The actin cytoskeleton regulates many cellular processes, primarily by providing the mechanical forces necessary for cellular shape change and therefore is essential for cell migration and invasion, both critical determinants during development and disease.
We propose to study cell migration in its 'native' environment, i.e. in a live animal, to improve the understanding of its underlying mechanisms. In particular, we will disturb actin contractility and the cytokine environment in a controlled manner. We will then investigate the effects using whole-body imaging to track the cells in vivo and metabolomics to determine cellular changes.
Sanz-Moreno V, Gaggioli, C, Yeo M Albrengues J. Wallberg F, Viros A , Hooper S, Mitter R, Feral C, Cook M; Larkin J , Marais R , Meneguzzi G, Sahai E, Marshall, CJ. "ROCK and JAK1 signalling cooperate to control actomyosin contractility in tumour cells and stroma." (2011) Cancer Cell, 20, 229-45. -Commented in Nat Rev Cancer, 11, 10,690 (2011), in Cancer Discovery, 1,4, 284 (2011), in Nat Cell Biol, 13, 1188 (2011) - Included in the Special issue of “Best of Cancer Cell 2011” selected to be part of the top 20 papers in 2011 - BBC news channel: http://www.bbc.co.uk/news/health-14530143
Sanz-Moreno V , Gadea G, Ahn J, Paterson H, Marra P, Pinner S, Sahai E and Marshall CJ, “Rac activation and inactivation control plasticity of tumour cell movement.” (2008) Cell, 135, 510-23. -Commented in Nat Rev Cancer, 9, 1, 3(2008), in Cancer Cell, 14, 5 (2008), in Pigment Cell and Melanoma Research, 22, 148-9 (2008), in Medicinal Sciences, 25, 4, 343-5 (2008) - BBC news channel: http://news.bbc.co.uk/1/hi/health/7700264.stm
Fruhwirth GO, Diocou S, Blower PJ, Mullen G, Ng T "A whole-body dual-modality radionuclide optical strategy for preclinical imaging of metastasis and heterogeneous treatment response in different microenvironments." (2014) J Nuc Med 55(4):686-94.
Vermeer LS, Fruhwirth GO, Pandya P, Ng T, Mason AJ, "NMR metabolomics of MTLn3E breast cancer cells identifies a role for CXCR4 in lipid and choline regulation." (2012) J Proteome Res 11: 2996-3003.