Patrick .J. Tighe
University of Nottingham
UK
Title: Pathway-Centric analysis of rare autoinflammatory diseases (AID) and drug repurposing
Biography
Biography: Patrick .J. Tighe
Abstract
The rare hereditary autoinflammatory periodic syndromes are the result of specific mutations in a range of genes ultimately affecting innate immune response mechanisms, yielding a pro inflammatory state. Despite single genes being causative, the inflammatory consequences are widespread. To better understand the underlying mechanisms associated with TNF receptor-associated Periodic syndrome (TRAPS), as a prototypic model of an AID, we have undertaken extensive examinations of intracellular signalling pathways and cytokines associated with inflammatory responses in such patients, and then applied this roadmap of a perturbed, generally overactive signalling network to seek existing pharmacological drugs which can suppress one or more of the affected pathways, with the goal of repurposing existing drugs for the benefit of TRAPS patients. Several classes of small molecule compound have been identified which show potential benefits, and further classes of small compounds have been derived from in-silico structure and functional comparisons to existing chemical library data.
