Joe Boyle

Summary

Joseph Boyle is a Clinical Reader in Molecular Vascular Pathology in the National Heart and Lung Institute.

Dr Boyle’s research focus is in understanding the gene regulation of macrophages in atherosclerosis.

Dr Boyle's first degree is in Pharmacology (Class I Hons, 1988, plus Prize) from the University of Glasgow. At the University of Glasgow, this comes with a very solid grounding in organic and physical chemistry, laboratory practicals, and integration with world-leading investigators in cell signalling and vascular biology.

Dr Boyle then completed training in Medicine, scoring in the top few in the year (MBChB with Hons, 1991). Work as a junior doctor witnessing fatal cardiovascular disease inspired a career in its pathogenesis. He specialised in Histopathology and then subspecialised in renal and cardiovascular histopathology.

Concurrently, Dr Boyle moved to the University of Cambridge and did a PhD on macrophage biology in atherosclerosis with Professors Peter Weissberg and Martin Bennett and Dr David Bowyer.

In London, Dr Boyle became a BHF Intermediate Clinical Research Fellow with Professor Dorian Haskard. In this work, he defined a novel macrophage pro-resolution phenotype related to intraplaque hemorrhage (Figure) and defined its driving transcription factor, which is Activating Transcription Factor 1 (ATF1) (Figure). ATF1 in turn was activated by Adenosine Monophosphate Activated Kinase (AMPK).

Dr Boyle then became a BHF Senior Clinical Research Fellow to develop mechanistic and translational studies of the AMPK-ATF1-HMOX1-Mhem pathway. He discovered that:

• metformin may suppress atherosclerosis in vivo via macrophage AMPK, rather than via an effect on blood glucose.
• normal resolution of tissue hemorrhage in vivo requires AMPK and ATF1; and their deficiency results in inflammation and oxidative stress. This is likely to apply to any hemorrhage including intraplaque hemorrrhage and intracranial hemorrhage (Figure).

chromatin remodelling mediated by the cardiovascular risk gene SMARCA4 contributes to the specificity of gene activation that distinguishes leukocyte resolution from erythrocyte resolution whilst they use related transcription factor binding sites (Figure).

• In close collaboration with Prof Nick Long and group in Chemistry (Molecular Sciences Research Hub), Dr Boyle has designed and validated a novel fluorescence turn-on break-apart probe specifically for Heme Oxygenase activity. Whilst similar probes have been used with oligonucleotides and oligopeptides, this seems to be a first for a metabolite. This shows promise as a research reagent, and an in vitro diagnostic. It is aimed at development into a clinical diagnostic with certain types of fluorescence imaging.

Much of his current work focusses on chromatin remodelling and epigenetic changes during the response to hemin, and how that compares with responses dung inflammation resolution.

He is fully clinically trained in histopathology, mainly at Cambridge, and specialised in cardiovascular and renal pathology.

Recent awards

• British Atherosclerosis Society John French Lecture
• University of Glasgow Tenovus Lecture
• Multiple international invited seminars.