Sean E. Gill
PH.D. University of Western Ontario
B.Sc. University of Western Ontario
Office: Centre for Critical Illness Research, Victoria Research Labs, A6-134
p. 519.685.8500 x. 55443
See Publications by Sean Gill on PubMed
Research in my laboratory is currently focused on the resolution of inflammation and repair following lung injury. Lung injury, which leads to acute respiratory distress syndrome (ARDS), is characterized by profound inflammation, edema, and tissue injury often resulting from trauma or severe pulmonary infection. Although ARDS survival rates have improved in recent years, 25 to 40% of cases remain fatal, and of those patients that do survive, persistent inflammation and fibrosis can result in continued pulmonary complications.
Current projects in my lab include assessing the role of metalloproteinases and their endogenous inhibitors, the tissue inhibitors of metalloproteinases (TIMPs) in regulating three different aspects of recovery following lung injury: 1) microvascular endothelial cell dysfunction; 2) macrophage polarization and apoptosis; and, 3) initiation and resolution of fibrosis. Additional projects include examining the role of caspases and cell death in microvascular endothelial cell dysfunction during septic lung injury, as well as determining the effects of aging and exercise on the pathophysiology of lung injury. For these studies, my lab uses multiple murine models of direct lung injury, including bleomycin (a model often used to study chronic lung injury and fibrosis) and Pseudomonas aeruginosa infection, as well as cecal ligation and perforation, a murine model of sepsis that results in indirect lung injury. Techniques such as flow cytometry, immunohistochemistry, quantitative real-time polymerase chain reaction, western blotting, and enzyme activity assays, in combination with culture of isolated primary cells, are then used to examine how specific cell populations are affected during lung injury.
Keywords: MMPs, TIMPs, Lung Injury, Innate Immunity, Resolution of Inflammation, Fibrosis, Apoptosis, Endothelial Cell Dysfunction, Mouse Models
Publications (from the last 5 years)
Masciantonio M.G., Lee C.K.S., Arpino V., Mehta S., and Gill S.E. (2017) The Balance between Metalloproteinases and TIMPs: Critical Mediator of Microvascular Endothelial Cell Function in Health and Disease. Prog Mol Biol Transl Sci. 147:101-131.
Tyml K., Swarbreck S., Secor D., Pape C., Koropatnick J., Feng Q., Veldhuizen R.A.W., and Gill S.E. (2017) Moderate running protects against early sepsis-induced inflammatory response in aged mice. Crit Care. 21(1): 210.
Wang L., Mehta S., Brock M., and Gill S.E. (2017) Inhibition of Pulmonary Microvascular Endothelial Cell Apoptosis Promotes Recovery of Barrier Function Under Septic Conditions. Mediators Inflamm. 2017:3415380.
Arpino V., Mehta S., Wang L., Bird R., Rohan M., Pape C., and Gill S.E. (2016) Tissue inhibitor of metalloproteinases 3-dependent Microvascular Endothelial Cell Barrier Function is Disrupted Under Septic Conditions. Am J Physiol Heart Circ Physiol. 310 (11): H1455-67.
Gill S.E., Yamashita C.M., and Veldhuizen R.A.W. (2016) Lung remodelling associated with the recovery from acute lung injury. Cell Tissue Res. 367(3): 495-509.
Gill S.E., Nadler S.T., Li Q., Frevert C.W., Park P.W., Chen P., and Parks W.C. (2016) Matrilysin (MMP7) Shedding of Syndecan-1/Chemokine Complexes from Epithelium Functions as a Checkpoint of Neutrophil Activation. Am J Respir Cell Mol Biol. 55 (2): 243-251.
Gill S.E., Rohan M., Pape C., and Mehta S. (2015) Role of pulmonary microvascular endothelial cell apoptosis in murine sepsis-induced lung injury in vivo. Respir Res. 16 (1): 109.
Arpino V., Brock M., and Gill S.E. (2015) The role of TIMPs in extracellular matrix proteolysis. Matrix Biol. 44-46: 247-54.
Gill S.E., Taneja R., Rohan M., and Mehta S. (2014) Pulmonary microvascular endothelial cell death during sepsis is neutrophil dependent. PLOS ONE. 9 (2); e88501.
Gill S.E., Gharib S.A., Bench E.M., Sussman S.W., Wang R.T., Rims C., Birkland T.P., Wang Y., Manicone A.M., McGuire J.K., and Parks W.C. (2013) Tissue Inhibitor of Metalloproteinases (TIMP) 3 moderates the pro-inflammatory status of macrophages. Am J Respir Mol Cell Biol. 49 (5): 768-77.
McConnachie L.A., Botta D., White C.C., Weldy C.S., Wilkerson, H-W., Yu J., Dills R., Yu J., Griffith W.C., Faustman E.M., Farin F.M., Gill S.E., Parks W.C., Hu X., Gao X., Eaton D.L., Kavanagh T.J. (2013) The Glutathione Synthesis Gene Gclm Modulates Amphiphilic Polymer-Coated CdSe/ZnS Quantum Dot-Induced Lung Inflammation in Mice. PLOS ONE. 8 (5): e64165.
Wang L., Taneja R., Wang W., Yao L.J., Veldhuizen R.A., Gill S.E., Fortin D., Inculet R., Malthaner R., and Mehta S. (2013) Human alveolar epithelial cells attenuate pulmonary microvascular endothelial cell permeability under septic conditions. PLOS ONE. 8 (2): e55311.
Yamashita C.M., Veldhuizen R.A., and Gill S.E. (2013) Alveolar Macrophages and Pulmonary Surfactant - More than just friendly neighbors. OA Biology. 1 (1): 6.