Steadman, Robert - Cardiff University

个人简介

Education/Qualifications 1989, PhD; University of Wales, Cardiff. 1986, MSc; University of Birmingham, Birmingham 1978, BSc; University of Wales, Aberystwyth Career overview 1993-1997 Lecturer in Cell Biology, Institute of Nephrology, University of Wales College of Medicine, Royal Infirmary, Cardiff, UK 1992-1993 Postdoctoral Research Fellow, Institute of Nephrology, University of Wales College of Medicine, Royal Infirmary, Cardiff, UK 1990-1992 Visiting Senior Fullbright Scholar, Department of Cell Biology and Anatomy, University of Alabama at Birmingham, Alabama, USA.

研究领域

The research of my group focuses on understanding the common mechanisms controlling the processes of wound healing, scarring and fibrosis. These all centre on the induction and function of the myofibroblast. This cell is not present in normal tissue but differentiates either from endogenous cells, such as fibroblasts or epithelial cells or from circulating fibrocytes that are targeted to sites of tissue remodelling. This differentiation is under the influence of growth factors such as transforming growth factor (TGF)b1 and this is central to the pathological process. Fibroblasts are cells that populate the connective tissue of most organs of the body. When they take up a myofibroblast phenotype they lose their spindle-shaped morphology and become large contractile cells. They develop intracellular actin stress fibres that incorporate a-smooth muscle actin (a-sma) and allow the cell to contract, closing the wound or pulling scar-tissue together. This process is essential to healing skin wounds but pathological when it happens in a solid organ such as the kidney, lungs or liver. Our current focus on the glycosaminoglycan hyaluronan began with the observation that hyaluronan was incorporated into large pericellular matrices when a fibroblast differentiated into a myofibroblast (Jenkins et al JBC, 2004). Delineating the mechanisms regulating this and assigning a role to this matrix has revealed that there is a causal relationship between hyaluronan assembly and cell phenotype . We are now at the point where we’re beginning to understand some of the factors that are involved in controlling the hyaluronan-dependent regulation of cell phenotype and have begun to fill the mechanistic gaps in our understanding.

近期论文

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Martin, J.et al. 2016. Tumour necrosis factor-stimulated gene (TSG)-6-mediated interactions with the inter-alpha-inhibitor heavy chain 5 facilitate TGF beta1-dependent fibroblast to myofibroblast differentiation.. Journal of Biological Chemistry 291(26), pp. 13789-13801. (10.1074/jbc.M115.670521) pdf Midgley, A.et al. 2016. 17{beta}-estradiol ameliorates age-associated loss of ﬁbroblast function by attenuating IFN-{gamma}/STAT1-dependent miR-7 upregulation. Aging Cell 15(3), pp. 531-541. (10.1111/acel.12462) pdf Meran, S.et al. 2015. Hyaluronan regulates bone morphogenetic protein-7-dependent prevention and reversal of myofibroblast phenotype. The Journal of Biological Chemistry 129, pp. 11218-11234. (10.1074/jbc.M114.625939) pdf Webber, J.et al. 2015. Differentiation of tumour-promoting stromal myofibroblasts by cancer exosomes. Oncogene 34, pp. 290-302. (10.1038/onc.2013.560) pdf Midgley, A.et al. 2014. MicroRNA-7 inhibition rescues age-associated loss of epidermal growth factor receptor and hyaluronan-dependent differentiation in fibroblasts. Aging Cell 13(2), pp. 235-244. (10.1111/acel.12167) Meran, S.et al. 2013. Interleukin-1β induces hyaluronan and CD44-dependent cell protrusions that facilitate fibroblast-monocyte binding. American Journal of Pathology 182(6), pp. 2223-2240. (10.1016/j.ajpath.2013.02.038) Midgley, A.et al. 2013. Transforming growth factor-β1 (TGF-β1)-stimulated fibroblast to myofibroblast differentiation Is mediated by hyaluronan (HA)-facilitated epidermal growth factor receptor (EGFR) and CD44 co-localization in lipid rafts. Journal of Biological Chemistry 288(21), pp. 14824-14838. (10.1074/jbc.M113.451336) Bommayya, G.et al. 2011. Tumour necrosis factor-stimulated gene (TSG)-6 controls epithelial–mesenchymal transition of proximal tubular epithelial cells. International Journal of Biochemistry & Cell Biology 43(12), pp. 1739-1746. (10.1016/j.biocel.2011.08.009) Meran, S.et al. 2011. Hyaluronan facilitates transforming growth factor-β1-dependent proliferation via CD44 and epidermal growth factor receptor interaction. Journal of Biological Chemistry 286(20), pp. 17618-17630. (10.1074/jbc.M111.226563) Khammas, H.et al. 2011. Characterisation of the human ADAM15 promoter. Nephron Experimental Nephrology 118(2), pp. e27-e38. (10.1159/000320698) Meran, S. and Steadman, R. 2011. Fibroblasts and myofibroblasts in renal fibrosis. International Journal of Experimental Pathology 92(3), pp. 158-167. (10.1111/j.1365-2613.2011.00764.x) Webber, J.et al. 2010. Cancer exosomes trigger fibroblast to myofibroblast differentiation. Cancer Research 70(23), pp. 9621-9630. (10.1158/0008-5472.CAN-10-1722)