The Zhao lab studies the molecular mechanisms of endothelial injury and regeneration, resolution of inflammation, and obliterative vascular remodeling in the pathogeneses of sepsis, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and pulmonary arterial hypertension (PAH).
Recovery of endothelial barrier integrity after vascular injury is vital for endothelial homeostasis and resolution of inflammation. Endothelial dysfunction plays a critical role in the initiation and progression of vascular diseases such as ALI/ARDS and atherosclerosis. A part of the research in the lab, employing genetically modified mouse models of human diseases, endothelial progenitor cells/stem cells, and translational research approach as well as nanotechnology, is to elucidate the molecular mechanisms of endothelial regeneration and resolution of inflammatory injury and determine how aging and epigenetics regulate these processes (J. Clin. Invest. 2006, 116: 2333; J. Exp. Med. 2010, 207:1675; Circulation 2016, 133: 2447). We are also studying the role of endothelial cells in regulating macrophage functional polarization and resolving inflammatory lung injury. These studies will identify druggable targets leading to novel therapeutic strategies to activate the intrinsic endothelial regeneration program to restore endothelial barrier integrity and reverse edema formation for the prevention and treatment of ARDS in patients.
Pulmonary arterial hypertension (PAH) is a progressive disease with poor prognosis and high mortality. We are currently investigating the molecular basis underlying the pathogenesis. We have recently identified the first murine model of PAH with obliterative vascular remodeling including vascular occlusion and formation of plexiform-like lesions resembling the pathology of clinical PAH (Circulation 2016, 133: 2447). Our previous studies also show the critical role of oxidative/nitrative stress in the pathogenesis of PAH as seen in patients (PNAS 2002, 99:11375; J. Clin. Invest. 2009, 119: 2009). With these unique models and lung tissue and cells from idiopathic PAH patients, we will define the molecular and cellular mechanisms underlying severe/obliterative vascular remodeling and provide novel therapeutic approaches for this devastating disease.
Current Research Projects
The Zhao lab employs the state-of-the art technologies including genetic lineage tracing, genetic depletion, genetic reporter, and CRISPR-mediated in vivo genomic editing as well as patient samples to study the molecular mechanisms of sepsis, acute lung injury/ARDS, and pulmonary arterial hypertension and identify novel therapeutics for these devastating diseases. Current studies include 1) molecular mechanisms of endothelial regeneration and vascular repair following inflammatory lung injury induced by sepsis and penumonia; 2) how aging and epigenetics regulate this process; 3) how endothelial cells regulate macrophage and neuptrophil function for resolution of inflammation and host defense; 4) stem/progenitor cells in acute lung injury and pulmonary hypertension and cell-based therapy; 5) mechanisms of obliterative pulmonary vascular remodeling; 6) molecular basis of right heart failure; 7) pathogenic role of oxidative/nitrative stress; 8) lung regeneration; 9) drug discovery; 10) nanomedicine.
Zhiyu Dai, PhD Research Assistant Professor
Xianming Zhang, PhD Research Assistant Professor
Narsa Machireddy, PhD Research Assistant Professor