Small molecule discovery for inhibition of the GEF-H1/RhoA pathway

Edith Chan (primary)
Medicine
University College London
Maria Balda (secondary)
Institute of Ophthalmology
University College London

Abstract

Chronic inflammation and infection of different tissues results in cell and tissue dysfunction. Identification of molecular targets that are components of signalling pathways that drive inflammation can lead to the development of new therapeutic strategies based on inhibitors that block such signalling components. We have identified the RhoA activator GEF-H1 as a signalling protein that controls paracellular permeability and cell proliferation and drives pathological responses in epithelial and endothelial cells. We will design and validate small molecule inhibitors of the binding of GEF-H1 to RhoA. The inhibitors will allow us to augment our functional studies to test the hypothesis that blockade of the GEF-H1/RhoA pathway can arrest inflammation.


References

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BBSRC Area
Molecules, cells and industrial biotechnology
Area of Biology
Cell BiologyChemical Biology
Techniques & Approaches
BioinformaticsChemistryMolecular BiologySimulation / Modelling