Sean E. Gill

Assistant Professor

PH.D. University of Western Ontario
B.Sc. University of Western Ontario
Office:  Centre for Critical Illness Research, Victoria Research Labs, A6-134
Phone: (519) 685-8500 Ext 55443
Fax: (519) 685-8341
E-mail: sgill8@uwo.ca
See Publications by Sean Gill on PubMed

Research in my laboratory focuses on the resolution of inflammation and fibrosis following lung injury. Acute lung injury (ALI) is characterized by profound inflammation and tissue injury often resulting from trauma or severe pulmonary infection. Although ALI 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. We determined that tissue inhibitor of metalloproteinases 3 (TIMP3) serves to restrict ongoing neutrophil influx during the repair process, and is thereby integral to the resolution of inflammation. Additionally, we have demonstrated that fibrosis is enhanced following lung injury in the absence of TIMP3, which suggests that TIMP3 moderates the fibrotic response.

To establish the mechanisms through which TIMP3 mediates resolution of inflammation and fibrosis following lung injury, we utilize both in vivo and in vitro techniques. My lab uses multiple 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 model of sepsis that results in indirect lung injury. These models are performed on wild type (or control mice) and mice lacking TIMP3 (Timp3-/- mice). Techniques such as flow cyotemetry and immunohistochemistry are then used to examine how specific cell populations are affected by the presence or absence of TIMP3 during lung injury. Current work is focused on understanding the role that TIMP3 has in controlling macrophage function and apoptosis following ALI.

Kim T., Chow Y., Gill S.E., and Schnapp L.M. (2012) Effect of IGF blockade on hyperoxia-induced lung injury. Am J Respir Cell Mol Biol. In Press.

Tanino Y., Chang M.Y., Wang X., Gill S.E., Skerrett S., McGuire J.K., Sato S., Nikaido T., Kojima T., Munakata M., Mongovin S., Parks W.C., Martin T.R., Wight T.N., and Frevert C.W. (2012) Syndecan-4 Regulates Early Neutrophil Migration and Pulmonary Inflammation in Response to Lipopolysaccharide. Am J Respir Cell Mol Biol. In Press.

Schrimpf C., Xin C., Campanholle G., Gill S.E., Stallcup W., Lin S.L., Davis G.E., Gharib S.A., Humphreys B.D., and Duffield J.S. (2012) Pericyte TIMP3 and ADAMTS1 Modulate Vascular Stability after Kidney Injury. J Am Nephrol. In Press.

Weldy C.S., White C.C., Wilkerson H., Larson T.V., Stewart J.A., Gill S.E., Parks W.C., and Kavanagh T.J. (2011) Heterozygosity in the Glutathione Synthesis Gene Gclm Increases Sensitivity to Diesel Exhaust Particulate Induced Lung Inflammation in Mice. Inhal Toxicol. 23(12): 724-35.

Van den Berg E., van Woensel J.B.M., Bos A.P., Bem R.A., Altemeier W.A., Gill S.E., Martin T.R., and Matute-Bello G. (2011) Role of the Fas/FasL system in a model of RSV infection in mechanically ventilated mice. Am J Physiol Lung Cell Mol Physiol. 301(4): L451-60.

Gill S., Wight T.N., and Frevert C.W. (2010) Proteoglycans: Key Regulators of Pulmonary Inflammation and the Innate Immune Response to Lung Infection. Anat Rec (Hoboken). 293(6): 968-81.

Hu J.H., Du L., Chu T., Otsuka G., Dronadula N., Jaffe M., Gill S.E., Parks W.C., and Dichek D.A. (2010) Overexpression of urokinase by plaque macrophages causes histologic features of plaque rupture and increases vascular MMP activity in older apoE-null mice. Circulation. 121(14): 1637-44.

Tanino Y., Coombe D.R., Gill S.E., Kett W.C., Kajikawa O., Proudfoot A.E.I., Wells T.N.C., Wight T.N., Martin T.R., and Frevert C.W. (2010) Kinetics of Chemokine-Glycosaminoglycan Interactions Control Neutrophil Migration into the Airspaces of the Lungs. J Immunol. 184(5): 2677-85.

Gill S.E., Huizar I., Bench E.M., Sussman S.W., Wang Y., Khokha R., and Parks W.C. (2010) Tissue inhibitor of metalloproteinases 3 regulates resolution of inflammation following acute lung injury. Am J Pathol.176 (1): 64-73.

Gill S.E., Pape M.C., and Leco K.J. (2009) Absence of tissue inhibitor of metalloproteinases 3 disrupts alveologenesis in the mouse. Dev Growth Differ. 51(1): 17-24.

Gill S.E. and Parks W.C. (2008) Metalloproteinases and their inhibitors: Regulators of wound healing. Int J Biochem Cell B. 40: 1334-1347.






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