About My Research
Dr. Holbrook’s research looks at ways to understand the ability of the olfactory epithelium to regenerate after injury. His long-term goal is to integrate what is learned in the laboratory with his clinical understanding of olfactory loss to either prevent further progression or reverse the process of smell loss in humans. Previous research projects supported the finding of odorant evoked neuronal activity in the enhancement of survival and axonal targeting of receptor neurons after olfactory epithelial lesions in mice. This suggests a possible role for odorant therapy in the treatment of human olfactory disorders. A clinical study is being developed to test this therapy.
Further research has focused on the characterization of the olfactory mucosa in humans and a comparison with staining and molecular expression patterns identified in rodents. A description of reproducible staining patterns in various regenerative states can help propose mechanisms of pathology in human olfactory disorders that show comparable patterns in biopsy specimens. Dr. Holbrook has demonstrated that mouse and human epithelium are remarkably similar, and the human mucosa appears to retain regenerative capacity even in extreme ages. The olfactory area seems to decrease with age, but to a lesser degree than we anticipated.
Given the findings in human autopsy material, potentially the problems of smell loss related to aging may be a function of abnormalities with the bulb or brain instead of the epithelium. Abnormalities of central areas may also occur with other forms of human olfactory loss as a primary source or as a secondary outcome to long-term denervation. A permanent alteration of central areas may make efforts at repairing epithelial disorders ineffective for treating smell loss. To study the effects of long-term olfactory neuronal loss on both the epithelium and central areas we have developed a novel mouse model of an inducible and reversible lesion. The findings mirror some examples we see in human olfactory tissue.
In addition to research on the sense of smell, multiple clinical projects relating to outcomes in the treatment of sinus disease and the mechanisms of chronic sinusitis are currently ongoing. Many of these projects are in conjunction with other faculty at Mass. Eye and Ear, as well as specialists from Mass General in the allergy and neurosurgery fields.
Education
BS, Biology, Cornell University
MD/MS, SUNY Health Science Center
Postgraduate Training
Internship, General Surgery, SUNY Health Science Center
Residency, Otolaryngology–Head and Neck Surgery, Medical College of Virginia
Fellowship, Rhinology, University of Nebraska Medical Center
Professional Societies
American Academy of Otolaryngology–Head and Neck Surgery
American Rhinologic Society
Association for Chemoreception Sciences
Massachusetts Society of Otolaryngology–Head and Neck Surgery
Society of University Otolaryngologists–Head and Neck Surgeons
Massachusetts Medical Society
Society of Neuroscience
Triological Society
Honors (select)
American Heart Association Medical Student Research Fellowship
American Federation for Clinical Research Award
Medical Student Research Program Certificate
NIH, NRSA Postdoctoral Research Fellow
Clinical Travel Fellowship, Association for Chemoreception Sciences
Travel Award, Association for Research in Otolaryngology
Resident Presentation Award, Annual Meeting of the Virginia Society of Otolaryngology–Head and Neck Surgery
Outstanding Achievement in Research, Department of Otolaryngology, Medical College of Virginia
Clinical Travel Fellowship, Association for Chemoreception Sciences
Triological Society Fellow
- Endoscopic endonasal approach for olfactory groove meningioma resection: Strategies and outcomes in a retrospective case series. J Clin Neurosci. 2024 Apr; 122:93-102.
- Five-year EuroQol 5-Dimension Outcomes After Endoscopic Sinus Surgery. Laryngoscope. 2023 Dec 21.
- Trends of Odontogenic Sinusitis Incidence During the COVID-19 Pandemic. Laryngoscope. 2024 Apr; 134(4):1597-1602.
- What Is Different in COVID-19-Associated Olfactory Loss from Classical Postinfectious Olfactory Impairment? ORL J Otorhinolaryngol Relat Spec. 2023; 85(5):245-247.
- Developing a core outcome set for clinical trials in olfactory disorders: a COMET initiative. Rhinology. 2023 Aug 01; 61(4):312-319.
- Position paper on olfactory dysfunction: 2023. Rhinology. 2023 Jul 16.
- Olfactory Nomenclature: An Orchestrated Effort to Clarify Terms and Definitions of Dysosmia, Anosmia, Hyposmia, Normosmia, Hyperosmia, Olfactory Intolerance, Parosmia, and Phantosmia/Olfactory Hallucination. ORL J Otorhinolaryngol Relat Spec. 2023; 85(6):312-320.
- Molecular Evidence for Olfactory Neuroblastoma as a Tumor of Malignant Globose Basal Cells. Mod Pathol. 2023 05; 36(5):100122.
- Techniques in Staining of Rodent and Human Olfactory Tissue. Methods Mol Biol. 2023; 2710:195-207.
- Safety, tolerability, and effectiveness of anticoagulation and antiplatelet therapy in hereditary hemorrhagic telangiectasia. J Thromb Haemost. 2023 01; 21(1):26-36.
- Posterior Ischemic Optic Neuropathy in the Setting of Cocaine-Induced Orbital and Sinonasal Inflammation. Ophthalmic Plast Reconstr Surg. 2022 Sep-Oct 01; 38(5):e141-e144.
- Defining the Health Utility Value of Medical Management of Chronic Rhinosinusitis: A Prospective Pilot Study. OTO Open. 2022 Apr-Jun; 6(2):2473974X221092381.
- Integrated age-related immunohistological changes occur in human olfactory epithelium and olfactory bulb. J Comp Neurol. 2022 08; 530(12):2154-2175.
- Rapid fluorescent vital imaging of olfactory epithelium. iScience. 2022 May 20; 25(5):104222.
- International consensus statement on allergy and rhinology: Olfaction. Int Forum Allergy Rhinol. 2022 04; 12(4):327-680.
- A Rare Complication of Chronic Otitis Media: Central Skull Base Osteomyelitis Managed With Combined Endoscopic Transmastoid and Transsphenoidal Debridement. Otol Neurotol. 2022 03 01; 43(3):e344-e347.
- Therapies for Olfactory Dysfunction - an Update. Curr Allergy Asthma Rep. 2022 03; 22(3):21-28.
- Private payer-negotiated prices for FDA-approved biologic treatments for allergic diseases. Int Forum Allergy Rhinol. 2022 05; 12(5):798-801.
- Post-viral effects of COVID-19 in the olfactory system and their implications. Lancet Neurol. 2021 09; 20(9):753-761.
- Observed progression from melanosis with melanocyte hyperplasia to sinonasal melanoma with distant metastasis and a unique genetic rearrangement. J Cutan Pathol. 2021 Jul; 48(7):948-953.
- Systemic corticosteroids in coronavirus disease 2019 (COVID-19)-related smell dysfunction: an international view. Int Forum Allergy Rhinol. 2021 07; 11(7):1041-1046.
- International consensus statement on allergy and rhinology: rhinosinusitis 2021. Int Forum Allergy Rhinol. 2021 03; 11(3):213-739.
- Clinical Olfactory Working Group consensus statement on the treatment of postinfectious olfactory dysfunction. J Allergy Clin Immunol. 2021 05; 147(5):1704-1719.
- Prophylactic antibiotics after endoscopic sinus surgery for chronic rhinosinusitis: a randomized, double-blind, placebo-controlled noninferiority clinical trial. Int Forum Allergy Rhinol. 2021 07; 11(7):1047-1055.
- Innate immune signaling in the olfactory epithelium reduces odorant receptor levels: modeling transient smell loss in COVID-19 patients. medRxiv. 2020 Jun 16.
- Endoscopic management of lateral sphenoid cerebrospinal fluid leaks: Identifying a radiographic parameter for surgical planning. Laryngoscope Investig Otolaryngol. 2020 Jun; 5(3):375-380.
- A primer on viral-associated olfactory loss in the era of COVID-19. Int Forum Allergy Rhinol. 2020 Jul; 10(7):814-820.
- Airborne Aerosol Generation During Endonasal Procedures in the Era of COVID-19: Risks and Recommendations. Otolaryngol Head Neck Surg. 2020 09; 163(3):465-470.
- Endonasal instrumentation and aerosolization risk in the era of COVID-19: simulation, literature review, and proposed mitigation strategies. Int Forum Allergy Rhinol. 2020 Jul; 10(7):798-805.
- Smell and taste dysfunction in patients with COVID-19. Lancet Infect Dis. 2020 09; 20(9):1015-1016.
- Clinical Practice Guideline: Nosebleed (Epistaxis) Executive Summary. Otolaryngol Head Neck Surg. 2020 01; 162(1):8-25.
- Clinical Practice Guideline: Nosebleed (Epistaxis). Otolaryngol Head Neck Surg. 2020 01; 162(1_suppl):S1-S38.
- Human Papillomavirus Related Multiphenotypic Sinonasal Carcinoma: Report of a Case with Early and Progressive Metastatic Disease. J Neurol Surg Rep. 2019 Oct; 80(4):e41-e43.
- Cranial Nerve Stimulation for Olfaction (Cranial Nerve 1). Otolaryngol Clin North Am. 2020 Feb; 53(1):73-85.
- Activating a Reserve Neural Stem Cell Population In Vitro Enables Engraftment and Multipotency after Transplantation. Stem Cell Reports. 2019 04 09; 12(4):680-695.
- Improvement in nasal obstruction and quality of life after septorhinoplasty and turbinate surgery. Laryngoscope. 2019 07; 129(7):1554-1560.
- Does bilateral inferior turbinate reduction affect long-term quality-of-life outcomes in patients undergoing endoscopic sinus surgery? Int Forum Allergy Rhinol. 2019 06; 9(6):601-606.
- The intraoperative accuracy of maxillary balloon dilation: a blinded trial. Int Forum Allergy Rhinol. 2019 05; 9(5):452-457.
- Induction of smell through transethmoid electrical stimulation of the olfactory bulb. Int Forum Allergy Rhinol. 2019 02; 9(2):158-164.
- SNOT-22 score patterns strongly negatively predict chronic rhinosinusitis in patients with headache. Int Forum Allergy Rhinol. 2019 01; 9(1):9-15.
- The Neuroregenerative Capacity of Olfactory Stem Cells Is Not Limitless: Implications for Aging. J Neurosci. 2018 08 01; 38(31):6806-6824.
- Meningoencephalocele and Cerebrospinal Fluid Leak Complicating Orbital Decompression. Ophthalmic Plast Reconstr Surg. 2018 May-Jun; 34(3):e79-e81.
- Characterization and Correction of Olfactory Deficits in Kidney Disease. J Am Soc Nephrol. 2017 Nov; 28(11):3395-3403.
- Does the Timing of Middle Turbinate Resection Influence Quality-of-Life Outcomes for Patients with Chronic Rhinosinusitis? Otolaryngol Head Neck Surg. 2017 11; 157(5):874-879.
- Position paper on olfactory dysfunction. Rhinol Suppl. 2017 03; 54(26):1-30.
- Double-blind placebo-controlled randomized clinical trial of verapamil for chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2017 07; 140(1):271-273.
- Phantosmia and Dysgeusia following Endoscopic Transcribriform Approaches to Olfactory Groove Meningiomas. J Neurol Surg B Skull Base. 2017 Jun; 78(3):245-250.
- Factors influencing the need for endoscopic sinus surgery in adult patients with cystic fibrosis. Am J Rhinol Allergy. 2017 Jan 01; 31(1):44-47.
- Aseptic Meningitis with Craniopharyngioma Resection: Consideration after Endoscopic Surgery. J Neurol Surg Rep. 2016 Oct; 77(4):e151-e155.
- Stem and progenitor cells of the mammalian olfactory epithelium: Taking poietic license. J Comp Neurol. 2017 Mar 01; 525(4):1034-1054.
- Impact of endoscopic dacryocystorhinostomy on sinonasal quality of life. Am J Rhinol Allergy. 2016 Sep; 30(5):189-91.
- General antibiotic exposure is associated with increased risk of developing chronic rhinosinusitis. Laryngoscope. 2017 02; 127(2):296-302.
- An Algorithm for Surgical Approach to the Anterior Skull Base. J Neurol Surg B Skull Base. 2016 Aug; 77(4):364-70.
- Office-based olfactory mucosa biopsies. Int Forum Allergy Rhinol. 2016 06; 6(6):646-53.
- Position paper on olfactory dysfunction. Rhinology. 2016 01 31; 56(1):1-30.
- Nasal mucosal melanosis may act as a harbinger of melanoma: A case report. Allergy Rhinol (Providence). 2016 Jan 01; 7(3):164-167.
- Skull base erosion and associated complications in sphenoid sinus fungal balls. Allergy Rhinol (Providence). 2016 Jan 01; 7(4):227-232.
- Surgical risk factors for recurrence of inverted papilloma. Laryngoscope. 2016 Apr; 126(4):796-801.
- The impact of surgical trainee participation on sinus surgery outcomes. Laryngoscope. 2016 Feb; 126(2):316-21.
- Plasmacytoma of the Clivus Presenting as Bilateral Sixth Nerve Palsy. J Neurol Surg Rep. 2015 Jul; 76(1):e156-9.
- Invasive fungal disease of the sinus and orbit: a comparison between mucormycosis and Aspergillus. Br J Ophthalmol. 2016 Feb; 100(2):184-8.
- Immediate and Delayed Complications Following Endoscopic Skull Base Surgery. J Neurol Surg B Skull Base. 2015 Sep; 76(5):390-6.
- Volumetric analysis of chronic maxillary atelectasis. Am J Rhinol Allergy. 2015 May-Jun; 29(3):166-9.
- Profibrotic transforming growth factor beta 1 and activin A are increased in nasal polyp tissue and induced in nasal polyp epithelium by cigarette smoke and Toll-like receptor 3 ligation. Int Forum Allergy Rhinol. 2015 Jul; 5(7):573-82.
- EQ-5D-derived health utility values in patients undergoing surgery for chronic rhinosinusitis. Laryngoscope. 2015 May; 125(5):1056-61.
- The regeneration of P2 olfactory sensory neurons is selectively impaired following methyl bromide lesion. Chem Senses. 2014 Sep; 39(7):601-16.
- The EQ-5D: a new tool for studying clinical outcomes in chronic rhinosinusitis. Laryngoscope. 2015 Jan; 125(1):7-15.
- Treatment outcomes and prognostic factors, including human papillomavirus, for sinonasal undifferentiated carcinoma: a retrospective review. Head Neck. 2015 Mar; 37(3):366-74.
- Long-Term Outcomes in Sinus Surgery: A New Tool for Measuring Health-Related Quality of Life. Otolaryngol Head Neck Surg. 2014 07; 151(1):164-70.
- A new model for collection of clinical outcomes data in patients with chronic rhinosinusitis. Int Forum Allergy Rhinol. 2014 May; 4(5):411-5.
- The perforation technique: a modification to the frontal sinus osteoplastic flap. Laryngoscope. 2014 Jun; 124(6):1314-7.
- Proteoglycan abnormalities in olfactory epithelium tissue from subjects diagnosed with schizophrenia. Schizophr Res. 2013 Nov; 150(2-3):366-72.
- Outcomes analysis in epistaxis management: development of a therapeutic algorithm. Otolaryngol Head Neck Surg. 2013 Sep; 149(3):390-8.
- Nasal hamartoma associated with duplicated pituitary. J Comput Assist Tomogr. 2013 May-Jun; 37(3):369-70.
- Diagnostic characteristics of sinonasal organizing hematomas: avoiding misdiagnosis. Int Forum Allergy Rhinol. 2013 Jul; 3(7):598-602.
- Skull base anatomy and CSF rhinorrhea. Adv Otorhinolaryngol. 2013; 74:1-11.
- Management of severe epistaxis after Young's procedure: a case report. Int Forum Allergy Rhinol. 2013 Apr; 3(4):334-7.
- Distorted olfactory perception: a systematic review. Acta Otolaryngol. 2012 Jun; 132 Suppl 1:S27-31.
- Syndrome of inappropriate antidiuretic hormone secretion in patients with olfactory neuroblastoma. Otolaryngol Head Neck Surg. 2012 Jul; 147(1):147-51.
- Immunohistochemical characterization of human olfactory tissue. Laryngoscope. 2011 Aug; 121(8):1687-701.
- Radiology quiz case 3. Arch Otolaryngol Head Neck Surg. 2011 Apr 18; 137(4):406.
- Radiology quiz case 3. Organizing hematoma of maxillary sinus (OHMS). Arch Otolaryngol Head Neck Surg. 2011 Apr; 137(4):406.
- Management of a long-standing organic intracranial foreign body. Skull Base. 2010 Nov; 20(6):487-90.
- An atypical case of chronic invasive fungal sinusitis and its management. Otolaryngol Head Neck Surg. 2010 Jan; 142(1):150-1.
- Cigarette smoke combined with Toll-like receptor 3 signaling triggers exaggerated epithelial regulated upon activation, normal T-cell expressed and secreted/CCL5 expression in chronic rhinosinusitis. J Allergy Clin Immunol. 2008 Dec; 122(6):1145-1153.e3.
- Radiology quiz case 1. Anaplastic thyroid carcinoma. Arch Otolaryngol Head Neck Surg. 2008 Apr; 134(4):442, 444.
- Decreased nasal mucosal sensitivity in older subjects. Am J Rhinol. 2006 May-Jun; 20(3):364-8.
- An updated review of clinical olfaction. Curr Opin Otolaryngol Head Neck Surg. 2006 Feb; 14(1):23-8.
- Abnormalities of axon growth in human olfactory mucosa. Laryngoscope. 2005 Dec; 115(12):2144-54.
- Lack of significant correlation between rhinosinusitis symptoms and specific regions of sinus computer tomography scans. Am J Rhinol. 2005 Jul-Aug; 19(4):382-7.
- Grisel's syndrome: a case report and review of the literature. Int J Pediatr Otorhinolaryngol. 2005 Dec; 69(12):1689-92.
- Olfactory loss as a result of toxic exposure. Otolaryngol Clin North Am. 2004 Dec; 37(6):1185-207.
- Matrix metalloproteinase expression in the olfactory epithelium. Neuroreport. 2003 Jun 11; 14(8):1135-40.
- Anosmia: diagnosis and management. Curr Opin Otolaryngol Head Neck Surg. 2003 Feb; 11(1):54-60.
- Olfactory epithelium grafts in the cerebral cortex: an immunohistochemical analysis. Laryngoscope. 2001 Nov; 111(11 Pt 1):1964-9.
- Rhinotopy is disrupted during the re-innervation of the olfactory bulb that follows transection of the olfactory nerve. Chem Senses. 2001 May; 26(4):359-69.
- An immunochemical, ultrastructural, and developmental characterization of the horizontal basal cells of rat olfactory epithelium. J Comp Neurol. 1995 Dec 04; 363(1):129-46.
- Multisegmental analyses of acoustic startle in the flying cricket (Teleogryllus oceanicus): kinematics and electromyography. J Exp Biol. 1992 Aug; 169:19-36.
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