Research Activities

1. Arterial Remodeling in Development and Disease
I have had a long-standing interest in the transduction of mechanical loads into pathological or physiological arterial remodeling responses. I have developed several animal models to explore arterial remodeling in conditions of altered tensile loading. I was the first to demonstrate a significant tensile strain dependence for arterial smooth muscle survival and the effect of the loss of such dependence on the pathological process of intimal thickening. In collaboration with Dr. Lowell Langille I was able to extend these mechanical studies as well as contribute to an understanding of arterial smooth muscle cell apoptosis during development. I was able to demonstrate, for the first time, a definitive link between activation of the extrinsic pathway of coagulation and inward remodeling of blood vessels. I have more recently extended these studies to include a detailed characterization of the matrix remodeling processes taking place in human abdominal aortic aneurysms and delineated the role of the endothelin pathway in rodent models of abdominal aortic aneurysms.

2. Development of Cardiovascular Biomaterials
I have been involved in the development of novel cardiovascular biomaterials. Most significant have been the acellular matrix scaffolds for arterial and heart valve reconstruction. These natural matrices maintain the inherent mechanical and biological properties of the cardiovascular components from which they are derived, and as such are an ideal tissue engineering scaffold. Indeed many of our extraction techniques have been adopted by industry to produce a new generation of heart valves. I have made significant contributions to the post implantation remodeling and degradation of cardiovascular biomaterials, some of these early studies helped highlight the in vivo degradation of polyurethane grafts. I am currently working with a group at Oregon Biomedical Engineering Institute (Portland, Oregon) on the development of recombinant human elastin based biomaterials for cardiovascular repair, the favorable viscoelastic behaviour of such materials makes them promising candidates for use in repair of the cardiovascular system. More recently I have developed cell encapsulation technology to promote cell survival during cell processing and delivery to the tissue of interest. In addition the capsules are designed to promote cell release and tissue engraftment.

3. Cell Based Therapies for the Treatment of Cardiovascular Disease
For the past six years I have been working on the development of cell based therapies for cardiovascular diseases. I am leading a translational program in cell based gene therapy at the Ottawa Hospital Research Institute. I am overseeing the production of genetically transfected autologous endothelial progenitor cells for two multi-center clinical trials. The PHACeT trial is a first in man study, run in Montreal and Toronto, we have used these cells to target regeneration of the pulmonary vasculature in patients suffering from primary pulmonary hypertension, early results in three patients have been very promising. ENACT is randomized controlled trial, run in Ottawa, Montreal, and Toronto, in this trial we will be treating patients after a heart attack by intracoronary infusion of the cell product. We have recently received CIHR funding for a trial treating acutely ill septic patients in the intensive care unit; for this trial I will oversee processing of allogenic mesenchymal stromal cells.

4. Development of cGMP Facilities and Processes for Cellular Therapy
To facilitate the clinical trials I have designed and built two novel cGMP processing facilities (Toronto and Ottawa). The Ottawa facility incorporates uniquely designed isolator technology to speed work-flow, limit costs, and increase product safety. In addition these isolators allow for the precise and continuous regulation of gas pressures and temperature allowing for the production of a consistent cell product. I have also developed novel methods of transient cell transfection, enhancing cell therapeutic function that can be applied in the cGMP processing.