||Key achievements since 2001||Other||UCL Institute of Ophthalmology|
1) Identification of a novel protein complex and functional analysis of the molecular mechanism by which tight junctions regulate gene expression, cell proliferation and differentiation. 2) Disclosure of genes transcriptionally regulated by the tight junction associated transcription factor ZONAB, such as erbB-2, PCNA and cyclin D1. 3) Discovery of a tight junction-associated guanine nucleotide exchange factor for Rho GTPases, GEF-H1, and functional analysis of its role in the regulation of paracellular permeability and cell proliferation. 4) Identification of tight junction proteins, GEF-H1, as potential targets for the development of novel therapies for proliferative or degenerative eye diseases and tumorigenesis. 5) Discovery and initial functional analysis of a novel transmembrane protein of tight junctions, MarvelD3, and its role in tight junction functions. 6) Identification of novel junction-associated RhoGTPase regulators (p114RhoGEF, SH3BP1, Dbl3 and DLC2). 7) Identification of a new stress response pathway that links Ras-activated Rho signalling to ZONAB-mediated mRNA stabilisation and translation. 8) Disclosure of the role of the tight junction transmembrane protein MarvelD3 in coupling tight junctions to the MEKK1-JNK pathway to regulate cell behavior and survival. 9) Identification of the molecular mechanisms by which the ZO-1 tight junctions associated protein regulates endothelial adherens junctions, cell-cell tension, angiogenesis, and barrier formation. 10) Discovery of the role of MarvelD3 during early Xenopus development and eye formation. 11) Disclosure of the essential role of p114RhoGEF for mouse development.