Roles of the Extracellular Matrix in Cell Motility Processes and Signaling to the Cytoskeleton
The central interest of the laboratory is in cell-matrix adhesion processes and their roles in regulating intracellular signaling and cell protrusions. We study molecular mechanisms of these processes in health and disease. Research areas focus on extracellular processes that modulate extracellular matrix organization, also on intracellular signaling pathways that regulate actin cytoskeletal organisation in cell protrusions and adhesion complexes. More details of each area are given on the laboratory Group Page.
Fascin-based protrusions and their role in carcinoma cell migration and metastasis: Current projects study signaling mechanisms that regulate actin-bundling by fascin-1 in carcinoma cell migration and metastasis, examine how fascin-1 and other components of protrusions are integrated, and assess the clinical relevance and suitability of fascin-1 as a potential novel therapeutic target.
Thrombospondins and their roles in Extracellular Matrix: We are examining the evolution of thrombospondins and their conserved roles within the extracellular matrix, in particular the molecular mechanisms by which thrombospondins accumulate in the extracellular matrix through interactions with cell surfaces and other matrix components.
The Muskelin/RanBP9/CTLH complex: Muskelin and RanBP9 are co-associated proteins whose knockdown phenotypes in mammalian cells demonstrate functional roles in cell morphology regulation. RanBP9 mediates association with a widely-expressed protein complex, referred to as muskelin/RanBP9/CTLH complex. A homologous complex in budding yeast functions in proteosomal and vacuolar degradation of specific target proteins, however, fundamental aspects of the organisation, regulation and roles of muskelin/RanBP9/CTLH complex in mammalian cells remain unknown. We are examining the hypothesis that mammalian muskelin/RanBP9/CTLH complex regulates degradation of specific target proteins that include cytoskeletal and adhesion proteins.
Elena Christofidou, Ore Francis, and Vanessa Tan.
Jayo A, Parsons M, Adams JC. (2012) A novel Rho-dependent pathway that drives interaction of fascin-1 with LIM kinase1/2 to promote fascin-1/actin binding and filopodia stability. BMC Biology. 10(1):72.
Mosher DF, Adams JC. (2012) Adhesion-modulating/matricellular ECM protein families: a structural, functional and evolutionary appraisal. Matrix Biology. 31:155-161.
Hashimoto Y, Loftis DW, Adams JC. (2009) Fascin-1 promoter activity is regulated by CREB and the aryl hydrocarbon receptor in human carcinoma cells. PLoS ONE. 4(4):e5130.
Adams, JC, Bentley, AA, Kvansakul M, Hatherley D, Hohenester E. (2008). Extracellular matrix retention of thrombospondin-1 is controlled by its conserved C-terminal region. Journal of Cell Science. 121: 784-795.