The overall goals of our research are to investigate the pathogenesis and therapeutic interventions in environmentally-induced lung inflammation and scarring (also called fibrosis)

• Project 1: Construction and use of adenovirus gene transfer vectors for use in lung diseases We are constructing recombinant adenovirus vectors for delivery of cytokine genes to lung tissues. The purpose is to analyze the functions of these genes in lung inflammation and scarring which are the basis of many environmental lung diseases such as coal workers pneumoconiosis, silicosis and asbestosis. In addition we are developing targets to block these same mediators, and so develop gene therapies for lung diseases. Students would be involved in constructing recombinant adenoviruses as gene delivery tools, and using these in animal models of lung diseases induced by toxicants such as silica, and thoracic irradiation.
• Project 2: Examination of the ability of cigarette smoke and diesel exhaust particles to enhance asthmatic responses in a mouse model of asthma Asthma is an inflammatory disease of the airways, but the pathogenesis is not well understood. However, the cell signaling molecules called type 2 cytokines appear important. Both cigarette smoking and diesel exhaust have been implicated in the generation of asthma and itÍs increasing incidence. This project will examine the ability of both smoke and diesel to enhance allergic asthmatic responses in a model of asthma in mice. Students involved in this project would use animal pre-clinical models, cell culture and molecular probe techniques, flow cytometry and histological evaluations to test the hypothesis that smoke and diesel exacerbate type 2 responses and allergic airways inflammation.

Recent Publications

O’Reilly KM, Mclaughlin AM, Beckett WS, Sime PJ. 2007. Asbestos-related lung disease. Am Fam Physician. Mar 1;75(5):683-688.

Thatcher TH, Maggirwar SB, Baglole CJ, Lakatos HF, Gasiewicz TA, Phipps RP, Sime PJ. 2007. Aryl hydrocarbon receptor-deficient mice develop heightened inflammatory responses to cigarette smoke and endotoxin associated with rapid loss of the nuclear factor-kappaB component RelB. Am J Pathol. Mar;170(3):855-864.

Shah AP, Xu H, Sime PJ, Trawick DR. 2006. Severe airflow obstruction and eosinophilic lung disease after Stevens-Johnson syndrome. Eur Respir J. Dec;28(6):1276-1279.

Baglole CJ, Ray DM, Bernstein SH, Feldon SE, Smith TJ, Sime PJ, Phipps RP. 2006. More than structural cells, fibroblasts create and orchestrate the tumor microenvironment. Immunol Invest. 35(3-4):297-325. Review.

Lakatos HF, Burgess HA, Thatcher TH, Redonnet MR, Hernady E, Williams JP, Sime PJ. 2006. Oropharyngeal aspiration of a silica suspension produces a superior model of silicosis in the mouse when compared to intratracheal instillation. Exp Lung Res. May;32(5):181-199.

Viscardi RM, Atamas SP, Luzina IG, Hasday JD, He JR, Sime PJ, Coalson JJ, Yoder BA. 2006. Antenatal Ureaplasma urealyticum Respiratory Tract Infection Stimulates Proinflammatory, Profibrotic Responses in the Preterm Baboon Lung. Pediatr Res. Aug;60(2):141-146.

Baglole CJ, Bushinsky SM, Garcia TM, Kode A, Rahman I, Sime PJ, Phipps RP. 2006. Differential induction of apoptosis by cigarette smoke extract in primary human lung fibroblast strains: implications for emphysema. Am J Physiol Lung Cell Mol Physiol. Jul;291(1):L19-29.

Thatcher TH, Sime PJ, Barth RK. 2005. Sensitivity to bleomycin-induced lung injury is not moderated by an antigen-limited T-cell repertoire. Exp Lung Res. Sep;31(7):685-700.

Baglole CJ, Reddy SY, Pollock SJ, Feldon SE, Sime PJ, Smith TJ, Phipps RP. 2005. Isolation and phenotypic characterization of lung fibroblasts. Methods Mol Med. 117:115-127.

Martey CA, Baglole CJ, Gasiewicz TA, Sime PJ, Phipps RP. 2005. The aryl hydrocarbon receptor is a regulator of cigarette smoke induction of the cyclooxygenase and prostaglandin pathways in human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. Sep;289(3):L391-399.

Thatcher TH, McHugh NA, Egan RW, Chapman RW, Hey JA, Turner CK, Redonnet MR, Seweryniak KE, Sime PJ, Phipps RP. 2005. Role of CXCR2 in cigarette smoke-induced lung inflammation. Am J Physiol Lung Cell Mol Physiol. Aug;289(2):L322-328.

Vallance BA, Gunawan MI, Hewlett B, Bercik P, Van Kampen C, Galeazzi F, Sime PJ, Gauldie J, Collins SM. 2005. TGF-beta1 gene transfer to the mouse colon leads to intestinal fibrosis. Am J Physiol Gastrointest Liver Physiol. Jul;289(1):G116-128.

Burgess HA, Daugherty LE, Thatcher TH, Lakatos HF, Ray DM, Redonnet M, Phipps RP, Sime PJ. 2005. PPARgamma agonists inhibit TGF-beta induced pulmonary myofibroblast differentiation and collagen production: implications for therapy of lung fibrosis. Am J Physiol Lung Cell Mol Physiol. Jun;288(6):L1146-1153.

O’Reilly KM, Phipps RP, Thatcher TH, Graf BA, Van Kirk J, Sime PJ. 2005. Crystalline and amorphous silica differentially regulate the cyclooxygenase-prostaglandin pathway in pulmonary fibroblasts: implications for pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. Jun;288(6) L1010-1016.

Phipps, R.P., Beckett, W., Kaufman, J., Martey, C., Sime, P. J., and Thatcher, T. 2005. Anti-inflammatory therapies for lung injury. In: Lung injury: Mechanisms, pathophysiology and therapy. Notter, R., Finkelstein, J. and Holm, B. Eds., Taylor & Francis, Pp 573-616.

Baglole, C.J., Smith, T.J., Foster, D., Sime, P.J., Feldon, S., and Phipps, R.P. 2005. Functional assessment of fibroblast heterogeneity by the cell-surface glycoprotein Thy-1. In: Myofibroblasts, Editor: G. Gabbiani, C. Chaponnier, A. Desmouliere.

PubMed Publication List