Project title: Functional characterisation of inflammation and vascular remodelling pathways in GCA
Rationale:Pathways identified with multi-omics approaches need to be functionally validated and pre-clinically interrogated with new targeted therapies
Objectives:Establish co-culture systems from ex-vivo vascular tissue, and culture of temporal artery biopsies in 3D matrix. In vitro drug target manipulation as informed by genetic and transcriptomic analyses, using readouts such as changes in infiltrating cell subsets, proliferation and apoptosis, T-cell differentiation pathways, protease / reactive oxygen species release and myointimal cell proliferation (Objective 7). Stained specimens will be analysed using TG machine learning algorithms and potential biomarkers identified in these assays validated in samples from ESR8/9 patient cohorts.
Expected Results:These functional models will contribute to pathway discovery and application of machine learning-supported tissue analysis will provide a new tissue analysis approach. Vascular inflammation and vascular remodelling stratification tools may be discovered and validated in patient cohorts
Planned Secondments:CSIC: 2 mths (alignment genetics to pathological derangement); TG: 2 mths (tissue morphometry on stained GCA sections)