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 qualified in Pharmacology (Class I Hons, 1988, plus Prize) 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 its pathogenesis. He moved to the University of Cambridge and did a PhD with Professors Peter Weissberg and Martin Bennett and Dr David Bowyer.
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 and defined its driving transcription factor, which is Activating Transcription Factor 1 (ATF1).
Dr Boyle then became a BHF Senior Clinical Research Fellow to develop mechanistic and translational studies of the AMPK-ATF1-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.
- chromatin remodelling contributes to the specificity of gene activation that distinguishes leukocyte resolution from erythrocyte resolution whilst they use related transcription factor binding sites.
He has overall carried out a track of work showing first that plaque inflammation is associated with plaque rupture (shortly after graduation). Then, that plaque macrophages kill vascular smooth muscle cells largely via apoptosis and Fas-Ligand (PhD). Then, he worked to describe a plaque macrophage population that reacts to intraplaque hemorrhage and suppresses its pro-atherogenic effects (so the plaque is better off with them than without them). Then, he showed the transcriptional mechanism driving these macrophages is mediated by AMPK and ATF1. Then he showed that this pathway operates in vivo and may be used therapeutically to decrease atherosclerosis.
Further work will compare the responses of macrophages in erythrocyte resolution with leukocyte resolution. This is yielding very novel insights into gene regulation and translational pathways to reduce cardiovascular disease.
He is fully clinically trained in histopathology, mainly at Cambridge, and specialised in cardiovascular and renal pathology. He then moved to Hammersmith Hospital, Imperial College London for six years as a full-time pathologist with an interest in renal / cardiovascular pathology. he continues to hold Specialist registration in Histopathology. This background, as well as the pharmacological possibilities, informs his research.
British Atherosclerosis Society John French Lecture
University of Glasgow Tenovus Lecture
Multiple national and international invited seminars.
et al., 2020, Hematoma resolution in vivo is directed by Activating Transcription Factor 1 (ATF1), Circulation Research, Vol:127, ISSN:0009-7330, Pages:928-944
et al., 2020, Metformin directly suppresses atherosclerosis in normoglycemic mice via haematopoietic Adenosine Monophosphate-Activated Protein Kinase (AMPK), Cardiovascular Research, ISSN:0008-6363
et al., 2019, Cartilage oligomeric matrix protein associates with a vulnerable plaque phenotype in human atherosclerotic plaques, Stroke, Vol:50, ISSN:0039-2499
et al., 2019, The transcription factor ERG regulates super-enhancers associated with an endothelial-specific gene expression program, Circulation Research, Vol:124, ISSN:0009-7330, Pages:1337-1349
et al., 2015, Developmental origin of age-related coronary artery disease, Cardiovascular Research, Vol:107, ISSN:0008-6363, Pages:287-294
et al., 2014, Requirement of JNK1 for endothelial cell injury in atherogenesis, Atherosclerosis, Vol:235, ISSN:1879-1484, Pages:613-618
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
Boyle JJ, 2012, Heme and haemoglobin direct macrophage Mhem phenotype and counter foam cell formation in areas of intraplaque haemorrhage., Curr Opin Lipidol, Vol:23, Pages:453-461
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
et al., 2019, SMARCA4 REDIRECTS BINDING OF MACROPHAGE ACTIVATING TRANSCRIPTION FACTOR 1 (ATF1) FROM GENES FOR INFLAMMATION RESOLUTION TO GENES FOR ERYTHROCYTE RESOLUTION, 87th Congress of the European-Atherosclerosis-Society (EAS), ELSEVIER IRELAND LTD, Pages:E78-E78, ISSN:0021-9150