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.
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 and Disease Implications
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.
• 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
• 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
• 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
• 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.
• Gros R, Ding Q, Armstrong S, O’Neil C, Pickering JG, Feldman RD. Rapid effects of aldosterone on clonal human vascular smooth muscle cells. American Journal of Physiology (Cell) 292: C788-C94, 2007.
• 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 282:10841-10845, 2007 (Accelerated Publication).
• Gros R, Van Uum, S, Ding QM, Pickering JG, Hegele RA, Feldman RD. Increased enzyme activity and increased beta-adrenergic-mediated vasodilation in subjects expressing a single nucleotide variant of human adenylyl cyclase 6. Arteriosclerosis Thrombosis and Vascular Biology 27:2657-2663, 2007.
• Ho H, Hou G, Pickering JG, Hannigan G, Langille BL, Bendeck MP. Integrin linked kinase in the vascular smooth muscle cell response to injury. American Journal of Pathology 173:278-88, 2008.
• Borradaile N and 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 M, O'Neil C, Sawyez C, Chan BMC, Huff M, Pickering JG. Lipid Incorporation Inhibits Src-Dependent Assembly of Fibronectin and Type I Collagen by Vascular Smooth Muscle Cells. Circulation Research 104:832-41 2009. (Accompanied by Editorial)
• Choi HY, Rahmani M, Wong BW, Allahverdian S, McManus BM, Pickering JG, Chan T, Francis GA. ATP-binding cassette transporter A1 expression and apolipoprotein A-I binding are impaired in intima-type arterial smooth muscle cells. Circulation, 30;119:3223-31, 2009.
• Borradaile NM, Pickering JG. Polyploidy impairs human aortic endothelial cell function and is prevented by nicotinamide phosphoribosyltransferase. Am J Physiol Cell Physiol, 298:C66-74, 2010.
• Ho C, van der Veer E, Akawi O, Pickering JG. SIRT1 markedly extends replicative lifespan if the NAD+ salvage pathway is enhanced. FEBS Lett. 17;583:3081-5 2009.
• Small TW, Pickering JG. Nuclear degradation of Wilms tumor 1-associating protein and survivin splice variant switching underlie IGF-1-mediated survival. J Biol Chem, 11;284:24684-95, 2009.
• 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 29:421-7, 2011.