Our laboratory investigates the molecular mechanisms of lung ischemia-reperfusion injury (IRI), and focuses on identifying therapeutic strategies to prevent IRI after lung transplantation. Our studies explore the role of myeloid-derived suppressor cells (MDSCs), innate immune cells, alveolar epithelial cells, and endothelial cells. Therapeutic options include mesenchymal stem cell-derived extracellular vesicles and pro-resolving specialized lipid mediators in the mitigation of lung IRI. Ongoing research projects are summarized below:
- Mesenchymal stem cell-derived extracellular vesicles in mitigation of lung ischemia-reperfusion injury and enhancement of donor lung rehabilitation. The focus of this project is to delineate the protective role of mesenchymal stem cells and its derivatives (extracellular vesicles) in the attenuation of lung IR injury via regulation of specific microRNAs. Moreover, supplementation of ex vivo lung perfusion with modified microvesicles is postulated to enhance rehabilitation of DCD (donation after cardiac death) lungs.
- Immunomodulation of lung IRI by myeloid-derived suppressor cells via CXCR2 dependent signaling. Contribution of innate immune cell population of MDSC subsets and their recruitment to the lung after IRI through chemokine receptor CXCR2 expressed on circulating myeloid or pulmonary vascular endothelium will be deciphered using transgenic mice. Our central hypothesis is that MDSCs demonstrate an immunosuppressive phenotype via modulation of IL-10/IL-17 axis in Treg-iNKT cell crosstalk to attenuate early post-lung transplant IRI.
- Resolution of lung IRI by specialized pro-resolving mediators mitigates primary graft dysfunction. We are investigating the role of w-3 fatty acid derived SPMs i.e. Resolvins and Maresins, in the immunomodulation of macrophage phenotype and enhanced efferocytosis in the attenuation of pulmonary inflammation and resolution of primary graft dysfunction.
- Novel role of TRPV4/eNOS signaling in endothelial permeability regulation during lung transplant injury. The aim of this project is to pinpoint the contributory role of calcium sensitive transient receptor potential vanilloid 4 (TRPV4) channels on the pulmonary endothelium to regulate leukocyte trafficking during lung transplant injury.