Major research interests of the centre focus on understanding the molecular and cell biology of connective tissue diseases, including tissue repair and remodeling processes, degenerative joint disease (osteoarthritis), and the genetic and molecular mechanisms underlying tissue scarring and replacement fibrosis (scleroderma). We pioneered the development and use of in vivo systems of human disease (transgenic and genetically modified conventional and conditional knock-out mice) as pre-clinical models to investigate disease pathogenesis and also discovery and validation programmes.
Our research programme uses tissue biopsies and in vitro systems to investigate critical mechanisms of disease pathogenesis, utilising control and patient-derived tissues and cells and in vivo models. Key regulatory pathways are examined, leading to a better understanding of disease pathogenesis, and improved management and treatment of connective tissue diseases.
The Centre uses a translational approach to biomedical research. Basic science discoveries lead to large clinical programmes in scleroderma at the Royal Free Hospital, where a team-based environment co-ordinates multidisciplinary care for more than 1500 patients. The Centre also contains large specialist pulmonary hypertension (PAH) and Raynaud's phenomenon (RP) clinics incorporated within the connective tissue diseases service.
Major research areas include:
- Genetics of the connective tissue disease scleroderma
- Vascular biology and pulmonary hypertension
- Autoimmune and immune activation
- Extracellular matrix biology leading to scarring and fibrosis in scleroderma
- Pathogenesis of degenerative joint disease
- Development of in vivo pre-clinical models of connective tissue disease
Areas of interest for our research groups:
Professor Chris Denton
Research focuses on studies relevant to systemic sclerosis (scleroderma) and related connective tissue disease and spans clinical, translational and basic scientific themes. Clinical projects include interventional clinical trials in the area of scleroderma, Raynaud's phenomenon and pulmonary hypertension as well as research examining predictors of outcome and stratified approaches to patient investigation and management. Translational projects include studies of systemic sclerosis biology and development of new in vitro and in vivo model systems to test hypotheses of pathogenesis and new targets for therapy. The group has close links with others in the centre working on fibrosis, vascular biology and genetics.
Dr Markella Ponticos
Research interests include the mechanisms that underpin the biology of mesenchymal cells in normal tissues (skin, lungs and vessels) and the way they alter during wound healing, tissue remodelling and in disease. Interest lies in the transcriptional control mechanism(s) that result in the regulation of extracellular matrix genes in vivo, with particular emphasis on the fibroblast / myofibroblast and the smooth muscle cell. There are three main linked areas of study: (1) Vascular remodelling in atherosclerosis and pulmonary arterial hypertension (2) Biology of mesenchymal cells and the cell and molecular mechanism(s) of tissue repair, scarring and fibrosis (3) Tissue specific regulation of genes to define mesenchymal cell lineages using Collagen Type I gene regulation.