Feng Wu, PhD

University of Western Ontario in Canada, PhD, Phyiology, 2005.

Endothelial barrier dysfunction occurs at every stage of acute lung injury (ALI) in severe sepsis, leading to vascular leakage, edema, and respiratory failure.  Our study for the first time uncovered the existence of NOX2/eNOS uncoupling/Rho signaling pathway, which is involved in the mechanism of endothelial barrier dysfunction. RhoA/ROCK activation causes stress fiber formation and plays a central role in the development of endothelial barrier dysfunction and vascular leakage in ALI. 

Hemorrhagic shock (HS) is the leading cause of the deaths associated with traumatic injuries. One of the primary clinical manifestations of HS is the disruption of the vascular barrier, which leads to microvascular hyperpermeability in vital organs such as the lungs. Clinical studies have shown that early resuscitation with fresh frozen plasma (FFP) is associated with improved outcomes including a survival benefit after trauma/HS. Glycocalyx lines the vascular endothelium and maintains vascular integrity. Our lab found that FFP resuscitation after HS on lung vascular barrier function are associated with restoration of the glycocalyx (syndecan-1).  Recently, we further found that fibrinogen binding prevents MMP9 access to the endothelium, which otherwise cleaves glycocalyx (syndecan-1) and causes lung leakage in mice after hemorrhage shock.

Septic shock, hemorrhage shock, acute lung injury, vascular leakage, endothelial barrier dysfunction, stress fibers, antioxidants, syndecan-1, fibrinogen, miR-19b,

Major academic findings:

1. Vitamin C intravenous injection increases survival in sepsis.

Wu et al. Ascorbate protects against impaired arteriolar constriction in sepsis by inhibiting iNOS expression. Free Radic Biol Med. 2004; 37:1282-1289.

2. miR-19b oligo inhibitors protect the lungs in mice after hemorrhage shock.

Wu et al. miR-19b targets pulmonary endothelial syndecan-1 following hemorrhagic shock. Sci Rep. 2020; 10:15811.

3. Protein gel (fibrinogen) protects vascular integrity in cardiovascular diseases.

Wu et al. Fibrinogen inhibits metalloproteinase-9 activation and syndecan-1 cleavage to protect lung function in ApoE null mice after hemorrhagic shock. J Surg Res 2023; 288:208-214.