My project focuses on endothelial cell-specific mediators, Angiopoietins 1 & 2, and their role in the vascular dysfunction observed in the development of acute lung injury (ALI).

Research Description

My project focuses on endothelial cell-specific mediators, Angiopoietins 1 & 2, and their role in the vascular dysfunction we observe in the development of acute lung injury (ALI). Under physiological conditions, expression of these 2 proteins and their interaction with their shared receptor, Tie2, is tightly regulated. However, in trauma patients and in our shock/sepsis mouse model for the development of ALI, Ang-2 in significantly up-regulated, deleteriously impacting vascular integrity (increased micro-vascular permeability and edema). The aims of my project are to determine the kinetics of Ang-2/Ang-1 change in expression and begin to unravel the mechanisms (cellular and/or molecular) that precipitate loss of pulmonary endothelial barrier function in the development of ALI.

Awards

Rhode Island FoundationMedica Research Grant 2010-2011
Surgical Infection Society Junior Faculty Fellowship 2011-2012

Selected Publications

• Monaghan, S.F., Thakkar, R.K., Heffernan, D.S., Tran, M.L., Huang, X., Chung, C.S., Chen, Y., Lomas-Neira, J.L., Cioffi, W.G., Ayala, A. 2011. Mechanisms of indirect acute lung injury: a novel role for the co-inhibitory receptor, programmed death-1 (PD-1). Ann. Surg. (in press). (PMID: 21997806)(2011)
• Perl, M., Lomas-Neira, J.L., Venet, F., Chung, C.S., Ayala, A. 2011. Pathogenesis of indirect (secondary) acute lung injury (ALI). Expert Rev. Resp. Med. 5:115-126. (REVIEW; PMID: 21348592).(2011)
• Perl, M., Chung, C.S., Perl, U., Thakkar, R., Lomas-Neira, J.L., Ayala, A. 2010. Therapeutic accessibility of caspase mediated cell death as a key patho-mechanism in indirect acute lung injury. Crit. Care. Med. 39:1179-86. (PMID: 0154604). (2010)
• Venet, F., Chung, C.S., Huang, X., Lomas-Neira, J.L., Chen, Y., Ayala, A. 2009. Indirect lung injury: a role for regulatory T lymphocytes in the development of pulmonary inflammation. J. Immunol. 183:3472-80 (PMID: 19641139). (2009)
• Lomas-Neira, J.L., Chung, C.S., Ayala, A. 2008. RNA interference as a potential therapeutic treatment for inflammation associated lung injury. Inter. J. Clin. Exp. Med. 1:154-160 (REVIEW; PMID: 19079669).(2008)
• Perl, M., Lomas-Neira, J.L., Chung, C.S., Ayala, A. 2008. Epithelial apoptosis and neutrophil recruitment in acute lung injury - A unifying hypothesis? What we have learned from small interfering RNAs. Mol. Med. 14:465-475 (REVIEW; PMID: 18368145).(2008)
• Huang, X., Venet, F., Lomas-Neira, J.L., Chung, C.S., Ayala, A. 2007. Changes in dendritic cell function in the immune response to sepsis. Expert Opin. Biol. Ther. 7:929-938 (REVIEW; PMID: 17665984).(2007)
• Perl, M., Chung, C.S., Perl, U., Lomas-Neira, J.L., De Paepe, M., Cioffi, W.G., Ayala, A. 2007. Fas induced pulmonary apoptosis and inflammation during indirect acute lung injury. Amer. J. Resp. & Crit. Care. Med. 176:591-601 (PMID: 17600273).(2007)
• Chung, C.S., Watkins, L., Song, G.Y., Lomas-Neira, J.L., Cahoone, E.V., Cioffi, W.G., Ayala, A. 2006. Deficiency in gamma-delta T-lymphocytes compromises the ability of mice to survive polymicrobial sepsis. Amer. J. Physiol. 291:R1338-1343 (PMID:16878028).(2006)
• Lomas-Neira, J.L., Chung, C.S., Perl, M., Gregory, S., Biffl, W., Ayala, A. 2006. Role of alveolar macrophage & migrating neutrophils in hemorrhage induced priming for ALI subsequent to septic challenge. Amer. J. Physiol. 290:51-58 (PMID: 16157517).(2006)
• Wesche, D.E., Lomas-Neira, J.L., Perl, M., Chung, C.S., Ayala, A. 2005. Leukocyte apoptosis and its significance in sepsis and shock. J. Leukocyte Biol. 78:325-337 (REVIEW; PMID: 15817707).(2005)
• Lomas-Neira, J.L., Perl, M., Chung, C.S., Ayala, A. 2005. Shock and hemorrhage: An overview of animal models. Shock 24 (Suplt. 1): 33-39 (REVIEW; PMID: 16374370).(2005)
• Perl, M., Chung, C.S., Lomas-Neira, J.L., Rachel, T.M., Biffl, W.L., Cioffi, W.G., Ayala, A. 2005. Silencing of Fas- but not caspase-8 in lung epithelial cells ameliorates experimental acute lung injury. Amer. J. Pathol. 167:1545-559 (PMID: 16314469).(2005)
• Wesche-Soldato, D.E., Chung, C.S., Lomas-Neira, J.L., Doughty, L.A., Gregory S. H., Ayala, A. 2005. In vivo delivery of caspase 8 or FAS siRNA impoves the survival of septic mice. Blood. 106:2295-2301 (PMID: 15941915).(2005)
• Lomas-Neira, J.L., Chung, C.S., Wesche, D.E., Perl, M., Ayala, A. 2005. In vivo gene silencing (with siRNA) of pulmonary expression of MIP-2 vs. KC results in divergent effects on hemorrhage induced neutrophil mediated septic acute lung injury. J. Leukocyte Biol. 77:846-853 (PMID: 15695553).(2005)
• Lomas-Neira, J.L., Chung, C.S., Grutkoski, P.S., Miller, E.J., Ayala, A. 2004. CXCR2 inhibition suppresses hemorrhage induced priming for acute lung injury in mice. J. Leukoc. Biol. 76:58-64 (PMID: 15123771).(2004)
• Rhee, R.J., Carlton, S., Lomas, J.L., Lane, C., Brossay, L., Ayala, A. 2003. Inhibition of CD1d activation suppresses septic mortality: a role for NK-T cells in septic immune dysfunction. J. Surg. Res. 115:74-81 (PMID: 14572776).(2003)
• Lomas, J.L., Chung, C.S., Grutkoski, P.S., LeBlanc, B.W., Lavigne, L., Reichner, J., Gregory, S.H., Doughty, L.A., Cioffi, W.G., Ayala, A. 2003. Differential effects of MIP-2 and KC on hemorrhage induced neutrophil priming for lung inflammation: assessment by adoptive cell transfer in mice. Shock 19:358-365 (PMID: 12688548).(2003)
• Chung, C.S., Song, G.Y., Lomas, J.L., Simms, H.H., Chaudry, I.H., Ayala, A. 2003. Inhibition of Fas/Fas ligand (FasL) signaling during sepsis has tissue specific effects on macrophage apoptotic and functional capacity. J. Leukocyte Biol. 74:344-351 (PMID: 12949237)(2003)
• Ayala, A., Chung, C.S., Lomas, J.L., Song, G.Y., Doughty, L.A., Gregory, S.H., Cioffi,W.G., LeBlanc, B.W., Reichner, J., Simms, H.H., Grutkoski, P.S. 2002. Shock induced neutrophil mediated priming for acute lung injury in mice: divergent effects of TLR-4 and TLR-4/FasL deficiency. Amer. J. Pathology 161:2283-2294 (PMID: 12466142).(2002)