Research Summary
Our research programme employs basic scientific, clinical and translational methodologies to address fundamental questions related to diseases pathogenesis, assessment and treatment of connective tissue disease, specifically focusing on the scleroderma spectrum. The laboratory research focuses on understanding basic disease mechanisms in connective tissue disease and fibrosis. This has potential impact far beyond SSc. Five major research areas have emerged: 1. Biomarkers for disease including autoantibody profiles 2. Novel pro-inflammatory and fibrotic mediators 3. The origins of fibroblasts and myofibroblast differentiation 4. Molecular genetics of disease sub-sets 5. Development and study of Pre-clinical models. We have a unique clinical resource consisting of patient sample banks comprising of an ever increasing number of new and serial serum and plasma samples across the disease spectrum. We also have a tissue and cell bank which contains OCT and paraffin embedded tissue samples (skin, lung, Kidney) and frozen paired fibroblast cell lines (from lesional and non-lesional sites), and control fibroblast lines. Our genetic studies are supported by a nucleic acid bank which houses genomic DNA and RNA from over 4,000 patients within the disease spectrum. Our candidate gene approach links to gene and protein expression profiling analysis using microarrays, SNP genechips and proteomics. We have also utilised and developed a number of pre-clinical models for scleroderma. These include both inflammatory and non-inflammatory driven animal models of connective tissue scarring and fibrosis affecting the skin, heart, lungs, muscle, and kidney. These pre-clinical models in addition to primary cultures of leukocyte populations and fibroblasts have proved invaluable for the assessment of anti-inflammatory, immuno-modulators and anti-fibrotic compounds prior to their use in clinical trials.