Increasing the physiological relevance of cell cultures provides a better understanding of the in vivo situation. Three-dimensional (3D) cell culture systems and spheroids have gained increasing interest in drug discovery as they have the ability to provide more human relevant insights compared to traditional two-dimensional (2D) monolayer cultures. Culturing cells under flow allows transport of oxygen and nutrients and removal of waste products. Dynamic conditions more accurately mimic the environment within the body and therefore provide more predictive data than static conditions. Co-culture enables improved understanding of interactions between cell populations.
Session Chair: Professor Trevor Dale
Director of Technology (Cardiff University)
Trevor did his 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 he became interested in the role of signalling pathways in development. Following a postdoctoral fellowship at Baylor College of Medicine in Houston, he established a research group at the Institute of Cancer Research in London in 1991. His group moved to Cardiff in November 2003.
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. The laboratory studies normal and oncogenic Wnt signalling using approaches ranging from biochemistry/structural biology, through cell and organoid based assays to murine models.
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Carotenuto, P.et al. 2017. Wnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers. Gut 66(7), pp. 1268-1277. (10.1136/gutjnl-2016-312278)
Dietrich, L.et al. 2017. Overcoming the low cell permeability of a β-Catenin-targeting stapled peptide thereby enabling potent inhibition of Wnt signaling. Cell Chemical Biology
Kay, S.et al. 2017. The role of the Hes1 crosstalk hub in Notch-Wnt interactions of the intestinal crypt. PLoS Computational Biology 13(2), article number: e1005400. (10.1371/journal.pcbi.1005400)
Clarke, P.et al. 2016. Assessing the mechanism and therapeutic potential of modulators of the human Mediator complex-associated protein kinases. eLife 5, article number: e20722. (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)
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)
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)
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To be confirmed
Kate Harper (PerkinElmer) - Imaging Bile Canaliculi in 3D Liver Microtissues using the Opera Phenix High Content Screening System
Nuria Abajo Lima (Cardiff University) - Scale up of organoid expansion and fractionation for their widespread use in preclinical drug discovery
Jessica Pinheiro de Lucena-Thomas (University of Bath) - Microgel Matrices for Human Cancer Organoid Production