个人简介
I did my undergraduate in Biochemistry at Imperial College and then completed a PhD on interferon signal transduction at the Imperial Cancer Research Fund in 1989 (now Cancer Research UK, London Research Centre). During this time I became interested in the role of signalling pathways in development. Following a postdoctoral fellowship at Baylor College of Medicine in Houston, I established a research group at the Institute of Cancer Research in London in 1991.
My group moved to Cardiff in November 2003.
研究领域
The primary focus of research in the group is the regulation of the Wnt signal transduction pathway. Wnts together with other peptide ligands including the FGF, EGF, TGF-β and hedgehog families orchestrate cell-cell interactions throughout development. Much of the specificity of each ligand's function is controlled by intracellular pathways that are activated at the cell surface. Components of the Wnt/β-catenin pathway are frequently mutated in human cancer. This laboratory studies normal and oncogenic Wnt signalling using approaches ranging from biochemistry/structural biology, through cell and organoid based assays to murine models.
近期论文
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Clarke, P.et al. 2016. Assessing the mechanism and therapeutic potential of modulators of the human Mediator complex-associated protein kinases. eLife 5 (10.7554/eLife.20722)
Jardé, T.et al. 2016. Wnt and Neuregulin1/ErbB signalling extends 3D culture of hormone responsive mammary organoids. Nature Communications 7, article number: 13207. (10.1038/ncomms13207) pdf
Carotenuto, P.et al. 2016. Wnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers. Gut , pp. gutjnl-2016. (10.1136/gutjnl-2016-312278) pdf
Czodrowski, P.et al. 2016. Structure-based optimization of potent, selective, and orally bioavailable CDK8 inhibitors discovered by high-throughput screening. Journal of Medicinal Chemistry 59(20), pp. 9337-9349. (10.1021/acs.jmedchem.6b00597) pdf
Mallinger, A.et al. 2016. Discovery of potent, selective, and orally bioavailable small-molecule modulators of the mediator complex-associated kinases CDK8 and CDK19. Journal of Medicinal Chemistry 59(3), pp. 1078-1101. (10.1021/acs.jmedchem.5b01685)
Freeman, J.et al. 2015. A functional connectome: regulation of Wnt/TCF-dependent transcription by pairs of pathway activators. Molecular Cancer 14(1), article number: 206. (10.1186/s12943-015-0475-1) pdf
Rada, P.et al. 2015. WNT-3A regulates an Axin1/NRF2 complex that regulates antioxidant metabolism in hepatocytes. Antioxidants & Redox Signaling 22(7), pp. 555-571. (10.1089/ars.2014.6040) pdf
Mallinger, A.et al. 2015. Discovery of potent, orally bioavailable, small-molecule inhibitors of WNT signaling from a cell-based pathway screen. Journal of Medicinal Chemistry 58(4), pp. 1717-1735. (10.1021/jm501436m)
Dale, T.et al. 2015. A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease. Nature Chemical Biology 11, pp. 973-980. (10.1038/nchembio.1952)
Carotenuto, M.et al. 2014. H-Prune through GSK-3β interaction sustains canonical WNT/β-catenin signaling enhancing cancer progression in NSCLC. Oncotarget 5(14), pp. 5736-5749.