J. Geoffrey Pickering

J. Geoffrey Pickering, Professor, Departments of Medicine, Biochemistry, and Medical Biophysics

Why I Became a Scientist

I trained as both a cardiologist and a scientist.  I became a clinician-scientist because of my interest and recognition that the problems faced by individuals with heart disease must be addressed not only by existing treatment strategies but by gaining a better understanding of the cell and molecular basis for the disease.

Research Summary

Our work involves the identification of pathways by which cells of the artery wall contribute to vascular disease.  This includes studying the diverse behaviour patterns of the vascular smooth muscle cell.  Our laboratory has international prominence in the field of smooth muscle cell motility and interactions with the extracellular matrix as well as vascular stabilization.

We are currently one of the few groups capable of cloning smooth muscle cells from human arteries and we generated the first, and to date only, smooth muscle cell lines that have the capacity to reversibly convert between a contracting (healthy) and noncontracting (diseased or repairing) state. This has led to the discovery of novel genes involved in vascular remodeling.  Determining the role of these genes in vascular disease is a major direction of the lab.

Another focus is to understand, at a molecular level, how the vascular system ages.  Accelerated aging of blood vessels leads to heart disease and stroke.  We also investigate novel strategies for the development of new blood vessels (angiogenesis).

Research Questions

Can we extend the productive lifespan of vascular cells?

The ability of vascular cells to retain their functions as we age is essential for cardiovascular health.   Avoiding high blood pressure, heart attacks, strokes, and improving recovery following stenting and bypass surgery, requires that vascular cells do not age faster than the rest of the body.  We have discovered novel pathways that slow vascular cell aging.

How do vascular cells communicate with extracellular matrix?  

Heart attacks and strokes develop when the structure of atherosclerotic plaques break down.  Understanding how to develop a stable, collagen-rich extracellular matrix is critical to stabilizing vulnerable plaques and preventing the dire consequences of their rupture.  We are studying novel pathways that improve and stabilize the interactions between cells and collagen.

How can endothelial cells and vascular smooth muscle cells interact to regenerate new blood vessels in diseased hearts?

When hearts become starved of oxygen they attempt to generate new blood vessels.  However this process is often not successful because the new blood vessels are thin-walled and unstable.  By regenerating durable blood vessels that have all cell layers, new strategies for managing heart disease can be developed.

Education
  • M.D., Faculty of Medicine, Queen's University, Kingston, Ontario
  • Ph.D., Department of Medical Biophysics, University of Western Ontario, London, Ontario
  • Specialty Certification (FRCP(C)) in Internal Medicine and Cardiology
Training
  • Internal Medicine Residency, University of Toronto
  • Internal Medicine Certification and Fellowship, Royal College of Physicians and Surgeons of Canada
  • Cardiology Residency, University of Western Ontario
  • Cardiology Certification by Royal College of Physicians and Surgeons of Canada
  • Cardiology Research Fellow, University of Western Ontario
  • Post-Doctoral Training, Tufts University School of Medicine, Boston, MA
Awards
  • Heart and Stroke Foundation of Ontario / Barnett-Ivey Chair 
  • Queen's Honour Matriculation Award
  • Ivan Smith Scholarship
  • W.W. Near and Susan Near Special Scholarship
  • Rueben Wells Leonard Penultimate Year Scholarship, Queen's University
  • Research Fellowship, Canadian Heart Foundation
  • Detweiler Travel Fellowship, Royal College of Physicians and Surgeons of Canada
  • Research Fellowship, Medical Research Council of Canada
  • Young Investigator Award, Canadian Cardiovascular Society
  • Research Scholarship, Medical Research Council of Canada
  • Premier's Research Excellence Award
  • Operating Grants: Heart and Stroke Foundation & Canadian Institutes of Heath Research
  • University Students' Council Teaching Honour Roll Award of Excellence
  • Department of Medicine Research Award of Excellence
  • University of Western Ontario, Faculty of Medicine and Dentistry, Dean’s Award of Excellence in Research
  • Career Investigator Award, Heart and Stroke Foundation of Ontario 
  • Fellow, American Heart Association
  • Fellow, American College of Cardiology
  • Senior Investigator Award, Hypertension Canada
  • Tony Graham Award for Excellence in Board Service, Heart and Stroke Foundation
  • Luis G. Melo Memorial Lecturer in Molecular Cardiology, Queen's University
  • WORLDiscoveries Vanguard Award
  • Western Alumni of Distinction Award - Excellence in Basic Science Research
  • Ken Bowman Research Achievement Award, Institute of Cardiovascular Sciences, University of Manitoba
  • Fellow of the Canadian Academy of Health Sciences (CAHS), Induction Ceremony in Vancouver, BC
Publications
  • Watson A*, Nong Z, Yin H*, O’Neil C, Fox S, Balint B*, Guo L, Leo O, Chu MWA, Gros R, Pickering JG. Nicotinamide phosphoribosyltransferase in smooth muscle cells maintains genome integrity, resists aortic medial degeneration and is suppressed in human thoracic aortic aneurysm disease.  Circulation Research. 120:1889-1902, 2017. (Featured on the cover, in an Editorial, and as an Issue Highlight).   
  • Arpino JM*, Nong Z, Li F, Yin H*, Ghonaim N, Milkovich S, Balint B*, O’Neil C, Fraser GM, Goldman D, Ellis CG, Pickering JG.  Four-dimensional microvascular analysis reveals that regenerative angiogenesis in ischemic muscle produces a flawed microcirculation.   Circulation Research 120:1453-1465, 2017.  (Featured as Editor’s pick and in an Editorial).
  • Xu Y*, Pickering JG, Nong Z, Ward AD. Segmentation of digitized histological sections for quantification of the muscularized vasculature in the mouse hind limb.  Journal of Microscopy 266:89-103, 2017.
  • Elkerton JS, Xu Y, Pickering JG, Ward A.  Differentiation of arterioles from venules in mouse histology images using machine learning.  Journal of Medical Imaging 4:021104, 2017.  
  • Feldman RD., Harris SB., Hegele RA., Padwal R., Pickering JG., Rockwood K.  Applying atherosclerotic risk prevention guidelines to the elderly: A bridge too far.  Canadian Journal of Cardiology.  32:598-602, 2016. 
  • Yin H., Pickering JG.  Cellular senescence and vascular disease: Novel routes to better understanding and therapy.  Canadian Journal of Cardiology.  32:612-623, 2016.
  • Gros R, Hussain Y, Chorazyczewski J, Pickering JG, Ding Q and Feldman RD. The extent of vascular remodeling is dependent on the balance between ERα and GPER. Hypertension.  68:1225-1235, 2016.  
  • Pang DK, Nong Z*, Sutherland BG, Sawyez SG, Robson DL, Toma J, Pickering JG, Borradaile NM.  Niacin promotes revascularization and recovery of limb function in diet induced obese mice with peripheral ischemia.  Pharmacology Research and Perspectives 4(3) e0233, 2016. 
  • Said S*, Yin H*, Pickering JG, Mequinint K. Concurrent and sustained delivery of FGF2 and FGF9 from electrospun poly(ester amide) fibrous mats for therapeutic angiogenesis.  Tissue Engineering.  22(7-8):584-96, 2016. 
  • Feldman RD, Ding Q, Hussain Y, Limbird LE, Pickering JG, Gros R. Aldosterone mediates metastatic spread of renal cancer via the G protein-1 coupled receptor, GPER.  FASEB Journal. 30:2086-2096, 2016. 
  • Yin H*, Frontini MJ*, Arpino JM*, Nong Z, O’Neil C, Xu Y*, Balint B, Ward AD, Chakrabarti S, Ellis CG, Gros R, Pickering JG.  Fibroblast Growth Factor 9 imparts hierarchy and vasoreactivity to the microcirculation of renal tumors and suppresses metastases.  Journal of Biological Chemistry 290:22127-22142, 2015.
  • Xu Y*, Pickering JG, Nong Z, Gibson E, Arpino JM*, Yin H*, Ward AD.  A method for 3D histopathology reconstruction supporting mouse microvasculature analysis.  PLoS One.  10:e0126817, 2015.
  • Balint B*, Yin H*, Chakrabarti S, Chu MWA, Sims SM, Pickering JG.  Collectivization of vascular smooth muscle cells via TGF-ß–cadherin-11-dependent adhesive switching. Arteriosclerosis, Thrombosis and Vascular Biology 35:1254-1264, 2015. 
  • Xu Y*, Pickering JG, Nong Z, Ward AD.  Segmentation of digitized histological sections for vasculature quantification in the mouse hind limb SPIE Medical Imaging 2015: Digital Pathology 9420, 2015. 
  • Huff MW, Pickering JG.  Can a vascular smooth muscle-derived foam-cell really change its spots?   Arteriosclerosis, Thrombosis, and Vascular Biology 35:492-495, 2015. 
  • Said S*, Pickering JG, Mequinint K. Controlled delivery of Fibroblast Growth Factor-9 from biodegradable poly(ester amide) fibers for building functional neovasculature.  Pharmaceutical Research 31:3335-3347, 2014.  
  • Sandiford S, Kennedy K, Xie X, Pickering JG, and Li S.  Dual oxidase maturation factor 1 (DUOXA1) overexpression increases reactive oxygen species production and inhibits murine muscle satellite cell differentiation.  Cell Communication and Signaling 12:5 (1-15) 2014.
  • Dunmore-Buyze J, Tate  E, Xiang F, Detombe SA, Nong Z, Pickering JG, Drangova M. Three-dimensional imaging of the mouse heart and vasculature using micro-CT and whole-body perfusion of iodine or phosphotungstic acid.  Contrast Media and Molecular Imaging 9:383-390, 2014.
  • Bojic LA, Burke AC, Chhoker S, Telford DE, Sutherland BG, Edwards JY, Sawyez CG, Tirona RG, Yin H*, Pickering JG, and Huff MW.  PPARδ agonist GW1516 attenuates diet-induced aortic inflammation, insulin resistance and atherosclerosis in Ldlr-/- mice. Arteriosclerosis, Thrombosis and Vascular Biology 34:52-60, 2014.  (Featured in an Editorial and on the cover.)  
  • Vafaie F*, Yin H*, O’Neil C, Nong Z, Watson A*, Arpino JM*, Chu MWA, Holdsworth D, Gros R, Pickering JG.  Collagenase-resistant collagen promotes mouse aging and vascular cell senescence.  Aging Cell 13:121-30, 2014.  
  • Xu Y*, Pickering JG, Nong Z, Gibson E, Ward AD.  3D reconstruction of digitized histological sections for vasculature quantification in the mouse hind limb.  SPIE Proceedings 9041, Medical Imaging 2014: Digital Pathology, 9041, 2014. 
  • van der Veer E*, Kraaijeveld AO, de Bruin RG, de Vries MR, Verschuren JW, Pons D, Segers FM, Beckers CM,  van Santbrink PJ, Trompet S, Janssen A, Bot I, Peters EA, de Boer H, van der Wal AC, Richard S, Tio RA, de Winter RJ, Doevendans PA, Zwinderman AH, Slagboom PE,  Pickering JG, Rabelink TJ, Goumans MJ, van Berkel TJC, Quax PHA, Jukema JW, Biessen, EAL, van Zonneveld AJ.  Quaking, an RNA-binding protein, is a critical regulator of vascular smooth muscle cell phenotype.  Circulation Research 13:1065-1075, 2013.
  • Yin H*, van der Veer E*, Frontini MJ*, Thibert V*, O’Neil C, Watson A*, Szasz P*, Chu MWA, Pickering JG.  Intrinsic directionality of migrating vascular smooth muscle cells is regulated by NAD+ biosynthesis.  Journal of Cell Science 125:5770-5780, 2012.
  • Beyea MC, Esmonde S, Sawyez CG, Edwards JY, Hegele RA, Pickering JG, Huff MW.  The oxysterol, 24(S),25-epoxycholesterol attenuates human smooth muscle-derived foam cell formation via reduced LDL uptake and enhanced LXR-mediated cholesterol efflux. Journal of the American Heart Association, 1:e810, pp 1-15, 2012.  http://jaha.ahajournals.org/content/1/3/e000810
  • Frontini MJ, Nong Z, Gros R, Drangova M, O'Neil C, Rahman MN, Akawi O, Yin H, Ellis CG, Pickering JG.  Fibroblast growth factor 9 delivery during angiogenesis produces durable, vasoresponsive microvessels wrapped by smooth muscle cells. Nature Biotechnology (Featured in Editorial and on Cover). 29: 421-427, 2011.
  • Nong Z, O'Neil C, Lei M, Gros R, Watson A, Rizkalla A, Mequanint K, Li S, Frontini MJ, Feng Q, Pickering JG. Type I collagen cleavage is essential for effective fibrotic repair after myocardial infarction. American Journal of Pathology. 179: 2189-2198, 2011.
  • Borradaile NM, Pickering JG. Nicotinamide phosphoribosyltransferase imparts human endothelial cells with extended replicative lifespan and enhanced angiogenic capacity in a high glucose environment. Aging Cell. 8: 100-112, 2009.
  • Frontini MJ, O'Neil C, Sawyez C, Chan BM, Huff MW, Pickering JG. Lipid incorporation inhibits Src-dependent assembly of fibronectin and type I collagen by vascular smooth muscle cells. Circulation Research. 104: 832-841, 2009.
  • Small TW, Pickering JG. Nuclear degradation of Wilms tumor 1-associating protein and surviving splice variant switching underlie IGF-1-mediated survival. The Journal of Biological Chemistry. 284: 24684-24695, 2009.
  • Ho C, van der Veer E, Akawi O, Pickering JG. SIRT1 markedly extends replicative lifespan if the NAD+ salvage pathway is enhanced. FEBS Letters. 583: 3081-3085, 2009.
  • van der Veer E, Ho C, O'Neil C, Barbosa N, Scott R, Cregan SP, Pickering JG. Extension of human cell lifespan by nicotinamide phosphoribosyltransferase. Journal of Biological Chemistry (Accelerated Publication, top 5% of submissions). 282: 10841-10845, 2007.
  • Small TW, Bolender Z, Bueno C, O’Neil C, Rushlow W, Rajakumar N, Kandel C, Strong J, Madrenas J, Pickering JG.  Wilms’ tumor 1-associating protein regulates the proliferation of vascular smooth muscle cells. Circulation Research. 99: 1338-1346, 2006.
  • van der Veer E, Nong Z, O’Neil C, Urquhart B, Freeman D, Pickering JG.  Pre-B-Cell colony enhancing factor regulates NAD+-dependent protein deacetylase activity and maturation of human vascular smooth muscle cells. Circulation Research (Featured in Editorial). 97: 16-24, 2005.
  • Van Den Diepstraten C, Papay K, Bolender Z, Brown A, Pickering JG.  Cloning of a novel prolyl 4-hydroxylase subunit expressed in the fibrous cap of human atherosclerotic plaque. Circulation. 108: 508-511, 2003.
  • Li S, Van Den Diepstraten C, D’Souza SJ, Chan BMC, Pickering JG.  Vascular smooth muscle cells orchestrate the assembly of type I collagen via alpha2ß1 integrin, RhoA and fibronectin polymerization. American Journal of Pathology (Featured on Cover). 163: 1045-1056, 2003.
  • Li S, Fan Y-S, Chow LH, Van Den Diepstraten C, van der Veer E, Sims S, Pickering JG. Innate diversity of adult human arterial smooth muscle cells: cloning of distinct subtypes from the internal thoracic artery. Circulation Research. 89: 517-525, 2001.
  • Rocnik E, Chow LH, Pickering JG.  Heat shock protein 47 is expressed in fibrous regions of human atheroma and is regulated by growth factors and oxidized low density lipoprotein. Circulation (Featured in Editorial). 101: 1229-1233, 2000.
  • Wang H, DeVries ME, Deng S, Khandaker ME, Pickering JG, Chow LH, Garcia B, Kelvin DJ, Zhong B. The axis of interleukin 12 and gamma interferon regulates acute vascular xenogenetic rejection. Nature Medicine. 6: 549-555, 2000.
  • Pickering JG, Chow LH, Li S, Rogers KA, Rocnik E, Zhong R, Chan BMC.  Alpha5ß1 integrin expression and luminal edge fibronectin matrix assembly by smooth muscle cells following arterial injury. American Journal of Pathology (Featured on Cover). 156: 453-465, 2000.
  • Li S, Chow LH, Pickering JG.  Cell surface bound collagenase 1 and focal substrate degradation stimulate the rear release of motile vascular smooth muscle cells. Journal of Biological Chemistry. 275: 35384-35392, 2000.
  • Li S, Sims S, Jiao Y, Chow LH, Pickering JG.  Evidence from a novel human cell clone that adult vascular smooth muscle cells can convert reversibly between noncontractile and contractile phenotypes. Circulation Research. 85: 338-348, 1999.
  • Rocnik E, Chan BMC, Pickering JG.  Evidence for a role of collagen synthesis in arterial smooth muscle cell migration. Journal of Clinical Investigation. 101: 1889-1898, 1998.
  • Pickering JG, Ford CM, Tang B, Chow LH.  Coordinated effects of basic fibroblast growth factor 2 on expression of fibrillar collagens, matrix metalloproteinases, and tissue inhibitors of matrix metalloproteinases by human vascular smooth muscle cells. Evidence for repressed collagen.  Arteriosclerosis, Thrombosis, and Vascular Biology. 17: 475-482, 1997.
  • Pickering JG, Uniyal S, Ford CM, Chau T, Laurin MA, Chow LH, Ellis CG, Fish J, Chan BMC.  Fibroblast growth factor 2 potentiates vascular smooth muscle cell migration to platelet derived growth factor: Upregulation of alpha2ß1 integrin and disassembly of actin filaments. Circulation Research. 80: 627-637, 1997.
  • Pickering JG, Weir L, Jekanowski J, Kearney M, Isner JM.  Proliferative activity in peripheral and coronary atherosclerotic plaque among patients undergoing percutaneous revascularization. Journal of Clinical Investigation. 91: 1469-1480, 1993.
  • Pickering JG, Weir L, Rosenfield K, Stetz J, Jekanowski J, Isner JM.  Smooth muscle cell out growth from human atherosclerotic plaques: Implications for the assessment of lesion biology. Journal of the American College of Cardiology. 20: 1430-1439, 1992.

 

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Contact Info

Ilda Moniz
imoniz@robarts.ca
Administrative Assistant, Research
519-931-5718

Kathy Serafin
Kathy.serafin@lhsc.on.ca
Administrative Assistant, Clinical
519-663-5777 x33973