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
Publications
  • 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  
  • 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.  
  • 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.  
  • 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. 
  • 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.  
  • 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.)  
  • 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.  
  • 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.
  •  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.  
  • 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.  
  • 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. 
  • 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, Gibson E, Arpino JM*, Yin H*, Ward AD.  A method for 3D histopathology reconstruction supporting mouse microvasculature analysis.  PLoS One.  10:e0126817, 2015.
  •  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.
  •  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. 
  • 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. 
  • 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. 
  • 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.  
  • Yin H., Pickering JG.  Cellular senescence and vascular disease: Novel routes to better understanding and therapy.  Canadian Journal of Cardiology.  32:612-623, 2016.
  •  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. 
  • 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.   
  • 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.
  • 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).  
  • 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).  
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