Pediatrics / Fazal Lab / Endoplasmic reticulum BiP & Mitochondrial GRP75 Proteins in Acute Lung Injury
Project 1:
Understanding the role of endoplasmic reticulum (ER) protein BiP and mitochondrial protein GRP75 in the pathogenesis of acute lung injury (ALI)
Our first project involves understanding the role of endoplasmic reticulum (ER) protein BiP and mitochondrial protein GRP75 in the pathogenesis of acute lung injury (ALI).
Since the crosstalk between cellular organelles is critical to cellular homeostasis, our second area of research involves understanding the role of endoplasmic reticulum (ER) and mitochondrial unit in ALI. We have identified ER chaperone BiP and mitochondrial chaperone mortalin as critical players in mediating EC dysfunction induced by procoagulant and proinflammatory mediator thrombin and bacterial and environmental endotoxin lipopolysaccharide (LPS). We use LPS inhalation and LPS-induced sepsis mouse models to address the in vivo significance of these molecules in the pathogenesis of ALI. By better understanding the precise molecular mechanisms controlling the infiltration of PMN into the lung, it would be possible to selectively target specific signaling molecule(s) in order to suppress the detrimental lung PMN influx and vascular leak associated with ALI.
