Advancing pharmacological approaches for resolving inflammation
Inflammation is central to the damage caused by ischaemia-reperfusion injury (I/RI), a condition underlying numerous illnesses including: myocardial infarction, stroke, kidney disease, solid organ transplantation, sepsis, and inflammatory bowel disease. This pathological cascade, exacerbated by endothelial cell activation, pro-inflammatory mediator release, and the recruitment of leukocytes (especially neutrophils) and platelets, contributes to microvascular dysfunction and tissue injury. In the brain, these effects are particularly severe, as seen in ischaemic stroke, a leading global cause of death and disability. While early reperfusion is vital, it often triggers inflammatory events that exacerbate the initial damage.
Our research focuses on the active, orchestrated process of inflammation resolution, which involves mediators such as Annexin A1 (AnxA1), resolvins, and protectins, as well as the Formyl Peptide Receptor 2/Lipoxin A4 receptor (FPR2/ALX) pathway. Disruption of these pathways in chronic inflammatory conditions prolongs inflammation and worsens tissue damage. We have demonstrated a critical protective role for FPR2/ALX, positioning it as a promising therapeutic target for I/RI.
Our primary aim within this research is to generate transformative data to address scientific and clinical gaps. Our goals include characterising pathophysiological responses to I/RI across various diseases, identifying prognostic biomarkers, and developing pharmacological strategies to activate resolution pathways. We are testing AnxA1-based biologics, such as native N-term 2-50, which selectively act via FPR2/ALX to reduce inflammation and brain damage in ischaemic stroke.
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By advancing resolution biology and FPR2/ALX-targeting therapies, our work aims to advance the field of drug discovery, addressing the global burden of stroke and inflammation-driven diseases to improve patient outcomes and pioneer innovative treatments.
This work is funded by:
