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Full NameDr Ronan Mullan
Department:Department of Rheumatology
Organisation:Trinity College Dublin
- genetics, genomics and molecular biology
- infectious disease and the immune system
- physiology and non-communicable disease
Postgrad Medical Specialties
- Clinical Trials
The Academic Department of Rheumatology in Tallaght Hospital has an active research program which is well suited to the pursuit of academic medical PhD projects. We are engaged in an ongoing HRB-funded program investigating the mechanisms of immune-metabolism in inflammatory arthritis, and have an established programme of ongoing musculoskeletal ultrasound research.
The department’s clinical facilities include a bone and joint unit containing a dedicated rheumatology procedure suite for synovial biopsy & tissue sampling, and a state-of-the-art suite of ultrasound equipment used both for daily clinical practice and research purposes. For our translational research work, we routinely collect and store synovial tissue, synovial fluid and peripheral blood cells, DNA and RNA samples taken from patients with inflammatory arthritis. We have an on-site research tissue culture and wet-lab facility. Our medical researchers are supported by an on-site laboratory manager, a post-doctoral scientist and through collaborative partnerships with Rheumatology and Immunology researchers based at the Trinity Biological Sciences Institute, Trinity College Dublin and beyond.
The Identification of Therapeutic Metabolic Strategies of in the Treatment of Inflammatory Arthritis
PI: Dr Ronan Mullan
All forms of inflammatory arthritis are characterised by altered glucose metabolism & insulin resistance, leading over time to increased cardiovascular disease, sarcopenia, and Type II diabetes. We have shown that metformin, an oral biguanide used for the treatment of Type II Diabetes, reduces pro-inflammatory responses in Rheumatoid Arthritis Synovial Fibroblast cells and ameliorates in-vitro models of inflammatory arthritis.
In the proposed research project, the successful PhD candidate will further enrich a cohort of patients with inflammatory arthritis and will co-ordinate tissue sampling to further their own supported translational research programme within the Department. Relationships between arthritis disease activity, insulin resistance & biomarkers of metabolism will be assessed. Measures of endothelial and cardiovascular function using vascular ultrasound imaging will also be performed.
In a sub-group of patients, synovial tissue biopsies, peripheral blood mononuclear cells and where possible synovial fluid mononuclear cells will be sampled both prior to, and 3-months following initiation of biological therapy. Relationships between arthritis treatment response and changes to parameters of glucose metabolism, insulin resistance and cardiovascular function will be assessed. At a tissue/cellular level using a variety of techniques including immunohistochemistry, protein assays, and bio-assays performed on patient-derived synovial fibroblast cell lines, primary endothelial cell lines and explant cultures, the effects of targeted manipulation of glucose metabolism by compounds including but not exclusive to metformin and the AMPK activator AICAR will be assessed.
The result of this work will provide new insights into the management of patients with inflammatory arthritis with the potential to lead to new treatment strategies in the management of these and other inflammatory diseases.