Scholars@Duke
Bradley John Goldstein

Bradley John Goldstein

Professor of Head and Neck Surgery & Communication Sciences
Rhinology and Skull Base Surgery
Duke South Yellow Zone #4000, DUMC Box 3805, Durham, NC 27710
40 Duke Medicine Circle, DUMC Box 3805, Durham, NC 27710

Selected Publications

Utility of Existing Patient-Reported Outcome Measures for Identifying Non-Rhinogenic Facial Pain.

Journal Article Laryngoscope · March 22, 2025 OBJECTIVE: Facial pain/pressure is often non-rhinogenic and migraine-related in etiology. However, this is frequently misdiagnosed as sinusitis, leading to inappropriate antibiotic utilization and unnecessary procedures. We assessed the utility of the 3-It ... Full text Link to item Cite

Olfactory neuroblastoma mimics molecular heterogeneity and lineage trajectories of small-cell lung cancer.

Journal Article Cancer Cell · June 10, 2024 The olfactory epithelium undergoes neuronal regeneration from basal stem cells and is susceptible to olfactory neuroblastoma (ONB), a rare tumor of unclear origins. Employing alterations in Rb1/Trp53/Myc (RPM), we establish a genetically engineered mouse m ... Full text Link to item Cite

Long-term olfactory loss post-COVID-19: Pathobiology and potential therapeutic strategies.

Journal Article World J Otorhinolaryngol Head Neck Surg · June 2024 An acute loss of smell emerged as a striking symptom present in roughly half of the people infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in the early phases of the COVID-19 pandemic. In most COVID-19 patients, olfacti ... Full text Link to item Cite

Polycomb repressive complex 2 regulates basal cell fate during adult olfactory neurogenesis.

Journal Article Stem Cell Reports · November 14, 2023 Adult neurogenesis occurs in the mammalian olfactory epithelium to maintain populations of neurons that are vulnerable to injury yet essential for olfaction. Multipotent olfactory basal stem cells are activated by damage, although mechanisms regulating lin ... Full text Link to item Cite

Deconstructing Olfactory Epithelium Developmental Pathways in Olfactory Neuroblastoma.

Journal Article Cancer Res Commun · June 2023 UNLABELLED: Olfactory neuroblastoma is a rare tumor arising from the olfactory cleft region of the nasal cavity. Because of the low incidence of this tumor, as well as an absence of established cell lines and murine models, understanding the mechanisms dri ... Full text Link to item Cite

Persistent post-COVID-19 smell loss is associated with immune cell infiltration and altered gene expression in olfactory epithelium.

Journal Article Sci Transl Med · December 21, 2022 SARS-CoV-2 causes profound changes in the sense of smell, including total smell loss. Although these alterations are often transient, many patients with COVID-19 exhibit olfactory dysfunction that lasts months to years. Although animal and human autopsy st ... Full text Link to item Cite

Endoscopic Sinus Surgery in Older Patients With Significant Medical Comorbidities.

Journal Article Am J Rhinol Allergy · September 2022 BACKGROUND: Endoscopic sinus surgery (ESS) offers excellent outcomes for patients with chronic rhinosinusitis (CRS) in the general population. It is unclear whether older patients with significant medical comorbidities experience similar benefits. OBJECTIV ... Full text Link to item Cite

Persistent post-COVID-19 smell loss is associated with inflammatory infiltration and altered olfactory epithelial gene expression.

Journal Article bioRxiv · April 18, 2022 Most human subjects infected by SARS-CoV-2 report an acute alteration in their sense of smell, and more than 25% of COVID patients report lasting olfactory dysfunction. While animal studies and human autopsy tissues have suggested mechanisms underlying acu ... Full text Link to item Cite

International consensus statement on allergy and rhinology: Olfaction.

Journal Article Int Forum Allergy Rhinol · April 2022 BACKGROUND: The literature regarding clinical olfaction, olfactory loss, and olfactory dysfunction has expanded rapidly over the past two decades, with an exponential rise in the past year. There is substantial variability in the quality of this literature ... Full text Link to item Cite

Aging-related olfactory loss is associated with olfactory stem cell transcriptional alterations in humans.

Journal Article J Clin Invest · February 15, 2022 BACKGROUNDPresbyosmia, or aging-related olfactory loss, occurs in a majority of humans over age 65 years, yet remains poorly understood, with no specific treatment options. The olfactory epithelium (OE) is the peripheral organ for olfaction and is subject ... Full text Link to item Cite

Survival Outcomes in Sinonasal Poorly Differentiated Squamous Cell Carcinoma.

Journal Article Laryngoscope · April 2021 OBJECTIVE: Sinonasal squamous cell carcinoma (SCC) is rare with no consensus on treatment regimen. Our goal is to analyze treatment outcomes in poorly differentiated SCC (PDSCC) using a large national database. STUDY DESIGN: Retrospective database study. M ... Full text Link to item Cite

On the in vivo origin of human nasal mesenchymal stem cell cultures.

Journal Article Laryngoscope Investig Otolaryngol · December 2020 OBJECTIVES: Mesenchymal stem cells (MSCs), classically expanded in culture from bone marrow, are of broad interest to the regenerative medicine community. Human nasal turbinate mesenchymal-like stem cell cultures have also been described, defined by an in ... Full text Link to item Cite

Identifying Treatments for Taste and Smell Disorders: Gaps and Opportunities.

Journal Article Chem Senses · October 9, 2020 The chemical senses of taste and smell play a vital role in conveying information about ourselves and our environment. Tastes and smells can warn against danger and also contribute to the daily enjoyment of food, friends and family, and our surroundings. O ... Full text Open Access Link to item Cite

Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia.

Journal Article Sci Adv · July 31, 2020 Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) - the causal agent in COVID-19 - affects olfaction directly, by infecting olfactory sensory neurons or their targets in th ... Full text Link to item Cite

Acute N-Acetylcysteine Administration Ameliorates Loss of Olfactory Neurons Following Experimental Injury In Vivo.

Journal Article Anat Rec (Hoboken) · March 2020 The olfactory epithelium (OE) is the peripheral organ for the sense of smell, housing primary sensory neurons that project axons from the nose to the brain. Due to the presence of a basal stem cell niche, the adult mammalian OE is a dynamic tissue capable ... Full text Link to item Cite

Single-cell analysis of olfactory neurogenesis and differentiation in adult humans.

Journal Article Nat Neurosci · March 2020 The presence of active neurogenic niches in adult humans is controversial. We focused attention to the human olfactory neuroepithelium, an extracranial site supplying input to the olfactory bulbs of the brain. Using single-cell RNA sequencing analyzing 28, ... Full text Link to item Cite

Loss of BMI1 in mature olfactory sensory neurons leads to increased olfactory basal cell proliferation.

Journal Article Int Forum Allergy Rhinol · September 2019 BACKGROUND: Damage to olfactory sensory neurons (OSNs), situated within the neuroepithelium of the olfactory cleft, may be associated with anosmia. Although their direct contact with the nasal airspace make OSNs vulnerable to injury and death, multiple mec ... Full text Link to item Cite

Cell-Based Therapy Restores Olfactory Function in an Inducible Model of Hyposmia.

Journal Article Stem Cell Reports · June 11, 2019 Stem cell-based therapies have been proposed as a strategy to replace damaged tissues, especially in the nervous system. A primary sensory modality, olfaction, is impaired in 12% of the US population, but lacks treatment options. We report here the develop ... Full text Link to item Cite

Multiple polycomb epigenetic regulatory proteins are active in normal and regenerating adult olfactory epithelium.

Journal Article Laryngoscope Investig Otolaryngol · October 2018 OBJECTIVES: To investigate epigenetic mechanisms contributing to regulation of cellular renewal and neurogenesis in adult olfactory epithelium (OE). STUDY DESIGN: Prospective basic science study. METHODS: Olfactory basal cell cultures were prepared from ad ... Full text Link to item Cite

Osteopontin deficiency ameliorates Alport pathology by preventing tubular metabolic deficits.

Journal Article JCI Insight · March 22, 2018 Alport syndrome is a rare hereditary renal disorder with no etiologic therapy. We found that osteopontin (OPN) is highly expressed in the renal tubules of the Alport mouse and plays a causative pathological role. OPN genetic deletion ameliorated albuminuri ... Full text Link to item Cite

Olfactory epithelium: Cells, clinical disorders, and insights from an adult stem cell niche.

Journal Article Laryngoscope Investig Otolaryngol · February 2018 UNLABELLED: Disorders causing a loss of the sense of smell remain a therapeutic challenge. Basic research has, however, greatly expanded our knowledge of the organization and function of the olfactory system. This review describes advances in our understan ... Full text Link to item Cite

Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Journal Article J Gerontol A Biol Sci Med Sci · October 12, 2017 BACKGROUND: Aging frailty, characterized by decreased physical and immunological functioning, is associated with stem cell depletion. Human allogeneic mesenchymal stem cells (allo-hMSCs) exert immunomodulatory effects and promote tissue repair. METHODS: Th ... Full text Link to item Cite

Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty.

Journal Article J Gerontol A Biol Sci Med Sci · October 12, 2017 BACKGROUND: Impaired endogenous stem cell repair capacity is hypothesized to be a biologic basis of frailty. Therapies that restore regenerative capacity may therefore be beneficial. This Phase 1 study evaluated the safety and potential efficacy of intrave ... Full text Link to item Cite

Histologic changes of mesenchymal stem cell repair of tympanic membrane perforation.

Journal Article Acta Otolaryngol · April 2017 CONCLUSION: Mesenchymal stem-cells are good candidates for cell-therapy of chronic tympanic membranes perforations. OBJECTIVES: To determine the effects of cell-based therapy in tympanic membrane perforations. METHODS: Young C57BL/6 mice were anesthetized ... Full text Link to item Cite

Differential expression of microRNAs among cell populations in the regenerating adult mouse olfactory epithelium.

Journal Article PLoS One · 2017 Despite a robust capacity for adult neurogenesis in the olfactory epithelium (OE), olfactory sensory losses are common. Identification of mechanisms regulating adult OE neurogenesis is, therefore, of interest. MicroRNAs (miRNAs) are broadly important in re ... Full text Link to item Cite

Contribution of Polycomb group proteins to olfactory basal stem cell self-renewal in a novel c-KIT+ culture model and in vivo.

Journal Article Development · December 1, 2016 Olfactory epithelium (OE) has a lifelong capacity for neurogenesis due to the presence of basal stem cells. Despite the ability to generate short-term cultures, the successful in vitro expansion of purified stem cells from adult OE has not been reported. W ... Full text Link to item Cite

Effects of Cell-Based Therapy for Treating Tympanic Membrane Perforations in Mice.

Journal Article Otolaryngol Head Neck Surg · June 2016 OBJECTIVE: To investigate the effectiveness of scaffold-embedded mesenchymal stem cells (MSCs) as a topical treatment for healing tympanic membrane perforations (TMPs) in a mouse model. STUDY DESIGN: Prospective animal study. SETTING: Experimental. SUBJECT ... Full text Link to item Cite

Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty.

Journal Article Oncotarget · March 15, 2016 Frailty is a syndrome associated with reduced physiological reserves that increases an individual's vulnerability for developing increased morbidity and/or mortality. While most clinical trials have focused on exercise, nutrition, pharmacologic agents, or ... Full text Link to item Cite

Differentiation potential of individual olfactory c-Kit+ progenitors determined via multicolor lineage tracing.

Journal Article Dev Neurobiol · March 2016 Olfactory tissue undergoes lifelong renewal, due to the presence of basal neural stem cells. Multiple categories of globose basal stem cells have been identified, expressing markers such as Lgr5, Ascl1, GBC-2, and c-Kit. The differentiation potential of in ... Full text Link to item Cite

Olfaction: Anatomy, function, pathophysiology and diseases

Chapter · April 1, 2015 The olfactory receptor epithelium functions to transmit odor information from the nose to the brain. Here, we review the anatomy and physiology of the olfactory system. We focus on the organization of the peripheral olfactory apparatus, and the process of ... Cite

The effect of endoscopic olfactory cleft polyp removal on olfaction.

Journal Article Am J Rhinol Allergy · 2015 BACKGROUND: The presence of olfactory cleft polyps in chronic rhinosinusitis with nasal polyposis is well documented, but the effect of endoscopic olfactory cleft polyp surgery on olfaction, versus observation, has not been well studied. This analysis asse ... Full text Link to item Cite

Prevalence of mutations in GJB2, SLC26A4, and mtDNA in children with severe or profound sensorineural hearing loss in southwestern China.

Journal Article Genet Test Mol Biomarkers · January 2015 AIM: To study the distribution characteristics of common mutations in the GJB2, SLC26A4, and mtDNA genes in children with severe or profound sensorineural hearing loss (SNHL) in southwestern China. MATERIALS AND METHODS: A total of 1,164 individuals were r ... Full text Link to item Cite

Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons.

Journal Article J Comp Neurol · January 1, 2015 The olfactory epithelium houses chemosensory neurons, which transmit odor information from the nose to the brain. In adult mammals, the olfactory epithelium is a uniquely robust neuroproliferative zone, with the ability to replenish its neuronal and non-ne ... Full text Link to item Cite

Adult human nasal mesenchymal-like stem cells restore cochlear spiral ganglion neurons after experimental lesion.

Journal Article Stem Cells Dev · March 1, 2014 A loss of sensory hair cells or spiral ganglion neurons from the inner ear causes deafness, affecting millions of people. Currently, there is no effective therapy to repair the inner ear sensory structures in humans. Cochlear implantation can restore input ... Full text Link to item Cite

Introduction

Journal Article Operative Techniques in Otolaryngology - Head and Neck Surgery · January 1, 2014 Full text Cite

Adult human nasal mesenchymal stem cells have an unexpected broad anatomic distribution.

Journal Article Int Forum Allergy Rhinol · July 2013 BACKGROUND: The olfactory epithelium is a self-renewing tissue, able to produce new neurons as needed from stem and progenitor cells in its basal layers. In addition, there exists a mesenchymal-like stem cell (MSC) located within the underlying lamina prop ... Full text Link to item Cite

Modern management of chylous leak following head and neck surgery: a discussion of percutaneous lymphangiography-guided cannulation and embolization of the thoracic duct.

Journal Article Otolaryngol Clin North Am · December 2008 High-output chylous leak beyond 5 to 7 days of conservative medical treatment should be treated promptly to avoid the risk for nutritional and imunologic depletion. Given the effectiveness and low morbidity of this minimally invasive treatment, this is a r ... Full text Link to item Cite

An atypical case of fatal zygomycosis: simultaneous cutaneous and laryngeal infection in a patient with a non-neutropenic solid prostatic tumor.

Journal Article Ear Nose Throat J · March 2008 We describe what we believe is the first reported case of simultaneous highly invasive cutaneous and laryngopharyngeal zygomycosis in a non-neutropenic, nondiabetic but immunosuppressed patient with prostate cancer. An invasive fungal process was not suspe ... Link to item Cite

The difficult airway: Implications for the otolaryngologist-head and neck surgeon

Journal Article Operative Techniques in Otolaryngology - Head and Neck Surgery · June 1, 2007 Clinical situations arise in which maintenance of adequate ventilation becomes technically difficult, often either in an emergency setting or perioperatively. The otolaryngologist-head and neck surgeon is frequently called upon to provide expertise in airw ... Full text Cite

Malignant tumors of the sinonasal tract

Journal Article Journal of Postgraduate Medicine · January 1, 2005 Cite

Future directions in chemosensory research.

Journal Article Otolaryngol Clin North Am · December 2004 The past two decades have witnessed phenomenal growth in chemosensory research in the basic sciences and clinical studies. Although chemosensory disorders today are recognized more widely for their marked impacts on QOL and public safety, the increased res ... Full text Link to item Cite

Cloning and characterization of SLP3: a novel member of the stomatin family expressed by olfactory receptor neurons.

Journal Article J Assoc Res Otolaryngol · March 2003 The detection of odorants with high sensitivity and specificity utilizes specialized transduction proteins that may be assembled into complexes to afford enhanced speed and efficiency in olfactory neurons. We have used a differential cDNA screening techniq ... Full text Link to item Cite

Multifocal papillary thyroid carcinoma arising in a lingual thyroid: a case report.

Journal Article Arch Otolaryngol Head Neck Surg · October 2002 We report the first case (to our knowledge) of a multifocal papillary thyroid carcinoma arising in a lingual thyroid. The patient underwent a transcervical, transhyoid approach for excision, followed by radioiodine ablation, with excellent functional and o ... Full text Link to item Cite

Adult olfactory epithelium contains multipotent progenitors that give rise to neurons and non-neural cells.

Journal Article J Comp Neurol · November 2, 1998 We have infused replication-incompetent retroviral vectors into the nasal cavity of adult rats 1 day after exposure to the olfactotoxic gas methyl bromide (MeBr) to assess the lineage relationships of cells in the regenerating olfactory epithelium. The vas ... Link to item Cite

Transplantation of multipotent progenitors from the adult olfactory epithelium.

Journal Article Neuroreport · May 11, 1998 Mammalian olfactory epithelium produces new neurons rapidly throughout adulthood. Here, we demonstrate that precursor cells harvested from the adult olfactory epithelium, when transplanted into the nasal mucosa of host rats exposed previously to an olfacto ... Full text Link to item Cite

FGF2 suppresses neuronogenesis of a cell line derived from rat olfactory epithelium.

Journal Article J Neurobiol · October 1997 Neurogenesis continues throughout adulthood in the mammalian olfactory epithelium (OE), and both neurons as well as nonneuronal cells are reconstituted following experimental injury. Underlying the capacity of the OE to replenish its mature elements is a p ... Link to item Cite

Analysis of the globose basal cell compartment in rat olfactory epithelium using GBC-1, a new monoclonal antibody against globose basal cells.

Journal Article J Neurosci · June 15, 1996 The olfactory epithelium (OE) supports ongoing neurogenesis throughout life and regenerates after experimental injury. Although evidence indicates that proliferative cells within the population of globose (light) basal cells (GBCs) give rise to new neurons ... Full text Link to item Cite

Regenerative proliferation in inner ear sensory epithelia from adult guinea pigs and humans.

Journal Article Science · March 12, 1993 Supporting cells in the vestibular sensory epithelia from the ears of mature guinea pigs and adult humans proliferate in vitro after treatments with aminoglycoside antibiotics that cause sensory hair cells to die. After 4 weeks in culture, the epithelia co ... Full text Link to item Cite