Research

Bryan P. Hurley PhD
Assistant Professor of Pediatrics

Phone: 617-726-3101
Fax: 617-726-4172
Email: bphurley@partners.org

Curriculum Vita

Fellows: David L. Tamang Ph.D.

The major focus of our lab is to explore the molecular mechanisms that underlie neutrophil migration across the airway epithelium. The epithelial cell layer of the mucosal surface that lines the airway of the respiratory system represents a major barrier to the invasion of pathogens or to the internalization of noxious substances. In addition to functioning as a physical barrier, the epithelial cell layer is capable of sensing the presence of insult or infection and responding by directly engaging components of the immune system charged with confronting the threat. One important consequence of epithelial cell sensing is the recruitment of neutrophils from the bloodstream to the mucosal surface where these cells can migrate across the epithelial lining into the airspace. Neutrophil trans-epithelial migration is a major pathological hallmark of numerous airway inflammatory diseases of both infectious and non-infectious origin, including pneumonia, cystic fibrosis, chronic obstructive pulmonary disease (COPD), and asthma. Neutrophils are recruited to the airspace by inflammatory signals for the purposes of host defense, however these potentially detrimental immune cells can accumulate and become destructive resulting in lung tissue damage leading to severe pathological consequences. 

We have previously reported that lung pathogens, including Pseudomonas aeruginosa, stimulate neutrophil migration across lung epithelial monolayers in a manner independent of the well-studied protein neutrophil chemokine, IL-8. Our studies suggest lung epithelial cells produce the eicosanoid, hepoxilin A₃, in a protein kinase C-dependant manner. Production of hepoxilin A₃ occurs in response to infection with Pseudomonas aeruginosa, whereby secreted hepoxilin A₃ serves as a chemo-attractant to direct neutrophils across lung epithelial barriers. In addition, we have uncovered an important role for phospholipase A₂ in bacterial induced neutrophil migration across lung epithelial cells. Phospholipase A₂ is the enzyme mainly responsible for the conversion of membrane phospholipids into arachidonic acid, which serves as the precursor for eicosinoids such as hepoxilin A₃.  Our group is also investigating whether infection with Pseudomonas aeruginosa induces the production of other eicosinoids such as prostaglandins and how the epithelial cell is able to partition arachidonic acid into different eicosinoids upon encountering infectious stimuli. Another important component of our studies includes executing strategies to identify the Pseudomonas aeruginosa factor(s) responsible for stimulating the signaling pathway leading to the production of hepoxilin A₃. Evaluating the relevance of the process in animal models of lung inflammation and assessing the prevalence of this inflammatory pathway in primary human lung tissue are important objectives being pursued by our group. The ultimate goal of our research is to design targeted therapies capable of reducing neutrophil trans-epithelial migration in vivo with the aim of alleviating the pathological consequences associated with excessive neutrophil recruitment, a phenomenon associated with multiple lung inflammatory diseases.

Selected Publications 

1. Hurley, B.P. and B.A. McCormick.  Intestinal Epithelial Defense Systems Protect Against Bacterial Threats. Current Gastroenterology Reports.  2004; 6(5):355-61
2. Mrsny, R.J., Gewirtz, A.T. , Siccardi,,D., Savidge, T.C.,  Hurley, B.P.,  Madara, JL, McCormick, B.A. Identification of hepoxilin A3 in inflammatory events: A required role in neutrophil migration across the intestinal epithelia. Proc. Natl. Acad. Sci. USA 2004; 101: 7421-7426.
3. Hurley, B.P., Siccardi, D., Mrsny, R.J., McComick, B.A.  PMN transepithelial migration induced by Pseudomonas aeruginosa requires the eicosinoid hepoxilin A3. J Immunol. 2004; 173(9):5712-20.
4. Hurley, B.P., Williams, N.L., McCormick, B.A.  Involvement of Phospholipase A2 in Pseudomonas aeruginosa Mediated PMN Trans-epithelial Migration.  Am J Physiol Lung Cell Mol Physiol.  2006; 290(4):L703-9.
5. Hurley, B.P., Sin, A., McCormick, B.A.  Adhesion Molecules Involved in Hepoxilin A3 Mediated PMN Trans-epithelial Migration.  Clin. and Exp. Immuno.  2008; 151(2):297-305.
6. Hurley, B.P. and B.A. McCormick.  Multiple Roles of Phospholipase A2 during Lung Infection and Inflammation.  Infect. Immun.  2008; 76(6):2259-2272

Current Trainees

David L. Tamang Ph.D. - Postdoctoral Fellow
Waheed A. Pirzai - Research Technician   
Daniel E. Schloss - Summer Student