A5081441104- Hearing, Cochlea, Tinnitus, Genetics
- Ion channel regulation and function
- Ion Channels and Receptors
- Vestibular and auditory disorders
- Acoustic Wave Phenomena Research
- Hearing Loss and Rehabilitation
- Biochemical Analysis and Sensing Techniques
- RNA and protein synthesis mechanisms
- Neuroscience and Neuropharmacology Research
- RNA Research and Splicing
- Neurobiology and Insect Physiology Research
- Marine animal studies overview
- RNA regulation and disease
- Ear Surgery and Otitis Media
- Force Microscopy Techniques and Applications
- Microfluidic and Bio-sensing Technologies
- Plant and Biological Electrophysiology Studies
- Muscle Physiology and Disorders
- Neuroscience and Neural Engineering
- Genetic Neurodegenerative Diseases
- Mechanical and Optical Resonators
- Retinal Development and Disorders
- Congenital heart defects research
- Animal Vocal Communication and Behavior
- Cellular Mechanics and Interactions
Harvard University
2015-2024
Boston University
2007-2024
Boston VA Research Institute
2021
Howard Hughes Medical Institute
2009-2018
National Heart Lung and Blood Institute
2017
Framingham Heart Study
2007-2017
Hereditary Disease Foundation
2015
Institute of Neurobiology
2015
The Ohio State University
2009
Harvard University Press
1989-2008
For nearly 60 years, the Framingham Heart Study has examined natural history, risk factors, and prognosis of cardiovascular, lung, other diseases. Recruitment Original Cohort began in 1948. Twenty-three years later, 3,548 children Cohort, along with 1,576 their spouses, enrolled Offspring Cohort. Beginning 2002, 4,095 adults having at least one parent Third Generation 103 parents participants who were not previously The objective new recruitment was to complement phenotypic genotypic...
Hair cells, the primary receptors of auditory, vestibular, and lateral-line sensory systems, produce electrical signals in response to mechanical stimulation their apical hair bundles. We employed an vitro preparation intracellular recording investigate transduction mechanism cells sacculus from inner ear bullfrog (Rana catesbeiana). When stimulated directly by deflection bundles, these gave graded responses up 15 mV amplitude; peak sensitivity was about 20 mV/micron deflection. The...
The receptor current of hair cells from the bullfrog's sacculus was measured by voltage clamp recording across isolated sensory epithelium. Several hundred were stimulated en masse moving overlying otolithic membrane with a piezoelectrically activated probe. As optical motion, step displacement stimuli reached their final amplitudes up to 1 micrometer within 100 microseconds. relationship between and steady-state is an asymmetric, sigmoidal curve about 0.5 in extent. time constant approach...
To understand how cells differentially use the dozens of myosin isozymes present in each genome, we examined distribution four unconventional inner ear, a tissue that is particularly reliant on actin-rich structures and isozymes. Of isozymes, from different class, three are expressed hair amphibia mammals. In stereocilia, constructed cross-linked F-actin filaments, myosin-Iβ found mostly near stereociliary tips, myosin-VI largely absent, myosin-VIIa colocalizes with crosslinks connect...
We describe a novel mechanism for vital fluorescent dye entry into sensory cells and neurons: permeation through ion channels. In addition to the slow conventional uptake of styryl dyes by endocytosis, small such as FM1-43 rapidly specifically label hair in inner ear entering open mechanotransduction This labeling can be blocked pharmacological or mechanical closing phenomenon is not limited cell transduction channels, because human embryonic kidney 293T expressing vanilloid receptor (TRPV1)...
The vomeronasal organ (VNO) of terrestrial vertebrates plays a key role in the detection pheromones, chemicals released by animals that elicit stereotyped sexual and aggressive behaviors among conspecifics. Sensory transduction VNO appears unrelated to vertebrate olfactory visual systems: putative pheromone receptors are evolutionarily independent from odorant and, contrast transduction, is unlikely be mediated cyclic-nucleotide-gated channels. We hypothesized sensory might instead involve...
Myosin VIIa is a newly identified member of the myosin superfamily actin-based motors. Recently, gene was as defective in shaker-1, recessive deafness mice [Gibson, F., Walsh, J., Mburu, P., Varela, A., Brown, K.A., Antonio, M., Beisel, K.W., Steel, K.P. & S.D.M. (1995) Nature (London) 374, 62-64], and human Usher syndrome type 1B, an inherited disease characterized by congenital deafness, vestibular dysfunction, retinitis pigmentosa [Weil, D., Blanchard, S., Kaplan, Guilford, Gibson,...
Adaptation in a vestibular organ, the bullfrog's sacculus, was studied vivo and vitro. In experiments, discharge of primary saccular neurons extracellular response hair cells were recorded during steps linear acceleration. The responded at onset acceleration steps, then adapted fully within 10-50 msec. (microphonic) with similar time course, indicating that sources neural adaptation are peripheral to afferent synapse--in cell, its mechanical inputs, or both. Evidence for cell provided by 2...
Abstract Adeno-associated virus (AAV) vectors have shown promising results in preclinical models, but the genomic consequences of transduction with AAV encoding CRISPR-Cas nucleases is still being examined. In this study, we observe high levels integration (up to 47%) into Cas9-induced double-strand breaks (DSBs) therapeutically relevant genes cultured murine neurons, mouse brain, muscle and cochlea. Genome-wide mapping brain shows no overall increase except at CRISPR/Cas9 target site. To...
Transient receptor potential ankyrin 1 (TRPA1) is expressed by nociceptive neurons of the dorsal root ganglia (DRGs) and trigeminal ganglia, but its roles in cold mechanotransduction are controversial. To determine contribution TRPA1 to cutaneous primary afferent terminals, we used ex vivo skin–nerve preparation from Trpa1 +/+ , +/− −/− adult mouse littermates. Cutaneous fibers TRPA1-deficient mice showed no deficits acute sensitivity, they displayed striking mechanical response properties....
Hair cells of the inner ear are essential for hearing and balance. As a consequence, pathogenic variants in genes specifically expressed hair often cause hereditary deafness. few number not easily isolated from adjacent supporting cells, so biochemistry molecular biology can be difficult to study. To study gene expression we developed protocol cell isolation by FACS. With nearly pure surrounding cochlea utricle E16 P7, performed comprehensive type-specific RNA-Seq during mouse development....
Adeno-associated virus (AAV) is a safe and effective vector for gene therapy retinal disorders. Gene hearing disorders not as advanced, in part because delivery to sensory hair cells of the inner ear inefficient. Although AAV transduces mouse cochlea, outer remain refractory transduction. Here, we demonstrate that vector, exosome-associated (exo-AAV), potent carrier transgenes all cells. Exo-AAV1-GFP more efficient than conventional AAV1-GFP, both cochlear explants vitro with direct...