Research and teaching
- Atherosclerosis, Inflammation, Cholesterol
- Heat shock protein 27
- Auto-antibodies, Immunology, Vaccination,
- Estrogens , Estrogen receptors, Women's health, Menopause
Dr. Ed O’Brien is a Cardiologist and Director of the Vascular Biology Research laboratory that studies how the body develops the right responses to combat the development of hardening of the arteries (or “atherosclerosis”). We are interested in developing therapies to reduce cholesterol levels and unbridled inflammation. A decade ago, we discovered Heat Shock Protein 27 (HSP27) as a protein that is in part regulated by estrogens and is associated with cardiovascular health. Importantly, levels of HSP27 drop with menopause – hence, we have developed HSP27 "replacement therapy" using a novel vaccination approach. HSP27 can up-regulate the expression of liver receptors that clear cholesterol from the circulation - an important breakthrough that could revolutionize the treatment of cholesterol disorders. HSP27 immuno-therapies may be useful for combating not only heart disease in post-menopausal women, but other chronic degenerative and inflammatory disorders in men and women (e.g., dementia, inflammatory liver disease). Dr. O’Brien is a member of the Women’s Heart and Brain Health Research Steering Committee for the Heart and Stroke Foundation of Canada and a senior co-author of Cardiology section of “The Science of Sex & Gender in Human Health”, an on-line course developed by the Office of Research on Women’s Health at the US National Institutes of Health in conjunction with the Office of Women’s Health at the US Food and Drug Administration.
- M.H. Chiu, C. Shi, M. Rosin, Z. Batulan, E.R. O’Brien. Biophysical analyses and functional implications of the interaction between Heat Shock Protein 27 and antibodies to HSP27 (under revision)
- V. Raparelli, B. Hibbert, E.R. O’Brien. Lowering Women's Cholesterol Levels with Therapies Beyond Statins: A Sex-disaggregated Meta-Analysis of PCSK9 monoclonal antibody therapies (under revision)
- C. Shi, A. Ulke-Lemee, J. Deng , Z. Batulan, E.R. O’Brien. Characterization of Heat Shock Protein 27 in Extracellular Vesicles: A Potential Anti-inflammatory Therapy. FASEB J 2019 Feb. 1, 2019; 33(2): 1617-1630. doi: 10.1096/fj.201800987R
- M.H. Chiu, B. Heydari, Z. Batulan, V. Subramanya, K. Schenck-Gustafsson, E.R. O’Brien. Coronary Artery Disease in Post-Menopausal Women: Are There Appropriate Means of Assessment? Clinical Science (2018) 132 1937–1952. https://doi.org/10.1042/CS20180067
- Z. Batulan, Y. Li, G.A. Koumbadinga, V.K. Pulakazhi Venu, E.R. O’Brien. Extracellular Release and Signaling by Heat Shock Protein 27: Role in Modifying Vascular Inflammation. Frontiers in Immunology. 2016 Jul 26;7:285. doi: 10.3389/fimmu.2016.00285.
- X. Ma, B. Hibbert, M. McNulty, T. Hu, X. Zhao, F. D. Ramirez, T. Simard, J. de Belleroche, E.R. O’Brien. Heat Shock Protein 27 Attenuates Neointima Formation and Accelerates Re-endothelialization after Arterial Injury and Stent Implantation: Importance of Vascular Endothelial Growth Factor Up-regulation. FASEB J. 2014 Feb 18; 28(2):594-602
- J.E. Raizman, Y.X. Chen, T. Seibert, B. Hibbert, C.M. Cuerrier, S. Salari, X. Zhao, T. Hu, C. Shi, X. Ma, T. Simard, J. Caravaggio, K. Rayner, D. Bowdish, K. Moore, E.R. O'Brien. Heat Shock Protein-27 Attenuates Foam Cell Formation and Atherogenesis by Down-regulating Scavenger Receptor-A Expression via NF-κB Signaling. BBA - Molecular and Cell Biology of Lipids. 2013 Dec;1831(12):1721-8.
- T. Seibert, B. Hibbert, Y.-X. Chen, T. Simard, T. Hu, C.M. Cuerrier, X. Zhao, K. Rayner, D.J. Wells, J. de Belleroche, B. Chow, K.R Wilson, S. Hawken, E.R. O’Brien. Serum heat shock protein 27 levels represent a potential therapeutic target for atherosclerosis. Journal of the American College of Cardiology Journal of the American College of Cardiology. 2013;62(16):1446-1454.
- C. Cuerrier, Y.-X. Chen, D. Tremblay, K. Rayner, M. McNulty, X. Zhao, C. Kennedy, J. de BelleRoche, A. Pelling, E.R. O’Brien. Chronic Over-expression of Heat Shock Protein 27 Results in Favorable Plaque Remodeling: Attenuated Cholesterol and Macrophage Accumulation with Enhanced Collagen Content. PLOS-One 2013. 8(2): e55867.
- S. Salari, T. Seibert, Y.-X. Chen, T. Hu, C. Shi, X. Zhao, C.M. Cuerrier, J.E. Raizman, E.R. O’Brien. Extracellular HSP27 Acts as a Signaling Molecule to Activate NF-kB in Macrophages. Cell Stress & Chaperones 2013; 18(1):53-63. DOI: 10.1007/s12192-012-0356-0; PMID:22851137.
- J. Sun, X. Ma, Y-X. Chen, K. Rayner, B. Hibbert, M. McNulty, B. Dhaliwal, D. Ramirez, E.R. O’Brien. Attenuation of Atherogenesis via the Anti-Inflammatory Effects of Selective Activation of Estrogen Receptor Beta 8β-VE2 J Cardiovasc Pharmacol. 2011; 58(4):399-405.
- K. Rayner, J. Sun,Y-X Chen, M. McNulty, T. Simard, X. Zhao, DJ. Wells, J. de Belleroche, E.R. O’Brien. Heat Shock Protein 27 Protects Against Atherogenesis via an Estrogen-Dependent Mechanism: Role of Selective Estrogen Receptor Beta Modulation. Arteriosclerosis, Thrombosis, and Vascular Biology 2009; 29:1751-56.
- K. Rayner, Y.-X. Chen, M. McNulty, T. Simard, X. Zhao, J. de Belleroche, D.J. Wells, E.R. O’Brien Extracellular Release of the Atheroprotective Heat Shock Protein 27 Is Mediated by Estrogen and Competitively Inhibits acLDL Binding to Scavenger Receptor-A. Circ Research 2008;103:133-141.
- A.S. Al-Madhoun, Y.-X. Chen, L. Haidari, K. Rayner, W. Gerthoffer, H. McBride, E.R. O'Brien The Interaction and Cellular Localization of HSP27 and Estrogen Receptor-β are Modulated by 17β-Estradiol and HSP27 Phosphorylation. Molecular & Cellular Endocrinology 2007; 270:33-42.
- H. Miller, S. Poon, B. Hibbert, K. Rayner, Y.-X. Chen, E.R. O’Brien. Modulation of Estrogen Signalling by the Novel Interaction of HSP27, a Biomarker of Atherosclerosis, and Estrogen Receptor Beta: Mechanistic Insights in the Vascular Effects of Estrogens Arterioscler Thromb Vasc Biol 2005;25:e10-e14.