Lung Transplant Research Projects
Some of our current research projects are outlined below (click on title below or in left menu for details).
Role of T cells and IL-17 in lung IR injury. CD4+ T cells are key initiators of lung IR injury. This project tests the overall hypothesis that IR injury is initiated through iNKT cell activation via production of IL-17 and NADPH oxidase-dependent oxidative stress.
Role of dendric cells and IL-23/IL-12 in lung IR injury. We have found the dendric cells (DCs) are also rapidly activated after IR and that IL-23 and IL-12 levels are increased. We are currently evaluating the role of DCs and DC-produced IL-23 and IL-12 in the initiataion of IR injury.
Role of adenosine receptors in lung IR injury. One anti-inflammatory mechanism involves adenosine production which acts through four adenosine receptors: A1, A2A, A2B, and A3. This project tests the role of each adenosine receptor in lung IR injury using an in vivo muring model.
The receptor for advanced glycation end products (RAGE) is a ubiquitous, multiligand receptor implicated in a variety of pathological conditions such as diabetes and its complications, cancer, cardiovascular disease and inflammation. We are studying the role of RAGE signaling via HMGB1 in lung IR injury.
Porcine ex vivo lung perfusion (EVLP) & transplant. This project uses EVLP as a platform for pharmacologic delivery of A2AR agonist to test the overall hypothesis that EVLP with concomitant A2AR agonist treatment will prevent IR injury and rehabilitate non-heart beating donor (NHBD) lungs. The advantage of this porcine model is that we can then transplant lungs after EVLP and assess post-transplant graft function and inflammation.
Human EVLP. In addition to the porcine EVLP & transplant model, we are also studying the rehabilitating marginal human donor lungs via EVLP.
Protection of transplanted lungs by adenosine A2A receptor activation. This project, using a pig lung transplant model, tests the hypothesis that adenosine A2A receptor activation in the donor lung or in combination with other receptor agonists provides superior protection from IR injury.
Transplantation immunology. Our lab studies mechanisms of cardiothoracic transplant rejection with a current focus on adenosine signaling. We use various models including murine heterotopic and orthotopic tracheal transplant models of chronic rejection, an orthotopic heart transplant model, and the left lung hilar clamp model of lung IR injury.
Stem cell therapy. We have begun studies into the therapeutic potential of mesenchymal stem cells to inhibit lung IR injury, rehabilitate marginal donor lungs via EVLP, and reduce the incidence of bronchiolitis obliterans.