (HIF)-1alpha versus HIF-2alpha in the regulation of HIF target genes in response to hypoxia, insulin-like growth factor-I, or loss of von Hippel-Lindau function: implications for targeting the HIF pathway.. Cancer Research, 66(12), 6264 - 6270.

    2005

    • Bárdos JI, Ashcroft , M (2005). Negative and positive regulation of HIF-1: a complex network.. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1755(2), 107 - 120.
    • Chau NM, Rogers P, Aherne W, Carroll V, Collins I, McDonald E, Workman P, Ashcroft M (2005). Identification of novel small molecule inhibitors of hypoxia-inducible factor-1 that differentially block hypoxia-inducible factor-1 activity and hypoxia-inducible factor-1alpha induction in response to hypoxic stress and growth factors.. Cancer Research, 65(11), 4918 - 4928.
    • Carroll VA, Chau NM, Wilsher N, Raynaud F, Eccles S, Ashcroft M (2005). Regulation and targeting of the hypoxia-inducible pathway.
    • Carroll V, Ashcroft M (2005). Role of HDM2 in IGF induced HIF expression and activation of target genes..
    • Carroll VA and Ashcroft M (2005). Targeting the molecular basis for tumour hypoxia.. Expert Rev Mol Med, 7(6), 1 - 16.

    2004

    • Chau NM, Ashcroft M (2004). Akt2: a role in breast cancer metastasis.. Breast Cancer Res, 6(1), 55 - 57.
    • Chau NM, Rogers P, Aherne GW, McDonald T, Workman P, Ashcroft M (2004). Targeting hypoxia inducible factor-1..
    • Ashcroft M, Ludwig RL, Woods DB, Copeland TD, Weber HO, MacRae EJ, Vousden KH (2004). Phosphorylation of HDM2 by Akt.. Oncogene, 21(13), 1955 - 1962.
    • Bárdos JI, Chau NM, Ashcroft , M (2004). Growth factor-mediated induction of HDM2 positively regulates hypoxia-inducible factor 1alpha expression.. Molecular and Cellular Biology, 24(7), 2905 - 2914.
    • Kaufman B, Scharf O, Arbeit J, Ashcroft M, Brown JM, Bruick RK, Chapman JD, Evans SM, Giaccia AJ, Harris AL, Huang E, Johnson R, Kaelin WJ, Koch CJ, Maxwell P, Mitchell J, Neckers L, Powis G, Rajendran J, Semenza GL, Simons J, Storkebaum E, Welch MJ, Whitelaw M, Melillo G, Ivy SP (2004). Proceedings of the Oxygen Homeostasis/Hypoxia Meeting.. Cancer Research, 64(9), 3350 - 3356. doi:10.1164/rccm.200402-230OC
    • Bárdos JI, Ashcroft M (2004). Regulation of HIF-1 activity and function.. Bioessays, 26(3), 262 - 269.

    2003

    • Chau NM, Rogers P, Aherne W, Workman P, Ashcroft M (2003). Development and characterisation of a cell-based system for identification of novel HIF-1 inhibitors..
    • Bárdos JI, Chau NM, Ashcroft M (2003). Oncogenic pathways regulating HIF-1..
    • Anderson CJ, Ashcroft M, Keith WN (2003). Hypoxic regulation of telomerase gene expression..

    2000

    • Ashcroft M, Vousden KH (2000). The p53 Tumor Suppressor Protein.. In Fisher DE (Ed.), Tumor Suppressor Genes in Human Cancer (pp. 159 - 181). : Humana Press.
    • Ashcroft M, Taya Y, Vousden KH (2000). Stress signals utilize multiple pathways to stabilize p53.. Molecular and Cellular Biology, 20(9), 3224 - 3233.
    • Lohrum MA, Ashcroft M, Kubbutat MH, Vousden KH (2000). Contribution of two independent MDM2-binding domains in p14(ARF) to p53 stabilization.. Current Biology, 10(9), 539 - 542.
    • Pise-Masison CA, Mahieux R, Jiang H, Ashcroft M, Radonovich M, Duvall J, Guillerm C, Brady JN (2000). Inactivation of p53 by human T-cell lymphotropic virus type 1 Tax requires activation of the NF-kappaB pathway and is dependent on p53 phosphorylation.. Molecular and Cellular Biology, 20(10), 3377 - 3386.
    • Lohrum MA, Ashcroft M, Kubbutat MH, Vousden KH (2000). Identification of a cryptic nucleolar-localization signal in MDM2.. Nature Cell Biology, 2(3), 179 - 181.
    • Nakano K, Bálint E, Ashcroft M, Vousden KH (2000). A ribonucleotide reductase gene is a transcriptional target of p53 and p73.. Oncogene, 19(37), 4283 - 4289.

    1999

    • Ashcroft M, Stephens RM, Hallberg B, Downward J, Kaplan DR (1999). The selective and inducible activation of endogenous PI 3-kinase in PC12 cells results in efficient NGF-mediated survival but defective neurite outgrowth.. Oncogene, 18(32), 4586 - 4597.
    • Ashcroft M, Vousden KH (1999). Regulation of p53 stability. Oncogene, 18(53), 7637 - 7643.
    • Ashcroft M, Kubbutat MH, Vousden KH (1999). Regulation of p53 function and stability by phosphorylation.. Molecular and Cellular Biology, 19(3), 1751 - 1758.

    1998

    • Hallberg B, Ashcroft M, Loeb DM, Kaplan DR, Downward J (1998). Nerve growth factor induced stimulation of Ras requires Trk interaction with Shc but does not involve phosphoinositide 3-OH kinase.. Oncogene, 17(6), 691 - 697.
    • Kubbutat MH, Ludwig RL, Ashcroft M, Vousden KH (1998). Regulation of Mdm2-directed degradation by the C terminus of p53.. Molecular and Cellular Biology, 18(10), 5690 - 5698.

    1994

    • Allen SJ, Dawbarn D, Eckford SD, Wilcock GK, Ashcroft M, Colebrook SM, Feeney R, MacGowan SH (1994). Cloning of a non-catalytic form of human trkB and distribution of messenger RNA for trkB in human brain.. Neuroscience, 60(3), 825 - 834.
    • Dawbarn D, Allen SJ, Ashcroft M, Colebrook SM, Feeney R, Macgowan SH (1994). Cloning of a human trkB gene and distribution in human brain by in situ hybridisation.

    1993

    • Colebrook SM, Feeney R, Macgowan SH, Allen SJ, Ashcroft M, Dawbarn D (1993). Construction of Beta-NGF BDNF chimeric genes and expression of recombinant proteins.
    • Allen SJ, Ashcroft M, Colebrook SM, Feeney R, Macgowan SH, Dawbarn D (1993). Distribution of trkB in rat brain by in situ hybridisation..

    • Baker L, Boult J, Walker-Samuel S, Jamin Y, Ashcroft M, Robinson S (). An MRI and histological investigation of the acute response of orthotopic PC3 prostate tumours to the HIF pathway inhibitor NSC-134754 in vivo.