Ormiston, Mark - Queen's University - Department of Biomedical and Molecular Sciences

个人简介

Tier 2 Canada Research Chair in Regenerative Cardiovascular Medicine Postdoctoral Fellowship: University of Cambridge Department of Medicine, Respiratory Division, Cambridge, UK PhD: Biomedical Engineering and Cardiovascular Sciences, University of Toronto and St. Michael’s Hospital, Toronto, Canada MASc: Chemical and Biomedical Engineering, University of Toronto Faculty of Applied Science & Engineering, Toronto, Canada BScE: Chemical Engineering, Queen’s University Faculty of Engineering and Applied Science, Kingston, Canada

研究领域

My research is centered on the cellular mechanisms governing vascular remodeling in health and disease, with a particular focus on the capacity of circulating cells of the immune system to regulate blood vessel integrity, growth and repair. This interest is rooted in my study of pulmonary arterial hypertension (PAH), a disease of pathological vascular remodeling and right heart failure that is linked to immune dysfunction. PAH is strongly associated with loss-of-function mutations in the bone morphogenetic protein (BMP) type II receptor (BMPR-II), a receptor of the transforming growth factor-β (TGFβ) superfamily. Identification of this link between PAH and BMPR-II haploinsufficiency has provided considerable insight into the mechanisms governing pulmonary vascular homeostasis and makes PAH an ideal candidate for proof-of-concept regenerative and cell-based therapeutic strategies. More specifically, I am interested in the capacity of innate lymphocytes, such as Natural Killer (NK) cells, to influence vascular growth and repair. Beyond their traditional role as the cytotoxic effector cells of innate immunity, there is a growing body of literature supporting a role for NK cells in the regulation of vascular remodelling, particularly in pregnancy. My previous work has identified a phenotypic and functional defect in the circulating NK cells of PAH patients, associated with increased TGFβ signalling and elevated production of matrix metalloproteinase (MMP)-9 by these cells. Through my ongoing studies, I aim to (i) determine the mechanisms by which NK cells influence pulmonary vascular homeostasis in health and disease and (ii) clarify the impact of BMPR-II mutations on these processes.

近期论文

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Hong Z, Chen KH, Dasgupta A, Potus F, Dunham-Snary K, Bonnet S, Tian L, Fu J, Breuils-Bonnet S, Provencher S, Wu D, Mewburn J, Ormiston ML, Archer SL. miR-138 and miR-25 downregulate MCU, causing pulmonary arterial hypertension's cancer phenotype. Am J Respir Crit Care Med. 2016 Sep 20. [Epub ahead of print] PMID: 27648837 Long L, Ormiston ML (joint first author), Yang X, Southwood M, Gräf S, Machado RD, Mueller M, Kinzel B, Yung LM, Wilkinson JM, Moore SD, Drake KM, Aldred MA, Yu PB, Upton PD, Morrell NW. Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension. Nat Med. 2015 Jun 15. PMID: 26076038 Ormiston ML, Deng Y, Rundle N, Bendjelloul F, Tsoporis JN, Parker TG, Stewart DJ, Courtman DW. A lymphocyte-dependent mode of action for imatinib mesylate in experimental pulmonary hypertension. Am J Pathol. 2013 May;182(5):1541-51. PMID: 23518411 Geti I, Ormiston ML (joint first author), Rouhani F, Toshner M, Movassagh M, Nichols J, Mansfield W, Southwood M, Bradley A, Rana AA, Vallier L, Morrell NW. A practical and efficient cellular substrate for the generation of induced pluripotent stem cells from adults: blood-derived endothelial progenitor cells. Stem Cells Transl Med. 2012 Dec;1(12):855-65. PMID: 23283547 Ormiston ML, Chang C, Long LL, Soon E, Jones D, Machado R, Treacy C, Toshner MR, Campbell K, Riding A, Southwood M, Pepke-Zaba J, Exley A, Trembath RC, Colucci F, Wills M, Trowsdale J, Morrell NW. Impaired natural killer cell phenotype and function in idiopathic and heritable pulmonary arterial hypertension. Circulation. 2012 Aug 28;126(9):1099-109. PMID: 22832786 Ormiston ML, Deng Y, Stewart DJ, Courtman DW. Innate immunity in the therapeutic actions of endothelial progenitor cells in pulmonary hypertension. Am J Respir Cell Mol Biol. 2010 Nov;43(5):546-54. PMID: 19995942 For a complete list of publications, click here. Book Chapters M.L. Ormiston and N.W. Morrell. “Chapter 7: Pathobiology of pulmonary hypertension” in Pulmonary Circulation: Diseases and their Treatment, 4th Edition. Edited by A Peacock, R. Naeije and L.J. Rubin. Taylor and Francis Group Ltd, Oxford, UK. In press. M.L. Ormiston and N.W. Morrell. Chapter Title: “Targeting BMPR-II deficiency for the treatment of pulmonary arterial hypertension” in Recent Advances in Cardiology, Volume 17. Edited by Derek Rowlands and Bernard Clarke. JP Medical Ltd, London, UK. In press. M.L. Ormiston, D.W. Courtman, D.J. Stewart. “Chapter 16.7: Stem Cell Therapy” in Pulmonary Circulation, 3rd Edition. Edited by A Peacock, R. Naeije and L.J. Rubin. Hodder Arnold, London, UK. Published May 27, 2011.