At his Thoracic Surgery Research Laboratory, Kehavjee's research interests include lung transplantation, lung injury, and lung preservation. His current studies examine molecular diagnostics and gene therapy strategies for engineering organs for lung transplantation. The Lab's work explores the underlying mechanisms of ischemia-reperfusion injury and bronchiolitis obliterans – two areas that limit successful lung transplantation – and develops gene therapy strategies for either preventing or reversing them. Several areas within ischemia-reperfusion injury are examined, including the role of complement and cytokine-related lung injury and its relation to reperfusion. The work is done on
cell culture models, rat single lung transplant models, and pig single lung transplant models.
Lung preservation Keshavjee and his research team have developed a technique of lung preservation that can improve lung function after its transplantation. The solution is made from low-potassium dextran and is used in the
Ex Vivo. The LPD solution is applied in both the Toronto lung transplant program and in clinical programs around the world.
Gene therapy in lung transplantation Keshavjee's research team focuses its main efforts on the role of gene therapy in lung transplantation. They are currently developing techniques for genetically modifying the donor lung so it can withstand stress during the transplant process. Ultimately, these techniques would be used to address both ischemia-reperfusion injury and obliterative bronchiolitis. Keshavjee's work has demonstrated that immunosuppression related to transplantation leads to an altered expression of the transgene, and immunosuppression will lead to the prolonged-expression of the transgene. To this effect, he and his team have proved that gene therapy will help recipients recover from lung transplantation surgery without a significant immune system response. When addressing obliterative bronchiolitis in a rat tracheal transplant model of fibrous airway obliteration related to transplantation, Keshavjee's research showed that the adenoviral IL-10 gene transfection was able to prevent the development of bronchiolitis obliterans. This was the first time that a gene therapy strategy was able to treat this condition; a significant breakthrough as this condition affects over 50% of lung transplant recipients. The team is currently studying the effect of the IL-10 transfection on ischemia-reperfusion therapy, as well as mechanisms of cell death and the genes controlling the process. ==Toronto Lung Transplant Program==