Curriculum Vita

Bryan P. Hurley PhD
Assistant Professor of Pediatrics

GENERAL INFORMATION

Date Prepared: July 2008

Name: Bryan P. Hurley

Office Address:

Massachusetts General Hospital,
Building 114, Room 3700,
16th Street,
Charlestown, MA 02129

E-mail: bphurley@partners.org

Phone: 617-726-3101
Fax: 617-726-4172

ducation:

1994 - B.A. - College of the Holy Cross, Worcester MA (Biology)

2001 - Ph.D. - Tufts University Sackler School of Graduate Biomedical Sciences, Boston MA (Immunology)

Postdoctoral Training:

2001-2002 - Research Fellow, Combined Program of Pediatric Gastroenterology, Children’s Hospital, Boston MA

2002-2004 - Research Fellow, Department of Pediatrics / Mucosal Immunology Laboratory, Massachusetts General Hospital, Charlestown MA

Academic Appointments:

2004-2007 - Instructor, Department of Pediatrics, Harvard Medical School, Boston MA

2007- Current - Assistant Professor, Department of Pediatrics, Harvard Medical School, Boston, MA

Hospital or Affiliated Institution Appointments:

2001-2004 - Research Fellow, Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston MA

2004-2007 - Research Associate in Microbiology, Pediatric Service, Massachusetts General Hospital, Charlestown, MA

2007- Assistant Microbiologist, Pediatric Service, Massachusetts General Hospital, Charlestown MA

Administrative Responsibilities:

2008- Director of Laboratory Safety, Mucosal Immmunology Laboratory, Massachusetts General Hospital

Committee Assignments:

1999-2000 - Member of Graduate Student Admissions Committee for the Immunology Program at Tufts University Sackler School of Graduate Biomedical Sciences

2006 - Invited Peer Reviewer for the British Lung Foundation

2008 - Invited Peer Reviewer for Northern Ireland Chest Heart & Stroke Association

Memberships in Professional Societies:

2004- American Society of Microbiology (Member)

2004- Society for Mucosal Immunology (Member)

Editorial Boards:

2003- Ad. hoc. Reviewer:  Cellular Microbiology                       

2004- Ad. hoc. Reviewer:  Infection and Immunity           

Awards and Honors:

2003 - Ruth L. Kirschstein National Research Service Award

2008 - Research Scholar Development Award

2008 - Cystic Fibrosis Foundation Research Grant Recipient

Part II:  Research, Teaching, and Clinical Contributions

A. Narrative Report:

The innate immune system has received much investigative attention in recent years with the discovery of the true sophistication with which the non-adaptive early lines of defense can distinguish between a myriad of pathogenic signals. During my thesis studies in the Program of Immunology at Tufts University, I became fascinated with understanding innate inflammatory processes at mucosal surfaces. Upon completion of my thesis, I joined the Mucosal Immunology Laboratories at Massachusetts General Hospital to further pursue my interest in this important area of study, with a focus on lung disease.  Infiltration of the respiratory epithelia by neutrophils and their accumulation in the airspace is a common pathological feature observed during lung inflammatory diseases such as asthma, acute respiratory distress syndrome (ARDS), pneumonia, and cystic fibrosis.  This massive influx of neutrophils is generally believed to be responsible for the significant tissue damage associated with these severe lung conditions. To better understand how neutrophils are recruited during lung inflammation, I developed an in vitro assay to study neutrophil migration across lung epithelial cell barriers exposed to pathogenic bacteria.  Using this model, I have generated seminal data suggesting that the lung pathogenic bacteria stimulate neutrophil migration across lung epithelial monolayers by inducing epithelial production of an eicosanoid neutrophil chemo-attractant, hepoxilin A₃. The significance of this finding is far-reaching as this phenomenon represents a completely undiscovered innate immune pathway centered on a newly appreciated type of lipid chemo-attractant, which likely operates during many disease processes that are characterized by mucosal inflammation. Manipulating this innate immune pathway by interfering with hepoxilin A₃ production and subsequently reducing or preventing massive neutrophil influx holds significant promise for alleviating lung tissue damage occurring in patients with asthma, ARDS, pneumonia and cystic fibrosis.  My continued commitment to further elucidate the underlying mechanisms for this novel innate immune pathway will be complemented by the development of various disease models for the evaluation of the efficacy of pathway intervention therapeutics. 

In 2003, I received an Individual National Service Research Award (NRSA) and have published the discovery of hepoxilin A₃ as an innate mechanism occurring in the lung in the November 2004 issue of the Journal of Immunology. My mentor, Dr. Beth McCormick, and I received a Pilot and Feasibility Award from the Cystic Fibrosis Foundation in 2004, which I prepared based on data generated in my first couple years as a post-doctoral fellow. I am presently devoting the bulk of my time conducting research towards dissecting the molecular mechanisms of this novel innate immune pathway and have published recent findings in American Journal of Physiology Lung Cellular and Molecular Physiology and Clinical and Experimental Immunology. Recently, I received a commitment from the NIH in the form of a Research Scholar Development Award (K22), which provides funding for newly promoted faculty members. I have also received a two-year research grant from the Cystic Fibrosis Foundation with a competitive option for a third year.

As a member of the Mucosal Immunology Laboratory, my responsibilities include training summer students and teaching the Molecular Cell Biology Course offered by the department each summer.  I have mentored four summer students since I began in the Mucosal Immunology Laboratory and each student has presented their work at the departmental seminar series. All four students have entered either medical school or a biomedical science Ph.D. program. One student has earned co-authorship on my most recently published manuscript and another is a co-author on an abstract presented at an international meeting. I will continue to mentor students as well as assist junior research fellows entering the department, in addition to serving as an instructor for the various biomedical courses offered by the department.

B. Funding Information:

2003-2005 - National Institutes of Health, Ruth L. Kirshstein Individual NRSA (AI54054-02), Airway Inflammation: Bacterial / Epithelial Interactions, Principal Investigator: Bryan P. Hurley Ph.D.

2007-2006 - Cystic Fibrosis Foundation, Pilot and Feasibility Award, Identification of the Pseudomonas aeruginosa Factor Responsible for Inducing a Novel Inflammatory Pathway; Principal Investigator: Beth A. McCormick Ph.D.; Key Personnel: Bryan P. Hurley Ph.D.

2008 - Crohn’s and Colitis Foundation of America, Student Research Fellowship Award, The Role of Cystic Fibrosis Trans-membrane Receptor in Intestinal Inflammation; Principal Investigator: Daniel E. Schloss; Mentor: Bryan P. Hurley Ph.D.

2008-2010 - National Institute of Health, Research Scholar Development Award (1 K22 AI065425-01A2), Eicosanoid Production by Infected Lung Epithelial Cells; Principal Investigator: Bryan P. Hurley Ph.D.

2008-2010 - Cystic Fibrosis Foundation, Research Grant, Role of Eicosanoids and PMN Transmigration in Cystic Fibrosis; Principal Investigator: Bryan P. Hurley Ph.D.

C. Report of Current Research Activities:

1.     Project: Role of Eicosanoids and PMN Transmigration in Cystic Fibrosis
Role: Principal Investigator

2.     Project: Identification of Specific Phospholipase A₂ Enzymes Responsible for Bacterial Induced Hepoxilin A₃ Prodcution
Role: Principal Investigator

3.     Project: Determination of Pseudomonas aeruginosa Factor(s) Responsible for Stimulating Lung Epithelial Hepoxilin A₃ Release
Role: Principal Investigator.

4.     Project: Investigation of Differential Molecular Mechanisms Involved in Regulation of Eicosanoids in Infected Lung Epithelial Cells
Role: Principal Investigator.

5.     Project: Evaluation of the Efficacy of Hepoxilin A₃ Inhibition as a Treatment for Excessive Lung Inflammation in a Mouse Model of Infection
Role: Principal Investigator

6.      Project: The Role of Cystic Fibrosis Trans-membrane Receptor in Intestinal Inflammation
Role: Principal Investigator

D. Report of Teaching:

1. Local contributions:

Courses taught:

2000 - Immunology - Lecturer, Tufts Medical School

2003-2008 - Molecular Cell Biology - Instructor, Mass General Hospital

Each course is populated by mainly pre-medical students.  The Immunology course consisted of 15 course hours with 20 hours worth of preparation for a class size of 25 students.  The Molecular Cell Biology class is taught in the Mucosal Immunology Laboratory at Massachusetts General Hospital each summer is 20 course hours with 15 hours worth of preparation for a class size of 10 students.

Local Presentations:

2002 - “Shiga Toxin Translocation across Polarized Intestinal Epithelial Cells and the Role of Neutrophils in Toxin Movement”, Invited Seminar Speaker, Massachusetts General Hospital, Department of Pediatric Hematology / Oncology, Boston, MA

2003 - “Neutrophil Transmigration across Lung Epithelial Cells in Response to Infection with Pseudomonas aeruginosa”, Invited Seminar Speaker, Children’s Hospital, Department of Cell Biology, Boston, MA

2008 - “Involvement of Eicosanoids and Phospholipases in Mucosal Inflammation”, Invited Conference Speaker, Massachusetts General Hospital for Children, Pediatric Gastroenterology, Boston, MA

Advisory and supervisory responsibilities:

2002-current: I have mentored several summer students working within the Mucosal Immunology Laboratory at Massachusetts General Hospital.  My roles included the design of research projects for each student, training each student in laboratory techniques necessary for accomplishment of their individual projects, and assistance with analysis of their data and presentation of their results.  Currently I supervise a full time research technician and a postdoctoral fellow.

Advisees / Trainees:

Current:

Daniel Schloss, Summer Student
Waheed A. Pirzai    , Research Technician   

David L. Tamang Ph.D., Postdoctoral Fellow

Past:

2002 - Maytinee Lilaonitkul, Summer Student, Physician, London, U.K.

2003 - Natecia Williams, Summer Student, Pre-Doctoral Fellow, Department of Neurobiology, Washington University, St. Louis, MO

2004 - Patrick Murphy, Summer Student, Medical Student, Case Western Reserve University, Cleveland, OH

2007 - John Schomburg, Summer Student, Medical Student, Medical School at the University of Minnesota, Minneapolis, MN

2. Regional, national, or international contributions

a. Regional Invited presentations

2003 - “Bacterial Induced Neutrophil Transmigration across Lung Epithelial Monolayers”, Invited Plenary Session Speaker, Boston Bacterial Meeting, Boston, MA

2005 - “A Novel Mechanism Underlying Pseudomonas aeruginosa Induced Lung Inflammation”, Invited Seminar Speaker, New England Medical Center, Department of Geographic Medicine and Infectious Diseases, Boston, MA

2005 - “Molecular Mechanisms Underlying Pseudomonas aeruginosa Induced Neutrophil Migration across Lung Epithelial Cells, Invited Seminar Speaker, New England Medical Center, Pulmonary Critical Care and Sleep Division, Boston, MA

Part III: Bibliography:

Original Articles:

1. Fischer, C.P., Bode, B.P., Hurley, B.P. Souba W.W. Alterations in oxidative metabolism and glutamine transport support glucose production in the tumor-influenced hepatocyte.  J Surg Res.  1997; 69(2):379-84.

2. Hurley, B.P., Jacewicz, M., Thorpe, C.M., Lincicome, L.L., King, A.J., Keusch, G.T., Acheson, D.W.K. Shiga toxins 1 and 2 translocate differently across polarized intestinal epithelial cells.  Infect Immun.  1999; 67(12):6670-7.

3. Thorpe, C.M., Hurley, B.P., Lincicome, L.L., Jacewicz, M.S., Keusch, G.T., Acheson D.W.K..  Shiga toxins stimulate secretion of interleukin-8 from intestinal epithelial cells.  Infect Immun. 1999; 67(11):5985-93.

4. Thorpe, C.M., Flaumenhaft, R., Hurley, B., Jacewicz, M., Acheson, D.W.K., Keusch, G.T. Shiga toxins do not directly stimulate alpha-granule secretion or enhance aggregation of human platelets. Acta Haematol.  1999; 102(1):51-5.  

5. Hurley, B.P., Thorpe, C.M., Acheson, D.W.K.  Shiga toxin translocation across intestinal epithelial cells is enhanced by neutrophil transmigration.  Infect. Immun. 2001; 69(10):6148-55.

6.  Thorpe, C.M., Smith, W.E., Hurley, B.P., Acheson D.W.K. Shiga toxins induce, superinduce, and stabilize a variety of C-X-C chemokine mRNA in intestinal epithelial cells resulting in increased chemokine expression.  Infect. Immun.  2001; 69(10):6140-7.

7. Bode, B.P., Fuchs, B.C., Hurley, B.P., Conroy J.L., Suetterlin, J.E., Tanabe, K.K., Rhoads D.B., Abcouwer, S.F., Souba, W.W.  Molecular and functional analysis of glutamine uptake in human hepatoma and liver-derived cells.  Am J Physiol Gastrointest Liver Physiol.  2002; 283(5):G1062-73.

8. 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.

9. Spacek L.A., Hurley B.P., Acheson D.W., Granok A., Currie A., Doing K., Sears C.L. Shiga Toxin-Producing Escherichia coli as a Possible Etiological Agent of Chronic Diarrhea. Clin Infect Dis. 2004; 39(5):E46-8.

10. 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.

11. 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.

12.Köhler, H., Sakaguchi1, T., Hurley, B.P., Kase, B.A., Reinecker, H.C., McCormick, B.A. Salmonella regulates intercellular junction proteins and facilitates transepithelial neutrophil and bacterial passage.  Am J Physiol Gastro. and Liver Physiol.  2007; 293(1):G178-87.

13. 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.

14.  Mumy, K.L., Bien, J.D., Pazos, M.A., Gronert, K., Hurley, B.P., McCormick, B.A.  Distinct Isoforms of Phospholipase A2 mediate the ability of Salmonella enterica serotype Typhimurium and Shigella flexneri to induce the transepithelial migration of neutrophils.  Infect. Immun.  2008; 76(8):3614-27.

Reviews and Chapters:

1. Thorpe CM, Hurley BP, Acheson DWK.  Shiga Toxin Interactions with the Intestinal Epithelium.  In, Philpott, D.J., ed. Methods in Molecular Medicine. Totowa, NJ: Humana Press, 2002: 273:263-273

2. Hurley, BP and BA McCormick (2003) Translating tissue culture results into animal models: the case of Salmonella typhimurium. Trends in Microbiol. 11(12);562-9

3. Hurley, BP and BA McCormick (2004) Intestinal Epithelial Defense Systems Protect Against Bacterial Threats. Current Gastroenterology Reports.  6(5):355-61

4. Hurley, BP and BA McCormick (2008) Multiple Roles of Phospholipase A2 during Lung Infection and Inflammation.  Infect. Immun.  76(6):2259-2272

Thesis:

Hurley, B.P.  Shiga Toxin Translocation Across Polarized Intestinal Epithelial Cells and The Role of Neutrophils in Toxin Movement [Ph.D. Thesis], Boston, MA: Tufts University Sackler School of Biomedical Science, 2001 171 pp.

Published Abstracts:  (Within past two years / data not yet published)

1. Hurley, BP and B.A. McCormick.  The eicosanoid prostaglandin E2 is produced by lung epithelial cells infected with Pseudomonas aeruginosa by a mechanism distinct from Hepoxilin A3 production.  [Abstract] American Thoracic Society International Conference.  San Diego, CA.  May, 2006.

2. Hurley, BP and B.A. McCormick.  Role of Phospholipase A2 in Eicosanoid Production from Bacterial Infected Lung Epithelial Cells.  [Abstract] FASEB Summer Research Conference. “Phospholipases”.  Saxtons River, VT.  July, 2006.

3.  Hurley, B.P., A.L. Goodman, P. Murphy, S. Lory, B.A. McCormick.  2007.  The Two-Component Sensor Response Regulator RoxR / RoxS Plays a Role in Pseudomonas aeruginosa Adhesion to Airway Epithelial Cells.[Abstract] American Society for Microbiology.  Toronto, Ontario, Canada.  May, 2007.