DrFionaWatt

My work has focussed on the discovery of novel markers of the acute joint injury response, and whether these can help us to predict so-called 'post-traumatic osteoarthritis', the arthritis which can follow joint injury. We have mainly studied cellular markers of inflammation (initially identified as potential candidates in the laboratory) in humans. Measuring biomarkers and other features in synovial fluid (the viscous fluid in joints) appears to be a useful 'window' on the joint. We also have experience working with urine, plasma and serum. Our approach has traditionally focussed on accurate quantitative protein measurement, via immunoassay including MSD, but also other proteomic approaches too. Our other biomarker work includes activity on whole blood RNA and DNA, and an emphasis on combining these various biomarkers with other important clinical features which predict outcome to strengthen clinically useful prognostic models.

Our work focusses on combining predictive factors, be they clinical features or biomarkers into predictive models which are useful in the clinic. This might be in the longer term helping to select an appropriate treatment for an individual, or in the shorter term selecting which patients might be recruited to a clinical trial.

Improving our understanding of the role of individual genetic factors in the prediction of risk is a focus of our recent work. This is particularly important for understanding the development of post-traumatic osteoarthritis and whether known 'osteoarthritis' genetic variants play a role in the evolution of disease following joint injury or other, yet to be defined genes. This work relies on coordinated work with collaborators across three international consortia: OSKGAR, GO and STEp UP OA as well as our work in UK Biobank.

Our work has focussed on following individuals at risk of disease as part of their participation in longitudinal cohort studies, with the aim of understanding more about the clinical and biological predictors of disease progression and trajectories over time - this has included individuals at the time of knee injury (KICK), those who have experienced a symptomatic degenerative meniscal tear (MenTOR) and those who have developed hand osteoarthritis (HOPE cohort). All of these studies collect detailed clinical assessments and outcomes but also imaging and biological samples and measurements with the aim of combining these different types of data to better understand mechanisms and predictors of disease.

Our studies in this area seek to join together our work understanding disease and clinical trials - often asking 'proof of concept' questions in small human studies which give us information on whether a new test or potential new treatment is likely to be feasible. This may be by measuring a molecular marker to test its ability to stratify individuals, or measuring a molecular outcome to test the viability of a potential drug target. This approach aims to improve the success of trials of new treatments for this disease and provide biological justification for proceeding to larger clinical trials.

Our activity in this area has focussed on knee osteoarthritis and hand osteoarthritis. These are largely academically led, often in earlier phase or feasibility studies. A recent example is the NIHR funded HOPE-e - a feasibility randomised controlled trial studying a form of hormone replacement therapy in post-menopausal women with symptomatic osteoarthritis of the hand. This study has been run in collaboration with Oxford Clinical Trials Unit (OCTRU). We have also collaborated on larger multi-centre academically led clinical trials in osteoarthritis (HERO, PROMOTE) and some commercially sponsored studies where targets are of shared academic interest (OAK, TANGO).