A5007868491- Hearing, Cochlea, Tinnitus, Genetics
- RNA regulation and disease
- Virus-based gene therapy research
- Hearing Loss and Rehabilitation
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Connexins and lens biology
- Antimicrobial Peptides and Activities
- Cell Adhesion Molecules Research
- Vestibular and auditory disorders
- Noise Effects and Management
- Viral Infectious Diseases and Gene Expression in Insects
- Connective tissue disorders research
- Cytomegalovirus and herpesvirus research
- CAR-T cell therapy research
- Viral Infections and Immunology Research
- Biochemical Analysis and Sensing Techniques
- Protease and Inhibitor Mechanisms
- Ion Channels and Receptors
- Ubiquitin and proteasome pathways
- S100 Proteins and Annexins
- RNA Interference and Gene Delivery
University of North Carolina at Chapel Hill
2017-2022
Harvard University
2013-2018
Boston Children's Hospital
2013-2018
University of Virginia
2011-2018
Georgetown University Medical Center
2017
MedStar Georgetown University Hospital
2017
Georgetown University
2017
Boston University
2017
MedStar Washington Hospital Center
2017
University of Pennsylvania
2005-2009
Genetic hearing loss accounts for up to 50% of prelingual deafness worldwide, yet there are no biologic treatments currently available. To investigate gene therapy as a potential strategy restoration auditory function in patients with genetic loss, we tested augmentation approach mouse models deafness. We focused on DFNB7/11 and DFNA36, which autosomal recessive dominant deafnesses, respectively, caused by mutations transmembrane channel-like 1 (TMC1). Mice that carry targeted deletion Tmc1...
The cochlear summating potential (SP) to a tone is baseline shift that persists for the duration of burst. It often considered most enigmatic potentials because its magnitude and polarity vary across frequency level origins are uncertain. In this study, we used pharmacology isolate sources SP originating from gerbil cochlea. Animals either had full complement outer inner hair cells (OHCs IHCs) an intact auditory nerve or systemic treatment with furosemide kanamycin (FK) remove cells....
Mammals experience permanent impairments from hair cell (HC) losses, but birds and other non-mammals quickly recover hearing balance senses after supporting cells (SCs) give rise to replacement HCs. Avian HC epithelia express little or no E-cadherin, differences in the thickness of F-actin belts at SC junctions strongly correlate with different species' capacities for replacement, so we investigated junctional cadherins human murine ears. We found strong E-cadherin expression SC–SC that...
Usher syndrome type 2 (USH2) is the predominant form of USH, a leading genetic cause combined deafness and blindness. PDZD7, paralog two USH causative genes, USH1C USH2D (WHRN), was recently reported to be implicated in USH2 non-syndromic deafness. It encodes protein with multiple PDZ domains. To understand biological function PDZD7 pathogenic mechanism caused by mutations, we generated thoroughly characterized Pdzd7 knockout mouse model. The mice exhibit congenital profound deafness, as...
Mutation in the clarin-1 gene (<i>Clrn1</i>) results loss of hearing and vision humans (Usher syndrome III), but role sensory hair cells is unknown. Clarin-1 predicted to be a four transmembrane domain protein similar members tetraspanin family. Mice carrying null mutation (<i>Clrn1</i><sup>−/−</sup>) show cell function possible defect ribbon synapse. We investigated using various <i>in vitro</i> vivo</i> approaches. by immunohistochemistry patch-clamp recordings Ca<sup>2+</sup> currents...
Adeno-associated virus (AAV) vectors have been successfully used in patients with bleeding disorders and blindness. For human liver targeting, two major factors restrict effective AAV transduction after systemic administration of vectors: hepatocyte tropism neutralizing antibodies (Nabs). In this study, we attempted to isolate variants the ability transduce hepatocytes escape Nabs using a directed evolution approach
Hearing and balance depend upon the precise morphogenesis mechanosensory function of stereocilia, specialized structures on apical surface sensory hair cells in inner ear. Previous studies Grxcr1 mutant mice indicated a critical role for this gene control stereocilia dimensions during development. In study, we analyzed expression paralog Grxcr2 mouse evaluated auditory vestibular strains carrying targeted mutations gene. Peak occurs early postnatal development ear GRXCR2 is localized to both...
Sensorineural hearing loss is one of the most common disabilities worldwide. Such prevalence necessitates effective tools for studying molecular workings cochlear cells. One prominent and vector expressing genes interest in research models adeno-associated virus (AAV). However, AAV efficacy transducing cells can vary a number reasons including serotype, species, methodology, oftentimes requires high multiplicity infection which damage sensory Reports other systems suggest multiple approaches...
Abstract Adeno‐associated virus (AAV) is successfully developed as a major gene therapy vector, but it still susceptible to significant delivery limitation specifically when the vector encounters neutralizing antibodies from pre‐existing immune response or at readministration. Here thermoresponsive polymer elastin‐like polypeptides (ELPs) are utilized crosslink with AAV serotypes 2, 8, and 9 polyplex vectors formed by creating shield of nonviral around them in nanoscale. Neutralizing...