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Promoting inflammation resolution in sickle cell disease

Targeting Formyl Peptide Receptors to Promote Resolution Following Cerebral Ischaemia/Reperfusion Injury in Sickle Cell Disease

Ischaemic stroke is a leading cause of death and disability, with inflammation crucially involved in AIS pathophysiology. During ischaemic stroke, blood supply to parts of the brain becomes limited causing cell death. This complex response involves blood vessels, chemical mediators and immune cells (termed “inflammation”). Ongoing or worsening inflammation further damages the brain. Reducing, and ideally eliminating inflammation is critical to recovery from stroke – a process termed ‘resolution’. The ideal outcome of inflammation is its resolution, which is a tightly orchestrated process. We are particularly interested in one key player of resolution, the formyl peptide receptor 2 (Fpr2/ALX), which is found on certain immune cells. In mice, targeting Fpr2/ALX limits brain damage during stroke.

This project focuses on an in vivo model of stroke that is coupled to a chronic inflammatory condition: Sickle Cell Disease (SCD), a disorder affecting red blood cells. People with SCD have chronic inflammation throughout their bodies and are at high-risk of ischaemic stroke. We are investigating whether targeting the Fpr2/ALX, which resolves inflammation, can limit brain damage during SCD-associated stroke. To test this hypothesis, we are initiating stroke in SCD mice to study its extent in the presence of drugs affecting Fpr2/ALX.

The potential impact of this research project is far reaching. It will provide insight into the pathophysiology of stroke, discovering novel ways to promote resolution of inflammation post stroke in SCD.

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Meet the Principal Investigator(s) for the project

Professor Felicity Gavins
Professor Felicity Gavins - Felicity read Pharmacology at the University of Sunderland, where she also embarked on an industrial placement year at Bayer Pharmaceuticals in Slough. After completing her BSc (Hons), she moved to London to study for a Ph.D. in Pharmacology at Queen Mary University London, supported by the British Heart Foundation (BHF). Felicity was then awarded a BHF Junior Research Fellowship to undertake further research both in the UK and the USA. In 2007 Felicity joined Imperial College London to take up a Lectureship position in the Centre for Integrative Mammalian Physiology and Pharmacology (CIMPP). This was shortly followed by a senior lectureship and the appointment to Deputy Head of The Centre of Neurodegeneration & Neuroinflammation. In 2013 she accepted an academic position in the USA at Louisiana State University Health Sciences Center-Shreveport (LSUHSC-S) and was appointed Director of The Small Animal Imaging Facility. Felicity is a Fellow of the British Pharmacological Society and of the Royal Society of Biology. She joined Brunel University London in August 2019 as Professor of Pharmacology and Royal Society Wolfson Fellow, and is the Director of The Centre for Inflammation Research and Translational Medicine (CIRTM). Throughout her academic career, Felicity has worked with and served on numerous national and international research councils, medical charities and learned societies. She has published widely in her field and received a number of awards and honours for her work. She has received funding for her research from a range of funders including: the Royal Society and the Wolfson Foundation (RSWF), the British Heart Foundation (BHF), the Medical Research Council (MRC), the Biotechnology and Biological Sciences Research Council (BBSRC), the American Heart Association (AHA), and the National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI). Felicity continues to be actively involved in public and patient organizations which has been immensely instructive for her research. She is also dedicated to promoting mentoring and collaborative research, along with facilitating mentoring of post-doctoral fellows/early-career investigators.

Related Research Group(s)

human body

Inflammation Research and Translational Medicine - Driving scientific innovation and discovery for diagnosis, treatment, and management of cardiovascular disease, inflammatory and immune disorders, microbial resistance, and cancer.

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Project last modified 29/09/2023