Dr Seamas Donnelly's research work epitomises our translational research focus where original bench-based observations are translated to clinical disease. In particular his group defines key regulatory mechanisms which drive aberrant remodelling and repair and predispose towards chronic inflammatory diseases. 

They are particularly interested in:

• Development of novel anti-inflammatory small molecular weight therapies
• Host environmental influences on the regulation of the inflammatory response.
• Genetic profiling guiding disease diagnosis, prognosis and response to therapy
• Host/Pathogen interactions which predispose towards more aggressive infection.

The research team utilise advanced cell and molecular biology techniques, in vitro cell and in vivo animal models to address these questions. It is hoped that their work will pave the way for specific tailored therapies which would attenuate key regulatory pathways that drive chronic inflammatory disease.

Work in Professor Catherine Godson's laboratory focuses on understanding signal transduction processes implicated in disease states such as inflammation and diabetes. They are particularly interested in understanding the mechanisms underlying the resolution of inflammation. It is increasingly appreciated that the resolution of inflammation is a dynamically regulated process. Whereas inflammation is appropriate to effective host defence, in several chronic disease including the arthritides, atherosclerosis and colitis, chronic inflammation persists contributing to the pathology of these conditions. The resolution of inflammation does not merely reflect the dissipation of proinflammatory signals but the active generation of anti-inflammatory mediators, which included the lipoxins.

Research within Prof Godson's team includes investigations into:

• Microvascular complications of diabetes and TGF-β signalling networks
• Mammalian cell signal transduction
• The resolution of inflammatory responses 

Synovial macrophages are one of the resident cell types in synovial tissue and while they remain relatively quiescent in the healthy joint, they become activated in the inflamed joint and, along with infiltrating monocytes/macrophages, regulate secretion of pro-inflammatory cytokines and enzymes involved in driving the inflammatory response and joint destruction.  Synovial macrophages are positioned throughout the sub-lining layer and lining layer at the cartilage–pannus junction and mediate articular destruction. Sub-lining macrophages are now also considered as the most reliable biomarker for disease severity and response to therapy in rheumatoid arthritis (RA).

There is a growing understanding of the molecular drivers of inflammation and an appreciation that the resolution of inflammation is an active process rather than a passive return to homeostasis, and this has implications for our understanding of the role of macrophages in inflammation. Macrophage phenotype determines the cytokine secretion profile and tissue destruction capabilities of these cells. Whereas inflammatory synovial macrophages have not yet been classified into one phenotype or another it is widely known that TNFα and IL-l, characteristically released by M1 macrophages, are abundant in RA while IL-10 activity, characteristic of M2 macrophages, is somewhat diminished.

Professor Catherine Godson and her research group are investigating macrophages and macrophage polarization in RA as well as the elements implicated in controlling polarization, such as cytokines and transcription factors like NFκB, IRFs and NR4A, and pro-resolving factors, such as LXA4 and other lipid mediators which may promote a non-inflammatory, pro-resolving phenotype, and may represent a novel therapeutic paradigm.

Ref.: Frontier in Immunol. 2011; 2: 52.