A5053954475- Head and Neck Surgical Oncology
- Hearing, Cochlea, Tinnitus, Genetics
- Cerebrospinal fluid and hydrocephalus
- Meningioma and schwannoma management
- Ear Surgery and Otitis Media
- Neurosurgical Procedures and Complications
- Hearing Loss and Rehabilitation
- Facial Nerve Paralysis Treatment and Research
- Ear and Head Tumors
- Obstructive Sleep Apnea Research
- Tracheal and airway disorders
- Ubiquitin and proteasome pathways
- Cerebral Venous Sinus Thrombosis
- Neurofibromatosis and Schwannoma Cases
- Bone Tumor Diagnosis and Treatments
- Neuroscience of respiration and sleep
- Developmental Biology and Gene Regulation
- Congenital heart defects research
- Burn Injury Management and Outcomes
- Cardiac tumors and thrombi
- Noise Effects and Management
- Congenital Ear and Nasal Anomalies
- Infection Control and Ventilation
- Underwater Vehicles and Communication Systems
- Genetics and Neurodevelopmental Disorders
Indiana University School of Medicine
2016-2025
Indiana University – Purdue University Indianapolis
2016-2025
Indiana University
2015-2024
Neurological Surgery
2018-2024
University School
2020-2024
Google (United States)
2022-2023
Tharawal Aboriginal
2022
Indiana University Indianapolis
2020-2021
GTx (United States)
2019
Indiana University Bloomington
2018
Huntington's disease (HD) and other polyglutamine (polyQ) neurodegenerative diseases are characterized by neuronal accumulation of the protein, suggesting that cellular ability to handle abnormal proteins is compromised. As both a cochaperone ubiquitin ligase, C-terminal Hsp70 (heat shock protein 70)-interacting (CHIP) links two major arms quality control, molecular chaperones, ubiquitin-proteasome system. Here, we demonstrate CHIP suppresses polyQ aggregation toxicity in transfected cell...
Patients with large vestibular schwannomas are at high risk of poor facial nerve (cranial VII [CNVII]) function after surgery. Subtotal resection potentially offers better outcome, but may lead to higher tumor regrowth.To assess long-term CNVII and regrowth in patients schwannomas.Prospective multicenter nonrandomized cohort study schwannoma ≥2.5 cm who received gross total resection, near or subtotal resection. radiation if remnant showed signs regrowth.Seventy-three had adequate follow-up...
To determine the national rates of spontaneous CSF leaks and to association with risk factors.Retrospective review from 2002 2012.University HealthSystem Consortium (UHC) database 127 leading academic medical centers in United States (81 participated all years study).Those who underwent craniotomy for leak repair UHC those have undergone at one center.Assessment procedure code patient demographics 2012.National each year, relation U.S. regional obesity rates, proportion patients coincident...
Mutations in the gene encoding type II transmembrane protease 3 (TMPRSS3) cause human hearing loss, although underlying mechanisms that result TMPRSS3-related loss are still unclear. We combined use of stem cell-derived inner ear organoids with single-cell RNA sequencing to investigate role TMPRSS3. Defective Tmprss3 leads hair cell apoptosis without altering development cells and formation mechanotransduction apparatus. Prior degeneration, Tmprss3-KO demonstrate reduced numbers BK channels...
Post-translational modification of proteins regulates many cellular processes. Some modifications, including N-linked glycosylation, serve multiple functions. For example, the attachment glycans to nascent in endoplasmic reticulum facilitates proper folding, whereas retention high mannose on misfolded glycoproteins serves as a signal for retrotranslocation and ubiquitin-mediated proteasomal degradation. Here we examine substrate specificity only family ubiquitin ligase subunits thought...
To determine the thickness of calvarium in patients with spontaneous cerebrospinal fluid (CSF) leaks.Case control study.University Iowa Hospitals and Clinics.Those a confirmed CSF leak compared to non-obese (body mass index, BMI < 30) obese (BMI ≥ cochlear implant (CI) groups. All had have temporal bone CT scans that fit specified criteria.Bilateral volumetric analysis squamous zygoma all patients. Assessment patient age, sex, BMI, medical comorbidities.Assessment average groups.The leaks...
To determine the efficacy and morbidity of repairing spontaneous cerebrospinal fluid (CSF) leaks with middle cranial fossa (MCF) approach without use a lumbar drain (LD), as perioperative LD remains controversial.Retrospective review from 2003 to 2015.University Iowa Hospitals Clinics Indiana University Health Center.Those confirmed lateral skull base CSF and/or encephaloceles.MCF for repair leak encephalocele drain. Assessment patient age, sex, body mass index (BMI), medical...
Cochlear implants (CI) have revolutionized the treatment of patients with severe to profound sensory hearing loss by providing a method bypassing normal directly stimulate auditory nerve. A further advance in field has been introduction “hearing preservation” surgery, whereby CI electrode array (EA) is carefully inserted spare damage delicate anatomy and function cochlea. Preserving residual inner ear allows receive maximal benefit from combine electric stimulation acoustic hearing, offering...
Objective Evaluate postoperative opening pressures (OP) on lumbar puncture (LP) and polysomnogram (PSG) findings in patients who underwent middle cranial fossa (MCF) repair with lateral spontaneous cerebrospinal fluid (sCSF) leaks. Study Design Retrospective cohort study. Setting Tertiary referral center. Interventions MCF of sCSF leak, PSG, LP. Main Outcome Measures Prevalence intracranial hypertension (IH; LP OP >25 cm H 2 O), obstructive sleep apnea (OSA) (apnea–hypopnea index [AHI]...
Little is known about the role of protein quality control in inner ear. We now report selective cochlear degeneration mice deficient Fbx2, a ubiquitin ligase F-box with specificity for high-mannose glycoproteins (Yoshida et al., 2002). Originally described as brain-enriched (Erhardt 1998), Fbx2 also highly expressed organ Corti, which it has been called Corti 1 (Thalmann 1997). Mice targeted deletion Fbxo2 develop age-related hearing loss beginning at 2 months. Cellular begins epithelial...
NMDA receptors (NMDARs) play an essential role in some forms of synaptic plasticity, learning, and memory. Therefore, these are highly regulated with respect to their localization, activation, abundance both within on the surface mammalian neurons. Fundamental questions remain, however, regarding how this complex regulation is achieved. Using cell-based models F-box Only Protein 2 ( Fbxo2 ) knock-out mice, we found that ubiquitin ligase substrate adaptor protein Fbxo2, previously reported...
To determine the prevalence of obstructive sleep apnea (OSA) in a prospective cohort patients with spontaneous CSF (sCSF) leaks temporal bone.Prospective study.Tertiary referral center.Consecutive sCSF leak (21) over 3-year period. Four presented history OSA and 17 were prospectively offered polysomnogram (PSG) testing during initial clinic encounter.Level I PSG.Patient characteristics (age, sex, body mass index), hypopnea index (AHI), presence snoring, hypoxia (oxygen saturation <88% for >5...
Spontaneous cerebrospinal fluid leaks (sCSF-L) of the temporal bone are associated with obesity, calvarial thinning, and obstructive sleep apnea (OSA), incidence has doubled in past decade. It is currently unknown if OSA independently skull thinning.To determine patients have thinner skulls than without OSA.A retrospective cohort study who underwent a level 1 polysomnogram (PSG) also had high-resolution computed tomographic (CT) imaging head from January 2010 to March 2017 at Indiana...
In SCF (Skp1/Cullin/F-box protein) ubiquitin ligases, substrate specificity is conferred by a diverse array of F-box proteins. Only in fully assembled complexes, it believed, can substrates bound to proteins become ubiquitinated. Here we show that Fbx2, brain-enriched protein implicated the ubiquitination glycoproteins discarded from endoplasmic reticulum, binds co-chaperone/ubiquitin ligase CHIP (C terminus Hsc-70-interacting through unique N-terminal PEST domain Fbx2. facilitates and...
Objective: Determine if patients with increased opening pressure (OP) on lumbar puncture (LP) have thinner calvaria and skull bases. Study Design: Retrospective cohort study. Setting: Tertiary referral center. Patients: Patients (≥18 yr of age) who had a recorded OP LP high-resolution computed tomography imaging the head. Patient age, sex, body mass index were calculated. Intracranial hypertension (IH) was defined an OP≥25 cm-H 2 O low intracranial OP<15 O. Intervention: Measurement...
Abstract The inner ear is derived from the otic placode, one of numerous cranial sensory placodes that emerges pre-placodal ectoderm (PPE) along its anterior-posterior axis. However, molecular dynamics underlying how PPE regionalized are poorly resolved. We used stem cell-derived organoids to investigate effects Wnt signaling on early differentiation and found modulating significantly increased organoid induction efficiency reproducibility. Alongside single-cell RNA sequencing, our data...
Objectives To determine the safety and effectiveness of middle cranial fossa (MCF) approach in repairing spontaneous cerebrospinal fluid (sCSF) leaks. Study Design Retrospective cohort study. Methods Patient with sCSF leaks repaired by MCF between January 1, 2014 August 31, 2019 were included. Demographic information, clinical surgical findings, postoperative outcomes recorded. Results The (n = 45) included 24 tegmen repairs multilayer reconstruction using hydroxyapatite cement 21 cases...
Adeno-associated virus (AAV)-mediated gene transfer has shown promise in rescuing mouse models of genetic hearing loss, but how viral capsid and promoter selection affects efficacy is poorly characterized. Here, we tested combinations AAVs promoters to deliver Tmprss3, mutations which are associated with loss humans. Tmprss3tm1/tm1 mice display severe cochlear hair cell degeneration, auditory brainstem responses, delayed spiral ganglion neurons. Under the ubiquitous CAG AAV-KP1 capsid,...
To compare differences in audiologic outcomes between slim modiolar electrode (SME) CI532 and lateral wall (SLW) CI522 cochlear implant recipients.Retrospective cohort study.Tertiary academic hospital.Comparison of postoperative AzBio sentence scores quiet (percentage correct) adult recipients with SME or SLW matched for preoperative aided unaided pure tone average.Patients (n = 52) patients 37) had a similar mean (SD) age (62.0 [18.2] vs 62.6 [14.6] years, respectively), average (55.9...