Supervisor View Full Details

• infectious disease and the immune system

• Medicine

• Rheumatology

UCD Centre for Arthritis is a EULAR Centre of Research Excellence, in which we have developed a research focus on inflammatory rheumatic disease, namely arthritis. We work closely with our patients, scientists and clinical staff to provide a multidisciplinary approach to translational research to examine the pathogenic mechanisms involved in disease initiation, progression and outcome. In a systematic clinical programme, based in the UCD CRC, clinical and demographic data is collected and stored securely. In addition, we use routine and experimental biomarkers to stratify patients at disease presentation into disease pathotypes. We collect biosamples including blood, urine, synovial fluid and tissue to obtain cells, DNA, RNA and protein from all relevant compartments. The main aims are to i). identify novel biomarkers of diagnosis and prognosis; ii). discover predictors of therapeutic response; iii). identify novel molecular pathways involved in rheumatic diseases; and v). to develop new therapies.
In the laboratory we use several arthritis models using human tissue from patient with inflammatory arthritis: in-situ, in-vitro and ex-vivo in addition, we have a strong clinical research programme and we have developed some novel in-vivo models also.
The specific research themes are: (i) synovial tissue inflammation; (ii) angiogenesis and invasion of inflammatory cells; (iii) cytokine biology and signalling. We have developed the capability of high-throughput ?omic? analysis in conjunction with computational systems biology to fulfil our stated aims, as above. Finally, as a translational centre we have developed a strong track record in proof of concept clinical trials and we have excellent collaborations with the biopharma industry to study novel therapeutics.

TITLE: PERSONALISED APPROACH TO DIAGNOSIS, PROGNOSIS AND MANAGEMENT OF EROSIVE RHEUMATOID ARTHRITIS
PI: Prof Douglas Veale, UCD

Rheumatoid arthritis (RA) is a chronic autoimmune disease causing joint destruction and disability. Autoantibodies against citrullinated proteins (ACPA) are among the strongest risk factors for bone destruction. ACPA can be present many years before disease onset, suggesting that autoimmunity precedes inflammation and a direct link between autoantibody response and structural bone damage in RA. We therefore hypothesize that ACPA directly influence bone metabolism. Moreover, activation of the adaptive immune system has also been shown to be associated with ACPA positivity and implicated in bone destruction.
In this study we propose to improve the early diagnosis and prognostication of RA patients, by examining the effect of ACPA positivity on synovial invasion and bone destruction. Specifically we will (i) determine the synovial tissue immune cell profile in ACPA+ vs ACPA- RA patients in relation to erosive status, with a particular emphasis on synovial B-cell and http://www.molecularmedicineireland.ie/wellcome-hrb-irish-clinical-academic-training-icat/T-cell populations, (ii) transcriptional profiling to identify biomarkers in an at-risk RA cohort who are ACPA+ with arthralgia with no sign of synovitis compared to ACPA+ with established disease and (iii) examine the functional role of ACPA on the regulation of synovial cell activation and bone resorption in RA models (in-vitro/ex-vivo). The results of these studies will provide insight into the diagnosis and prognosis of patients with RA at an earlier stage of disease than is currently possible and may allow correct treatment at onset of disease or before. The impact of this on patient-care, efficiency and cost effectiveness in our healthcare system will be significant.