Understanding mechanisms of ischemia-reperfusion (IR) injury after lung transplantation such as vascular inflammation, diagnosis via molecular imaging, and identifying therapeutic targets for the prevention or treatment of IR injury.
My laboratory conducts translational studies into mechanisms and prevention of lung ischemia-reperfusion (IR) injury following transplantation. IR injury is a rapid and robust inflammatory response that leads to increased morbidity and mortality after lung transplant. Our research utilizes both in vivo and in vitro models to explore inflammatory signaling pathways in innate immune cells, alveolar epithelial cells and vascular endothelial cells as well as cross-talk among these cells. One NIH-funded project is aimed at defining the role of pannexin 1 (Panx1)-derived extracellular ATP in mediating lung IR injury through activation of endothelial cells, neutrophils, and alveolar macrophages via purinergic signaling pathways. A second NIH-funded project is the development of novel molecular imaging probes (to target specific cells such as neutrophils or M1 and M2 macrophages) for non-invasive PET and SPECT imaging in order to provide early diagnosis of lung IR injury and to permit early therapeutic intervention. A third NIH-funded project utilizes the novel technique of ex vivo lung perfusion (EVLP) in which injured donor lungs undergo ex vivo perfusion in order to assess function prior to transplantation. We are testing various protective, anti-inflammatory treatments during EVLP to recondition injured donor lungs and prevent graft failure after transplantation. Other projects in the lab include: 1) understanding the resolution of lung IR injury and how we can augment this protective pathway in transplanted lungs, 2) studying the role of NADPH oxidase (NOX2)-derived superoxide production in the activation of various pulmonary cell types during IR injury, and 3) defining the role of calcium uptake by various cells via TRPV4 channels during lung IR injury.