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Professor John Greenwood is the Hugh Davson Professor of Biomedical Research and Head of the Department of Cell Biology at the UCL Institute of Ophthalmology, University College London.
The research staff occupy state-of-the-art laboratories in the Henry
Wellcome Building for Translational Eye Research at the UCL Institute of
Ophthalmology. This new building was the result a successful £9.2M
application led by Greenwood and funded by the Wellcome Trust and Fight
for Sight.
Research
Research into the role the vascular endothelium plays in the pathogenesis of retinal and brain inflammation is a core component of the laboratory. A significant part of this research addresses the role the vascular endothelium plays in inflammation. Such work has been at the forefront of identifying and characterising novel endothelial cell mechanisms that facilitate the recruitment of leukocytes to the retina and brain, a critical step in the pathogenesis of diseases such as multiple sclerosis and posterior uveitis.
This work has established the principle of outside-in signalling in CNS endothelial cells mediated through leukocyte engagement of endothelial cell adhesion molecules and the downstream effector mechanisms that support leucocyte transvascular migration. With this information we have been able to design novel therapeutic approaches to target these critical pathways in order to reduce leukocyte recruitment and attenuation the disease process. Work from the Greenwood laboratory has influenced the decision to trial statin therapy for the treatment of multiple sclerosis.
Selected bibliography (since 2001):
Chataway, J., Scheurer, N., Alsanousi, A., Chan, D., MacManus, D., Hunter, K., Anderson, V., Foster, J., Bangham, C., Clegg, S., Nielsen, C., Fox, N.C., Wilkie, D., Nicholas, J.M., Calder, V., Greenwood, J., Frost, C., Nicholas, R. (2013). High dose simvastatin slows brain atrophy and disability in secondary progressive multiple sclerosis: a phase 2 placebo-controlled trial (MS-STAT). The Lancet (ahead of print).
Martinelli, R., Newton, G., Carman, C.V., Greenwood, J. and Luscinskas, F.W. (2013). Novel role of CD47 in rat microvascular endothelium: signaling and regulation of T cell transendothelial migration. Arterioscler Throm Vasc Biol. 33:2566-2576.
Wang, X., Abraham, S., McKenzie, J.A.G., Jeffs, N., Swire, M., Tripathi, V.B., Luhmann, U.F.O., Lange, C.A.K., Zhai, Z., Arthur, H.M., Bainbridge, J., Moss, S.E. and Greenwood, J. (2013). LRG1 promotes angiogenesis by modulating endothelial TGFß signalling. Nature 499: 306-311.
Martins, T., Burgoyne, T., Hudson, N., Ambrósio, A.F., Silva, A.P., Futter, C.E., Greenwood, J. and Turowski, P. (2013). Methamphetamine-induced nitric oxide promotes vesicular transport in blood-brain barrier endothelial cells. Neuropharmacol. 65: 74-82.
McKenzie, J.A., Fruttiger, M., Abraham, S., Lange, C., Stone, J., Gandhi, P., Wang, X., Bainbridge, J., Moss, S.E. and Greenwood, J. (2012). Apelin is required for non-neovascular remodelling in the retina. Am. J. Pathol. 108:399-409.
Greenwood, J., Heasman, S.J., Alvarez, J.I., Prat, A., Lyck, R. and Engelhardt, B. (2011). Leukocyte-endothelial cell crosstalk at the blood-brain barrier: A prerequisite for successful immune cell entry to the brain. Neuropath. Appl. Neurobiol. 37:24-39.
Martinelli R., Gegg M, Longbottom R., Adamson P, Turowski P. and Greenwood J. (2009). ICAM-1-mediated eNOS activation via calcium and AMPK is required for transendothelial lymphocyte migration. Mol. Biol. Cell 20:995-1005.
Turowski, P., Martinelli, R., Crawford, R., Wateridge, D., Papagiorgiou, A-P., Lampugnani, M.G., Gqamp, A., Vestweber, D., Adamson, P., Dejana, E. and Greenwood, J. (2008). Phosphorylation of vascular endothelial cadherin controls lymphocyte emigration. J. Cell Sci. 121:29-37.
Greenwood, J. and Mason, J.C. (2007). Statins and the vascular endothelial inflammatory response. Trends Immunol. 28: 88-98.
Greenwood, J., Steinman, L. and Zamvil, S.S. (2006). Statin therapy and autoimmune disease: from protein prenylation to immunomodulation. Nat. Rev. Immunol. 6: 358-370.
Gegg, M., Harry, R., Hankey, D., Zambarakji, H., Pryce, G., Baker, D., Adamson, P., Calder, V. and Greenwood, J. (2005). Suppression of autoimmune retinal disease by lovastatin does not require TH2 cytokine induction. J. Immunol. 174:2327-2335.
Lyck, R., Reiss, Y. Gerwin, N., Greenwood, J., Adamson, P. and Engelhardt, B. (2003). T cell interaction with ICAM-1/ICAM-2-double-deficient brain endothelium in vitro: The cytoplasmic tail of endothelial ICAM-1 is necessary for transendothelial migration of T cells. Blood 102: 3675-3683.
Greenwood, J., Amos, C.L., Walters, C.E., Couraud, P-O., Lyck, R., Engelhardt, B. and Adamson, P. (2003). Intracellular domain of brain endothelial ICAM-1 is essential for T-lymphocyte-mediated signalling and migration. J. Immunol. 171:2099-2108.
Greenwood, J., Walters, C.E., Pryce, G., Kanuga, N., Beraud, E., Baker, D., and Adamson, P. (March 5, 2003). Lovastatin inhibits brain endothelial Rho-dependent lymphocyte migration and attenuates experimental autoimmune encephalomyelitis. FASEB J. On line. 10.1096/fj.02-1014fje (17: 905-907).
Walters, C.E., Pryce, G., Hankey, D.J.R., Sebti, S.M., Hamilton, A.D., Baker, D., Greenwood, J. and Adamson, P. (2002). Inhibition of rho GTPases with protein prenyl transferase inhibitors prevents leukocyte recruitment to the CNS and attenuates clinical signs of disease in an animal model of multiple sclerosis. J. Immunol. 168:4087-4094.