About the Project
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 and the build-up of ECM is central to the chronic pathology of tissue fibrosis. 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 through effects on collagen fibril assembly, and how ECM activates cell-signaling pathways that promote cell migration. Ongoing goals are to elucidate fundamental mechanisms and potentially develop agents that can modulate the retention of thrombospondins within ECM. Another area of interest is the role of cell-ECM interactions in cell migration and cancer metastasis, with the goal of altering the microenvironment through modulation of ECM production, secretion, and composition. Molecular, cellular, biochemical, imaging and bioinformatics approaches are used to address these questions. Possible Ph.D. (or Master’s by Research) projects can relate to any research area.
1. Rosini S, Pugh N, Bonna AM, Hulmes DJS, Farndale RW, Adams JC. (2018). Thrombospondin-1 promotes matrix homeostasis by interacting with collagen and lysyl oxidase precursors and collagen cross-linking sites. Sci Signal. 11(532). pii: eaar2566.
2. Lommel M, Strompen J, Hellewell AL, Balasubramanian GP, Christofidou ED, Thomson AR, Boyle AL, Woolfson DN, Puglisi K, Hartl M, Holstein TW, Adams JC, Özbek S. (2018). Hydra Mesoglea Proteome Identifies Thrombospondin as a Conserved Component Active in Head Organizer Restriction. Sci Rep. 8(1):11753. doi: 10.1038/s41598-018-30035-2.
3. Hellewell, A.L., Rosini, S. and Adams, J.C. (2017). A Rapid, Scalable Method for Isolation, Functional Study and Analysis of Cell-Derived Extracellular Matrix. Journal of Visualized Experiments, 2017 Jan 4. (119). doi: 10.3791/55051.
4. Shoemark, D.K, Ziegler, B., Watanabe, H., Strompen, J., Tucker, R.P., Özbek, S., Adams, J.C. (2019). Emergence of a Thrombospondin Superfamily at the Origin of Metazoans. Molecular Biology and Evolution 36: 1220-1238. Doi:10.1093/molbev/msz060