Within the regenerative medicine and global health platforms, investigation takes place along the value chain for molecular and cellular response and repair via a process of discovery that proceeds from characterization to translation to validation. Characterization is fundamental—scientists at the Centre for Molecular and Cellular Response and Repair (CMCRR) apply genomic and proteomic analyses toward elucidation of the genetic instability that gives rise to disease and the corresponding biomarkers of disease and disease progression. Translation and validation are as essential, as mechanisms for validating biomarkers and targets, and assigning predictive value to them in the context of disease progression and response to experimental therapies. Dedicated to this cohesive approach to disease, CMCRR scientists maintain research programs that are distinct yet overlap, to advance the collaborative aims of the centre.

Charles Cunningham
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Dr. Cunningham, a physical sciences scientist in the Schulich Heart Research Program at Sunnybrook Research Institute (SRI), is developing new methods for metabolic/molecular imaging in regenerative medicine. Other work includes collaboration with fellow CMCRR scientist Dr. Bradley Strauss to develop a method for imaging the release of drugs from microspheres that can be implanted in blocked blood vessels, with the aim of improving treatment and outcomes. Together with Dr. Alexander Dick, they developed a new method to track implanted progenitor cells that have the potential for visualizing the fate of single cells.

Alexander Dick
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Dr. Dick is conducting a clinical trial examining the safety and efficacy of eNOS-transfected endothelial progenitor cells (EPCs) in heart repair and regeneration after myocardial infarction. A clinician-scientist in the Schulich Heart Research Program and physical sciences platform at SRI, Dick, with postdoctoral fellow Dr. John Graham, has also developed a reproducible model of reperfusion (restored blood flow) post-myocardial infarction in swine, to test and develop eNOS-transfected EPC therapy. With postdoctoral fellow Dr. Warren Foltz, Dick is testing new MRI off-resonance positive contrast techniques to quantify cell number after delivery. Finally, with other collaborators, he is examining the intrinsic contrast provided by agarose encapsulation of stem cells, which may provide a useful way to monitor noninvasively the release and, potentially, engraftment of cells in vivo.

Dan Dumont
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Dr. Dumont studies the molecular fundamentals of angiogenesis and lymphangiogenesis (lymphatic vessel formation). Focusing on development of the cardiovascular system of the mouse embryo, Dumont and his lab are aiming to shed light on how to control tumour growth and the progression of type 1 diabetes. They are also studying the function of the Tek/Tie2 cell surface receptor (important in blood vessel regeneration), and have identified and characterized this receptor’s signaling modality. Dumont and his lab have also developed and patented a new therapeutic for chronic wound care, and are using a proteomic and animal physiological approach to study the role of growth factors in the lymphangiogenic response for applications in regenerative medicine. Dumont is a senior scientist in biological sciences at SRI and the Canada Research Chair in Angiogenic and Lymphangiogenic Signalling.

Bradley Strauss
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Dr. Strauss is a senior scientist in the platform of biological sciences at SRI and the director of interventional cardiology research in the Schulich Heart Program at Sunnybrook, where he is also a clinician. His research focuses on chronic total occlusions (CTOs), and he has developed several animal models of CTOs, for his research and for companies testing novel devices to treat them. Strauss recently pioneered a unique therapy for CTOs in animals, which involves injecting the enzyme collagenase to soften artery-blocking collagen, thereby allowing surgeons to perform angioplasty much more easily (traditional success rates for angioplasty in CTOs are about 50%). Strauss will begin the first clinical trial of this new technique with colleagues at Sunnybrook and St. Michael’s Hospital in 2008.

Graham Wright
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Dr. Wright and his lab study basic biophysics to characterize the relationship between magnetic resonance imaging (MRI) signals and underlying physiology in blood and tissue. They also research ways to engineer more effective methods to acquire, analyze, and visualize medical images. In collaboration with other CMCRR scientists, they are applying these imaging tools to assessment, treatment planning and therapy guidance in ischemic and congenital heart diseases, and in neurovascular and peripheral vascular diseases. Wright and his lab have extended the design of devices for catheter-based imaging with MRI, as well as the design of a real-time acquisition and visualization system to facilitate image-guided interventions in cardiovascular diseases. Wright is a senior scientist in physical sciences at SRI and the director of SRI’s Schulich Heart Research Program.

Juan Carlos Zúñiga-Pflücker
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Dr. Zúñiga-Pflücker’s work seeks to identify the molecular interactions that regulate T cell differentiation, a process that takes place in the thymus, in which hematopoietic stem cells become mature, disease-fighting T cells. Having developed a unique in vitro system that replicates the full range of T cell development, Zúñiga-Pflücker and his lab are exploiting that system via flow cytometry, scanning microscopy and other molecular biology techniques to map the precise molecular conditions required for healthy T cell production. T cells generated in vitro have the potential for therapeutic use to treat people whose immune systems have been devastated by disease or the toxicity of certain treatments (e.g., chemotherapy). Zúñiga-Pflücker is a senior scientist in biological sciences biology at SRI and the Canada Research Chair in Developmental Immunology.