Joseph Boyle is a British Heart Foundation Senior Clinical Research Fellow in the Vascular Sciences section, National Heart and Lung Institute.
Dr Boyle qualified in Pharmacology (Class I Hons, 1988) and Medicine (with Hons, 1991) from the University of Glasgow, in the top few in the year. Work as a junior doctor witnessing fatal cardiovascular disease inspired a career in cardiovascular pathology. He then moved to the University of Cambridge and did a PhD on mechanisms of macrophage-induced vascular smooth muscle cell apoptosis with Professors Peter Weissberg and Martin Bennett and Dr David Bowyer.
He is fully clinically trained in histopathology, mainly at Cambridge, and specialised in cardiovascular, renal and pulmonary pathology. He then moved to Hammersmith Hospital, Imperial College London for six years as a full-time consultant pathologist with an interest in renal / cardiovascular pathology.
Dr Boyle’s research focus is in connecting the functional genomics of macrophage differentiation with clinical cardiovascular and renal pathology with a view to improved pharmacology.
Dr Boyle became a BHF Intermediate Clinical Research Fellow with Professor Dorian Haskard working on novel macrophage inactivation pathways, initially discovered in intraplaque haemorrhage in the coronary arteries of patients with fatal acute coronary syndrome. These evoke macrophages with decreased inflammatory activation, a phenotype we termed Mhem.
This work identified a new transcriptional pathway driven by ATF1, allowing coordination between iron recycling, cholesterol recycling and anti-inflammatory effects in macrophages after haemorrhage. This has exciting implications for treatment, especially since we have now found that it can also be stimulated by the diabetic agent metformin via AMP-Kinase.
Dr Boyle then honed his diagnostic skills at Papworth Hospital Cambridge before coming back to Imperial as a BHF Senior Clinical Research Fellow to develop mechanistic and translational studies of the AMPK-ATF1-Mhem pathway. Dr Boyle now heads the growing Macrophage Differentiation research group.
Recent achievements have included:
Showed the mechanism by which heme normally induces Heme Oxygenase 1, the catabolic enzyme that safely clears its iron into storage. This is via Activating Transcription Factor 1 (ATF1) and also Nuclear Factor of Erythroid Cells Like 2 (NFE2L2, Nrf2).
Showed that ATF1 coregulates iron and lipid handling.
Showed that metformin may suppresse atherosclerosis in vivo via macrophage AMPK, rather than via an effect on blood glucose.
Showed that normal resolution of tissue hemorrhage in vivo requires AMPK and ATF1; and their deficiency results in inflammation and oxidative stress.
Showing a novel epigenetic mechanism of specificity of stimulus-dependent gene induction.
British Atherosclerosis Society John French Lecture
University of Glasgow Tenovus Lecture
Multiple national and international invited seminars.
et al., 2013, 5 '-AMP-Activated Protein Kinase-Activating Transcription Factor 1 Cascade Modulates Human Monocyte-Derived Macrophages to Atheroprotective Functions in Response to Heme or Metformin, Arteriosclerosis Thrombosis and Vascular Biology, Vol:33, ISSN:1079-5642, Pages:2470-2480
et al., 2011, Activating Transcription Factor 1 Directs Mhem Atheroprotective Macrophages Through Coordinated Iron Handling and Foam Cell Protection., Circulation Research
et al., 2011, Heme Induces Heme Oxygenase 1 via Nrf2 Role in the Homeostatic Macrophage Response to Intraplaque Hemorrhage, Arteriosclerosis Thrombosis and Vascular Biology, Vol:31, ISSN:1079-5642, Pages:2685-U826
et al., 2009, Coronary Intraplaque Hemorrhage Evokes a Novel Atheroprotective Macrophage Phenotype, American Journal of Pathology, Vol:174, ISSN:0002-9440, Pages:1097-1108