A5037332686- Hearing, Cochlea, Tinnitus, Genetics
- TGF-β signaling in diseases
- Hearing Loss and Rehabilitation
- Cancer, Hypoxia, and Metabolism
- Vestibular and auditory disorders
- Single-cell and spatial transcriptomics
- Cancer-related molecular mechanisms research
- melanin and skin pigmentation
- Cancer Research and Treatments
- Radiomics and Machine Learning in Medical Imaging
- Genetic factors in colorectal cancer
- Gastric Cancer Management and Outcomes
- Epigenetics and DNA Methylation
- Inflammatory mediators and NSAID effects
- Pancreatic and Hepatic Oncology Research
- Peptidase Inhibition and Analysis
- RNA regulation and disease
- Liver Disease Diagnosis and Treatment
- Cell Adhesion Molecules Research
- Gut microbiota and health
- Colorectal Cancer Treatments and Studies
- Cellular transport and secretion
- Alcohol Consumption and Health Effects
- Neurofibromatosis and Schwannoma Cases
- Facial Nerve Paralysis Treatment and Research
National Institute on Deafness and Other Communication Disorders
2019-2025
National Institutes of Health
2019-2025
George Washington University
2016-2019
The University of Texas Health Science Center at San Antonio
2012
We present an integromic analysis of gene alterations that modulate transforming growth factor β (TGF-β)-Smad-mediated signaling in 9,125 tumor samples across 33 cancer types The Cancer Genome Atlas (TCGA). Focusing on genes encode mediators and regulators TGF-β signaling, we found at least one genomic alteration (mutation, homozygous deletion, or amplification) 39% samples, with highest frequencies gastrointestinal cancers. identified mutation hotspots ligands (BMP5), receptors (TGFBR2,...
The stria vascularis (SV) generates the endocochlear potential (EP) in inner ear and is necessary for proper hair cell mechanotransduction hearing. While channels belonging to SV types are known play crucial roles EP generation, relatively little about gene regulatory networks that underlie ability of generate maintain EP. Using single nucleus RNA-sequencing, we identify validate rare populations SV. Furthermore, establish a basis understanding molecular mechanisms underlying function by...
Hearing loss is a problem that impacts significant proportion of the adult population. Cochlear hair cell (HC) due to loud noise, chemotherapy and aging major underlying cause. A these individuals are dissatisfied with available treatment options which include hearing aids cochlear implants. An alternative approach restore would be regenerate HCs. Such therapy require recapitulation complex architecture organ Corti, necessitating regeneration both mature HCs supporting cells (SCs)....
Abstract Disruption of the TGF-β pathway is associated with liver fibrosis and suppression tumorigenesis, conditions low Vitamin D (VD) levels. However, potential contributions VD to tumor progression in context signaling remain unexplored. Our analyses deprivation (VDD) vivo models formation revealed striking three-fold increases burden Smad3 +/− mice, a increase TLR7 expression compared controls. ChIP transcriptional assays confirm binding at two promoter SBE sites. Molecular interactions...
Abstract The stria vascularis (SV) in the cochlea generates and maintains endocochlear potential, thereby playing a pivotal role normal hearing. Knowing transcriptional profiles gene regulatory networks of SV cell types establishes basis for studying mechanism underlying SV-related hearing loss. While we have previously characterized expression major adult mouse, rare remained elusive due to limitation capture single-cell RNA-Seq. these homeostatic function remain largely undefined. In this...
Abstract The stria vascularis (SV) is a stratified epithelium in the lateral wall of mammalian cochlea, responsible for both endolymphatic ion homeostasis and generation endocochlear potential (EP) critical normal hearing. SV has three layers consisting predominantly basal, intermediate, marginal cells. Intermediate cells form an intricate interdigitated network cell projections making discrimination challenging. To enable intermediate visualization, we engineered by BAC transgenesis,...
The stria vascularis (SV) is an essential component of the inner ear that regulates ionic environment required for hearing. SV degeneration disrupts cochlear homeostasis, leading to irreversible hearing loss, yet a comprehensive understanding SV, and consequently therapeutic availability degeneration, lacking. We developed whole-tissue explant model from neonatal mature mice create platform advancing research. validated our by demonstrating proliferative behavior in vitro mimics vivo. also...
Hereditary deafness and retinal dystrophy are each genetically heterogenous clinically variable. Three small unrelated families segregating the combination of were studied by exome sequencing (ES). The proband Family 1 was found to be compound heterozygous for NM_004525.3: LRP2: c.5005A > G, p.(Asn1669Asp) c.149C p.(Thr50Ser). In 2, two sisters LRP2 variants, p.(Tyr3933Cys) an experimentally confirmed c.7715 + 3A T consensus splice-altering variant. 3, is a donor splice site variant...
Mutational processes and signatures that drive early tumorigenesis are centrally important for cancer prevention. Yet, to date, biomarkers risk factors polyps (adenomas) inordinately rapidly develop into colon remain poorly defined. Here, we describe surprisingly high mutational profiles through whole-genome sequence (WGS) analysis in 2 of 4 pairs benign colorectal adenoma tissue samples. Unsupervised hierarchical clustered transcriptomic a further 7 adenomas reveals distinct regardless...
Human pathogenic variants of TBC1D24 are associated with clinically heterogeneous phenotypes, including recessive nonsyndromic deafness DFNB86, dominant DFNA65, seizure accompanied by deafness, a variety isolated phenotypes and DOORS syndrome, characterized onychodystrophy, osteodystrophy, intellectual disability seizures. Thirty-five human have been reported. However, functions in the inner ear pathophysiology TBC1D24-related unknown. In this study, novel splice-site variant c.965 + 1G > A...
Background Treatment of many types hearing instability in humans, including sudden sensorineural loss, Meniere's disease, and autoimmune inner ear rely heavily on the utilization corticosteroids delivered both by oral transtympanic routes. Despite this use, there is heterogeneity response to treatment with humans these diseases. The mechanisms which exert their effect cell they effects remain poorly characterized. In study, we localize steroid-responsive genes cochlear using previously...
The stria vascularis (SV), part of the blood-labyrinth barrier, is an essential component inner ear that regulates ionic environment required for hearing. SV degeneration disrupts cochlear homeostasis, leading to irreversible hearing loss, yet a comprehensive understanding SV, and consequently therapeutic availability degeneration, lacking. We developed whole-tissue explant model from neonatal adult mice create robust platform research. validated our by demonstrating proliferative behaviour
Abstract The inflammatory foreign body response (FBR) following cochlear implantation (CI) can negatively impact CI outcomes, including increased electrode impedances. This study aims to investigate the long-term efficacy of dexamethasone eluting implant and locally delivered dexamethasone, a potent anti-inflammatory glucocorticoid on intracochlear FBR electrical impedance post-implantation in murine model human subjects. left ears CX3CR1 +/GFP Thy1 +/YFP (macrophage-neuron dual reporter)...
Corticosteroids, oral or transtympanic, remain the mainstay for inner ear diseases characterized by hearing fluctuation sudden changes in hearing, including sensorineural loss (SSNHL), Meniere's disease (MD), and autoimmune (AIED). Despite their use across these diseases, rate of complete recovery remains low, results literature demonstrates significant heterogeneity with respect to effect corticosteroids, suggesting a need identify more efficacious treatment options. Previously, our group...
Hypothesis: Proteins enriched in the perilymph proteome of Meńier̀e disease (MD) patients may identify affected cell types. Utilizing single-cell transcriptome datasets from mammalian cochlea, we hypothesize that these proteins can be localized to specific cochlear Background: The limited understanding human inner ear pathologies and their associated biomolecular variations hinder efforts develop disease-specific diagnostics therapeutics. Perilymph sampling analysis is now enabling further...
Objective: To find a more objective method of assessing which patients should be screened for vestibular schwannoma (VS) with magnetic resonance imaging (MRI) using deep-learning algorithm to assess clinical and audiometric data. Materials Methods: Clinical data were collected 592 who received an audiogram between January 2015 2020 at Duke University Health Center without VS confirmed by MRI. These analyzed deep learning-based analysis determine if the need MRI screening could assessed...
Abstract The stria vascularis (SV) is a stratified epithelium in the lateral wall of mammalian cochlea, responsible for both endolymphatic ion homeostasis and generation endocochlear potential (EP) critical normal hearing. SV has three layers consisting predominantly basal, intermediate, marginal cells. Intermediate cells form an intricate interdigitated network cell projections making discrimination challenging. To enable intermediate visualization, we engineered by BAC transgenesis,...
Deafness in vertebrates is associated with variants of hundreds genes. Yet, many mutant genes causing rare forms deafness remain to be discovered. A consanguineous Pakistani family segregating nonsyndromic two sibships were studied using microarrays and exome sequencing. 1.2 Mb locus (DFNB128) on chromosome 5q11.2 encompassing six was identified. In one the this family, a novel homozygous recessive variant NM_005921.2:c.4460G>A p.(Arg1487His) kinase domain
Abstract Background: TGF-β/SMAD signaling is a crucial, often contradictory regulator in multiple stages of liver disease that include inflammation, cirrhosis and development HCC as well other cancers. The context-specific role this pathway treatment strategies has yet to be clarified. Therefore, understanding the roles across broad cancer types critical towards deciphering complexities pathway. Methods: We followed our previous analysis HCCs, by extending examining TGF-β 33 TCGA tumor 9125...