ANNUAL REVIEW master Final3a - St Vincent's University Hospital

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St. Vincent’s Healthcare Group Limited - Annual Review 2007 Education & Research psoriatic arthritis (PsA) synovial tissue correlates with change in DAS28 following initiation of biologic therapy. Finally Eliza is examining the role of TLRs in patients with PsA. Eliza has demonstrated expression of TLR-2/4 in the endothelial and lining layer regions of the synovium. Currently she is stimulating primary fibroblasts from patients with PsA with TLR-2 and 4 +/- cJun inhibitors and assessing regulation of chemokines. (3) Psoriasis/Psoriatic Arthritis (i) Biomarkers of Biologic Treatment Response: As part of investigator-originated lead by Prof FitzGerald, single-arm protocols looking at mechanisms of effect of biologic therapies, 6mm skin biopsy (uninvolved at baseline only; leading edge of Ps lesion at baseline and follow-up) and synovial membrane (obtained under local-anaesthetic at mini-arthroscopy pre-and post-biologic therapy) samples are available for study following infliximab (n=15), IL-1Ra (n=12) and etanercept (n=15,). Comparisons of immunohistochemical (IH) changes will be made with standard clinical measures and with MRI changes in the affected knee joint. The IH and semi-quantitative MRI (collaboration with Dr. Robin Gibney) analysis has now been completed and comparisons are being made with clinical response markers. In addition, with Prof Patrick Brennan’s group from Imaging UCD, a more quantitative measure of synovitis is being developed. Finally, funded by Abbott, a new post doctoral scientist has been appointed who will be analysing differential protein expression in these patientderived samples together with Prof Steve Pennington from UCD. (ii) Expression and Regulation of Transcription factors in Ps/PsA: This work is lead by Dr. Evelyn Murphy and Dr. Brian Kirby, the expression and regulation of NURR proteins pre-and post-treatment is being explored. Findings have established the aberrant expression and distribution of the orphan nuclear receptor NURR1 in psoriasis and suggest that clinical benefits of TNF-α inhibition may be mediated through altered NURR1 activity. In addition, a recent paper suggests a key regulatory role for the AP-1 transcription complex in Ps/PsA. (iii) T cell Receptor Phenotype: Following on previous publications in PsA, the observations are currently being extended, in collaboration with Prof Bob Winchester, to ankylosing spondylitis where the patients are carefully HLA-matched. Preliminary results indicate significant clonal expansion within both the CD4 and CD8 populations. (iv) Synovial Proteomics Dr Emily Collins is examining proteomic profiles in PsA patients pre/post biologic therapy. We are aiming to identify molecular biomarkers which predict response to anti-TNF· therapy which are present in the synovium at an early stage of treatment. This project is led by Prof FitzGerald and Dr Ursula Fearon in collaboration with the P.P. Tak group in Amsterdam, and S. Pennington and M. Dunn of the Proteome Research Centre, UCD. Synovial tissue has been obtained via arthroscopy at baseline and 1 month from a cohort of patients, half of whom were receiving Adalimumab and half placebo injections, before beginning Adalimumab after 1 month. We are using proteomics technology (2D- DIGE and mass spectrometry) to analyse the proteome of these synovial tissue samples and identify differentially expressed proteins and potential biomarkers. These potential biomarkers will then be validated using various molecular biology methods. A pilot study on a smaller cohort has allowed us to optimise the experimental methodology and identify several interesting proteins. Return to Contents 28
St. Vincent’s Healthcare Group Limited - Annual Review 2007 Education & Research Student Awards and Oral Presentations: Dr Ronan Mullan; IJMS Awards Best Published Paper – Rheumatology 2007 Research Awards. Mullan RH, Golden Mason L, Markham T, O'Hara R, FitzGerald O, Bresnihan B, Veale DJ, Fearon U. A novel role for Serum Amyloid-A (A-SAA) in Angiogenesis and Adhesion Molecule expression through an NFÎB-dependent signal transduction pathway. Aisling Kennedy; SIAR Award/Oral presentation - American College of Rheumatology Boston 2007. Kennedy A, Ng C, Mc Cormick J, Fearon U, Veale DJ. Oxidative Damage and Hypoxia in Inflammatory Arthritis: Evidence from in vivo and ex vivo studies of Inflammatory Arthritis. Mary Connolly; SIAR Award - American College of Rheumatology, Boston 2007 Mary Connolly, Jennifer McCormick, Ronan Mullan, Barry Bresnihan, Oliver FitzGerald, Douglas Veale, Ursula Fearon. Acute Serum Amyloid A Upregulates TNFα Expression in RA Synovial Tissue Explants & Induces Cell Migrational Processes Mary Connolly: Eular Travel Award– European Rheumatology Meeting, Barcelona 2007. M.C. Connolly, J. McCormick, R. Mullan, O. FitzGerald, B. Bresnihan, D.J. Veale, U. Fearon.Acute serum amyloid a stimulation of RA synovial tissue ex vivo upregulates chemokine expression, TNFα and MMP production via theNFÎB pathway Thesis Submission Dr Ronan Mullan submitted his PhD thesis (UCD) examining the role of A-SAA in the pathogenesis of inflammatory arthritis, under the supervision of Dr Ursula Fearon and Prof Douglas Veale Bioinformatics and Molecular Evolution Principal Investigator: Senior scientists: Graduate student: Professor Cliona O’Farrelly, PhD Andrew T. Lloyd PhD Paul Cormican M.Sc. The FIRM III project, funded by the Department of Agriculture, continues to investigate innate immunity in chickens by characterising the genes mobilised after Campylobacter jejuni infection. We have further developed the bioinformatic discovery pipeline for analysing the frequency of Single Nucleotide Polymorphisms (SNPs) in chickens and classifying SNP-rich genes in its genome. We have made a start at defining the Immunome (those genes that are involved in immunological processes) by comparing the contents of immunological gene lists. The two projects, started in 2006, investigating the response to Campylobacter infection in chickens and the response to the diseases of mastitis and metritis in cattle continue. We were centrally involved in a community project to sort out the nomenclature of avian defensins. Return to Contents 29
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Papers Published & Accepted Ponikow
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Lios Aoibhinn Cancer Support Centre
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Cancer remains a significant focus
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ANNUAL REVIEW master Final3a - St Vincent's University Hospital

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