The extracellular matrix (ECM) provides structural and mechanical support to tissues and modulates cell phenotype and behaviour in health and disease. Changes in ECM composition can permit carcinoma cell metastasis. Synthetic environments that mimic native ECM have many applications in tissue engineering and clinical procedures. Thrombospondins are a conserved family of ECM proteins that impact on the organisation of collagen-based ECMs and cell activities. We are studying the cellular mechanisms by which thrombospondins modulate ECM organisation and activate cell signaling pathways that promote cell migration. Ongoing goals are to elucidate fundamental mechanisms and develop agents that can modulate the retention of thrombospondins within ECM. We also study the role of cell-ECM interactions in cell migration and cancer metastasis, with a focus on fascin-1, an actin-bundling protein that correlates clinically with aggressive carcinomas and may promote metastasis. Molecular, cellular, biochemical, imaging and bioinformatics approaches are used to address these questions. Possible Ph.D. projects can relate to either research area.
1. Kim+, D.J., Christofidou+, E.D., Keene, D.R, Milde, H.M. and Adams, J.C. (2015). Inter-Molecular Interactions Of Thrombospondins Drive Their Accumulation In Extracellular Matrix (+co-first-authors). Mol. Biol. Cell. 26:2640-54. doi:10.1091/mbc.E14-05-0996.
2. Hellewell, A.L., Gong, X., Schärich, K., Christofidou, E.D. and Adams, J.C. (2015). Modulation of the Extracellular Matrix Patterning of Thrombospondins by Actin Dynamics and Thrombospondin Oligomer State. Bioscience Reports 35 (3) e00218; DOI: 10.1042/BSR20140168.
3. Tan, V.Y., Lewis, S.J., Adams, J.C. and Martin, R.M. (2013). Association of fascin-1 with Mortality, Disease Progression and Metastasis in carcinomas: a systematic review and meta-analysis. BMC Medicine 11:52 doi:10.1186/1741-7015-11-52.
4. Adams, J.C. (2014). Fascin-1 as a prospective biomarker and therapeutic target in colorectal cancer. Expert Review of Molecular Diagnostics 15:41-8.