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 studies mechanisms and prevention of lung ischemia-reperfusion (IR) injury following transplantation. IR injury is a 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 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 project is the development of novel molecular imaging probes (to target specific cell populations) for non-invasive PET or SPECT imaging in order to provide early diagnosis of lung IR injury. 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.