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Research at Mass General
The Hurley Laboratory’s research objective is to better understand how injury, infection, and genetic predisposition can drive mucosal inflammation that leads to tissue damage associated with both acute and chronic mucosal diseases such as pneumonia, cystic fibrosis and inflammatory bowel disease. Specifically, our research explores how bacterial pathogens and other noxious agents impact the mucosal barrier’s integrity at the respiratory and digestive surface and provoke inflammatory responses. We are actively exploring cellular and molecular mechanisms involved in orchestrating neutrophil trans-epithelial migration (i.e. how neutrophils breach mucosal epithelial barriers).
We have discovered an inducible, tightly regulated process involving the release of lipid mediators, known as eicosanoids that function as neutrophil chemo-attractants, directing neutrophils to breach intact epithelial barriers. A more thorough understanding of the mucosal barrier, its vulnerabilities and how inflammation can disrupt its integrity will inform the development of new therapies for managing excessive inflammation in the face of a diverse array of external threats and internal factors.
Bryan P. Hurley, PhDDirector, MGHfC Digestive Disease Summer Research ProgramAssistant Professor of Pediatrics, Harvard Medical School
Lael M. Yonker, MDCo-Director, MGH Cystic Fibrosis Center Co-Director, MGH Cystic Fibrosis Therapeutic Development Center Co-Director, Pulmonary Genetics Clinic Instructor, Harvard Medical SchoolFind a Doctor Profile
Eliana Drenkard, PhDInstructor, Harvard Medical School
Bernard B. Lanter, PhDPostdoctoral Fellow
Alex D. EatonResearch Technician II
Rhianna M. HibblerResearch Technician II
Investigation of the role of epithelial-derived hepoxilin A3 and neutrophil-derived leukotriene B4 in orchestrating bacterial induced neutrophil trans-epithelial migration.
Characterization of cellular and molecular mechanisms of neutrophilic mucosal breach in healthy and diseased states through the development of primary human ex vivo co-culture models paired with live micro-optical coherence tomography imaging.
Replication and distribution of the Pseudomonas aeruginosa, strain PA14, non-redundant transposon insertion mutant library. More Info
Consequences of extra-esophageal reflux on airway infection and inflammation.
Development of an in vitro experimental platform using polarized human intestinal epithelial monolayers to differentiate between hazardous and non-hazardous proteins.
Yonker LM, Pazos MA, Lanter BB, Mou H, Chu KK, Eaton AD, Bonventre JV, Tearney GJ, Rajagopal J, Hurley BP. Neutrophil-derived cytosolic PLA2α contributes to bacterial-induced neutrophil trans-epithelial migration. J Immunol. 2017; 199(8):2873-2884. PMC5636676.
Yonker LM, Mou H, Chu KK, Pazos MA, Leung H, Cui D, Ryu J, Hibbler RM, Eaton AD, Ford TN, Falck JR, Kinane TB, Tearney GJ, Rajagopal J, Hurley BP. Development of a Primary Human Co-Culture Model of Inflamed Airway Mucosa. Sci Rep. 2017; 7(1):8182. PMC5557980.
Pazos MA, Lanter BB, Yonker LM, Eaton AD, Pirzai W, Gronert K, Bonventre JV, Hurley BP. Pseudomonas aeruginosa ExoU augments neutrophil transepithelial migration. PLoS Pathog. 2017; 13(8): e1006548. PMC5557605.
Chu KK, Kusek ME, Liu L, Som A, Yonker LM, Leung H, Cui D, Ryu J, Eaton AE, Tearney GJ, Hurley BP. Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography. Sci Rep. 2017; 8, 45789. PMC5377939.
Eaton AD, Zimmermann C, Delaney B, Hurley BP. Primary human polarized small intestinal epithelial barriers respond differently to a hazardous and an innocuous protein. Food Chem Toxicol. 2017 106(Pt A):70-77. PMID: 28533127.
Hurley BP, Eaton AD, Zimmermann C, Delaney B. Polarized monolayer cultures of human intestinal epithelial cell lines exposed to intractable proteins - In vitro hazard identification studies. Food Chem Toxicol. 2016; 98(Pt B):262-268. PMID: 27832974.
Chen K, Shanmugam NK, Pazos MA, Hurley BP, Cherayil B.J. Commensal Bacteria-Induced Inflammasome Activation in Mouse and Human Macrophages Is Dependent on Potassium Efflux but Does Not Require Phagocytosis or Bacterial Viability. PLoS One. 2016; 11(8): e0160937. PMC4978417.
Johnston N, Ondrey F, Rosen R, Hurley BP, Gould J, Allen J, DelGaudio J, Altman KW. Airway reflux. Ann N Y Acad Sci. 2016; 1381(1):5-13. PMID: 27310222.
Hurley BP, Pirzai W, Eaton AD, Harper M, Roper J, Zimmermann C, Ladics GS, Layton RJ, Delaney B. An experimental platform using human intestinal epithelial cell lines to differentiate between hazardous and non-hazardous proteins. Food Chem Toxicol. 2016 Jun;92:75-87. PMID: 27060235.
Yonker LM, Cigana C, Hurley BP, Bragonzi A. Host-pathogen interplay in the respiratory environment of cystic fibrosis. J Cyst Fibros. 2015:14(4):431-9. PMC4485938.
Pazos MA, Pirzai W, Yonker LM, Morisseau C, Gronert K, Hurley BP. Distinct cellular sources of hepoxilin A3 and leukotriene B4 are used to coordinate bacterial-induced neutrophil transepithelial migration. J Immunol. 2015 Feb 1; 194(3):1304-15. PMC4297725.
Hurley BP (2014)Phospholipases in Health and Disease. Tappia PS, Dhalla NS, editors. New York, NY: Springer. Chapter 8, Phospholipase A2 Activity Exhibited by a Bacterial Virulence Protein that Enters and Operates within a Variety of Host Cells; p.135-146. 410p.
Kubala SA, Patil SU, Shreffler WG, Hurley BP. Pathogen induced chemo-attractant hepoxilin A3 drives neutrophils, but not eosinophils across epithelial barriers. Prostaglandins Other Lipid Mediat. 2014 Jan; 108:1-8. PMC4004677.
Kusek ME, Pazos MA, Pirzai W, Hurley BP. In Vitro Co-Culture Assay to Assess Pathogen Induced Neutrophil Trans-Epithelial Migration. J. Vis. Exp. 2014; Jan 6;(83):e50823. PMC4063550.
Bhowmick R, Tin Maung NH, Hurley BP, Ghanem EB, Gronert K, McCormick BA, Leong JM. Systemic disease during Streptococcus pneumoniae acute lung infection requires 12-lipoxygenase-dependent inflammation. J Immunol. 2013 Nov 15;191(10):5115-23. PMC3836588.
Trebicka E, Jacob S, Pirzai W, Hurley BP, Cherayil BJ. Role of anti-lipopolysaccharide antibodies in serum bactericidal activity against Salmonella enterica serovar Typhimurium in healthy adults and children in the United States. Clin Vaccine Immunol. 2013 Oct;20(10):1491-8. PMC3807195.
Tamang DL, Pirzai W, Priebe GP, Traficante DC, Pier GB, Falck JR, Morisseau C, Hammock BD, McCormick BA, Gronert K, Hurley BP. Hepoxilin A3 Facilitates Neutrophilic Breach of Lipoxygenase-Expressing Airway Epithelial Barriers. J Immunol. 2012; 189(10):4960-9. PMC3490410.
Hurley BP, Pirzai W., Mumy KL, Gronert K, McCormick BA. Selective Eicosanoid Generating Capacity of Cytoplasmic Phospholipase A2 in Pseudomonas aeruginosa Infected Epithelial Cells. Am J Physiol Lung Cell Mol Physiol. 2011; 300(2):L286-94. PMC3043809.
Hurley BP, Goodman AL, Murphy P, Lory S, McCormick BA. The Two-Component Sensor Response Regulator RoxR / RoxS Plays a Role in Pseudomonas aeruginosa Interactions with Airway Epithelial Cells. Microbes & Infection. 2010; 12(3):190-8. PMC2826603.
Contact the Hurley Laboratory
Bryan P. Hurley, PhD Director, MGHfC Digestive Disease Summer Research Program Assistant Professor of Pediatrics, Harvard Medical School The Mucosal Immunology & Biology Research Center
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