Research Interests

The major focus of my research is the regulation of endothelial activation in systemic sepsis and localized pneumonia. Endothelial activation is a necessary step in the recruitment of leukocytes (e.g., neutrophils) from the bloodstream to combat systemic infections.

My research targets the pathophysiological processes that cause potentially lethal lung edema following systemic (i.p.) bacterial infection. I monitor the experimentally-infected animals using techniques drawn from molecular biology, biochemistry, and physiology. My results show that the principal cause of lung edema during sepsis is increased pulmonary vascular permeability. Multiple factors appear to be involved, including pro-inflammatory cytokines, chemokines, and bacterial products, which in turn induce interendothelial gaps, expression of neutrophil-endothelial cell adhesion molecules (e.g., CD18, ICAM-1), and high levels of oxidant generation. I have developed an ex vivo perfused and isolated mouse lung model in which vascular permeability, neutrophil migration, and oxidant generation can be measured to evaluate lung injury. I am comparing sepsis-induced lung injury in several knockout mouse models. Information gained from mouse models may lead to novel strategies to reduce lung injury and multi-organ system failure during sepsis.

• Rubinstein I, Potempa J. Travis J, Gao XP. Mechanisms mediating prophyromonas gingivalis gingipain RgpA-induced oral mucosa inflammation in vivo. Infect Immun 2001 Feb;69(2):1199-1201.


• Xiaopei Gao, Panos Kouklis, Ning Xu, Richard D. Minshall, Raudel Sandoval, Stephen M. Vogel and Asrar B. Malik. Increased microvessel permeability and its reversibility in mouse lung in response to VE-Cadherin disassembly and reassembly. Am J Physiol Lung Cell Mol Physiol. 2000 Dec;279(6):L1218-25.


• S.M. Vogel, Xiaopei Gao, D. Metha, R.D. Ye, C. T.A. John. P. Andrade-Gordon, C. Tiruppathi, and A. B. Malik. Abrogation of thrombin-induced increase in pulmonary microvascular permeability in PAR-1 knockout mice. Physiol. Genomics, 2000 Dec 18:4(2):137-145.


• Xiao-pei Gao, Syed R. Akhter, Hiroyuki Ikezaki, Dennis Hong, and I. Rubinstein. Dexamethasone attenuates the acute increase in macromolecular efflux evoked by smokeless tobacco extract. J. Appl. Physiol. 87(2): 619-25, 1999.