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

Thatcher TH, Benson RP, Phipps RP, Sime PJ. High Dose but not Low Dose Mainstream Cigarette Smoke Suppresses Allergic Airway Inflammation by Inhibiting T Cell Function. Am J Physiol Lung Cell Mol Physiol. 2008 Jun 20. [Epub ahead of print]

Garcia-Bates TM, Lehmann GM, Simpson-Haidaris PJ, Bernstein SH, Sime PJ, Phipps RP Role of peroxisome proliferator-activated receptor gamma and its ligands in the treatment of hematological malignancies. PPAR Res. 2008;2008:834612. PMID: 18528522 [PubMed - in process]

Sime PJ.The antifibrogenic potential of PPARgamma ligands in pulmonary fibrosis. J Investig Med. 2008 Feb;56(2):534-538. Review.

Hart CM, Roman J, Reddy R, Sime PJ. PPARgamma: a novel molecular target in lung disease. J Investig Med. 2008 Feb;56(2):515-517.

Lakatos HF, Thatcher TH, Kottmann RM, Garcia TM, Phipps RP, Sime PJ. The Role of PPARs in Lung Fibrosis. PPAR Res. 2007:713-723.

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.

PubMed Publication List