Benjamin S. Bleier, M.D.

Harvard Medical School

Associate Professor of Otolaryngology

Massachusetts Eye and Ear

Investigator

Surgeon, Sinus Center

Co-Director, Center for Thyroid Eye Disease and Orbital Surgery

Director, Endoscopic Skull Base Surgery
 

Research Summary

Research Area Affiliations

Research Summary

Dr. Bleier’s research focuses on the role of sinonasal mucosal barrier function in the pathogenesis of chronic rhinosinusitis. Using a combination of immunohistochemical and air-liquid interface primary epithelial culture techniques, his laboratory is working to determine how transmembrane epithelial proteins, such as the ATP-binding cassette(ABC) transporter P-glycoprotein, functions to promote the elaboration of Th1 and Th2 skewed cytokines in the setting of chronic inflammatory disease states (Figure).

An additional synergistic interest is studying mucosal permeability and epithelial responses to a variety of topical therapeutics and drug eluting polymers. Using both in vitro and animal models, Dr. Bleier is working to develop methods to bypass the blood-brain barrier using advanced endoscopic surgical techniques. He also studies the ability to couple these procedures with biocompatible materials to enhance the treatment of neurodegenerative disorders and local sinonasal disease.

Current Projects

Endoscopic Orbital Surgery
Along with collaborators from the division of Ophthalmic Plastic Surgery, Dr. Bleier, Co-Director of the Center for Thyroid Eye Disease and Orbital Surgery, is developing an array of minimally invasive surgical approaches to the orbit including new methods for orbital decompression and dacryocystorhinostomy. His team has pioneered an endoscopic method to remove orbital tumors entirely through the nose while avoiding any external incisions.

Trans-Nasal Drug Delivery to the Central Nervous System
The Bleier Lab has developed the first and only method to permanently bypass the blood-brain barrier using nasal mucosal grafts. Dr. Bleier and his collaborators have used this method to deliver high molecular weight proteins and nucleic acids to the brain which would otherwise be restricted by the blood-brain barrier. This approach has been recognized by the Michael J. Fox Foundation, Boston Magazine, Harvard Medicine Magazine, and Scientist Magazine. Current projects are directed at using this delivery pathway to develop new treatments for neurodegenerative disorders including Alzheimer’s and Parkinson’s disease.

Proteomic Approach to the Diagnosis and Treatment of Chronic Rhinosinusitis
The Bleier Lab has discovered the presence of P-glycoprotein (P-gp) upregulation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). This overexpression directly leads to the selective epithelial hypersecretion of Th2 polarizing cytokines which are characteristic of CRSwNP. Dr. Bleier recently completed a double-blind, placebo-controlled, randomized clinical trial demonstrating that inhibition of P-gp is effective in controlling both subjective and objective symptoms of nasal polyps. His lab has further shown that both P-gp and other proteins are released into nasal mucus via exosomes. These mucus derived exosomes or “rhinosomes” be non-invasively detected to generate a novel quantitative biosignature of CRS using a proteomic array. This biosignature can then be used to classify patients by disease endotype and guide therapy by predicting the specific inflammatory pathways which may be up or downregulated.


Select Publications

Antibiotic eluting chitosan glycerophosphate implant in the setting of acute bacterial sinusitis: A rabbit model. Bleier BS, Kofonow JM, Hashmi N, Chennupati SK, Cohen NA. Am J Rhinol Allergy. 2010 Mar–Apr. 24(2):129–32

Primary human sinonasal epithelial cell culture model for topical drug delivery in patients with chronic rhinosinusitis with nasal polyposis
. Bleier BS, Mulligan RM, Schlosser RJ. J Pharm Pharmacol. 2012 Mar. 64(3):449–56.

P-glycoprotein functions as an immunomodulator in healthy human primary nasal epithelial cells. Bleier BS, Nocera AL, Iqbal H, Hoang JD, Feldman RE, Han X. Int Forum Allergy Rhinol. 2013 Mar 20.

Permeabilization of the blood-brain barrier via mucosal engrafting: Implications for drug delivery to the brain. Bleier BS, Kohman RE, Feldman RE, Ramanlal S, Han X. PLoS One. 2013 Apr 24. 8(4):e61694.

P-glycoprotein is a marker of tissue eosinophilia and radiographic inflammation in chronic rhinosinusitis without nasal polyps. Feldman RE, Lam AC, Sadow PM, Bleier BS. Int Forum Allergy Rhinol. 2013 May 15.

View a complete list of publications on pubmed.gov »

Textbooks

Biosketch

Education

2000: BA Biology, University of Pennsylvania
2004: MD, University of Pennsylvania

Postgraduate Training

2005: Internship, General Surgery, University of Pennsylvania
2009: Residency, Otorhinolaryngology—Head and Neck Surgery, University of Pennsylvania
2010: Fellowship, Rhinology and Endoscopic Skull Base Surgery, Medical University of South Carolina

Professional Memberships

2005–present: American Academy of Otolaryngology—Head and Neck Surgery (AAO-HNS)
2007–present: American Rhinologic Society (ARS)
2011–present: Member, Rhinology and Allergy Education Committee, AAO-HNS
2013–present: Member, Home Study Course Committee, AAO-HNS
2014–present: Chair, Research and Grants Committee, ARS
2014–present: Massachusetts Society of Otolaryngology-Head and Neck Surgery, Inc.
2014–present: Member, Learning Management Advisory Committee, AAO-HNS
2015–present: Triological Society

Awards and Honors

2008: First Place in Basic Science, Philadelphia College of Physicians Resident Research Competition, Animal Model of Laser Welded Esophageal Repair
2013: Runner-up in Basic Science, American Rhinologic Society Spring Meeting
2014: ARS Junior Member Research Travel Award, 25th Congress of European Rhinologic Society, Amsterdam, The Netherlands
2014: Norman Knight Leadership Development Award, Mass. Eye and Ear
2014: Best Video at 1st Annual FESStival, American Academy of Otolaryngology—Head and Neck Surgery Foundation
2015: Honors Award, American Academy of Otolaryngology—Head and Neck Surgery Foundation
2015: Best Video at 2nd Annual FESStival, American Rhinologic Society
2015: Finalist 2nd Annual FESStival, American Rhinologic Society
2016: Best Basic Science Presentation, American Rhinologic Society
2016: Presidential Citation, American Rhinologic Society
2016: Distinguished Service Award, American Academy of Otolaryngology—Head and Neck Surgery Foundation
2017: 2nd Place in Poster Competition, American Rhinologic Society

Teaching

2010–present: Mass. Eye and Ear Sinus Dissection Course, Otolaryngology Residents
2011: Introduction to Neuroengineering, Undergraduate/Graduate Students
2013–present: Boston Sinus Dissection Course, Otolaryngology Residents

Editorial Roles

International Forum of Allergy and Rhinology (Associate Editor)
World Journal of Otorhinolaryngology—Head and Neck Surgery (Editorial Board)
American Journal of Rhinology and Allergy (Former Associate Editor)
Laryngoscope (Ad hoc Reviewer)
Journal of Pharmacy and Pharmacology (Ad hoc Reviewer)
Otolaryngology—Head and Neck Surgery (Ad hoc Reviewer)
Skull Base (Ad hoc Reviewer)