A5101968809- Hearing, Cochlea, Tinnitus, Genetics
- Hearing Loss and Rehabilitation
- Cancer-related molecular mechanisms research
- Nerve injury and regeneration
- Neuroscience and Neural Engineering
- Biochemical Analysis and Sensing Techniques
- Ear Surgery and Otitis Media
- Acoustic Wave Phenomena Research
- Plant Molecular Biology Research
- Marine animal studies overview
- Immune Response and Inflammation
- melanin and skin pigmentation
- Autism Spectrum Disorder Research
- Melanoma and MAPK Pathways
- NF-κB Signaling Pathways
- Single-cell and spatial transcriptomics
- Cystic Fibrosis Research Advances
- Antimicrobial Peptides and Activities
- bioluminescence and chemiluminescence research
- GaN-based semiconductor devices and materials
- Congenital heart defects research
- Ear and Head Tumors
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA regulation and disease
- Conducting polymers and applications
Stanford University
2015-2025
Jikei University School of Medicine
2023
Tokyo Medical Center
2023
Toho University
2023
Bionics Institute
2009-2022
The University of Melbourne
2009-2014
University of Iowa
2011
The degeneration of hair cells in the mammalian cochlea results permanent sensorineural hearing loss. This study aimed to promote regeneration sensory mature and their reconnection with auditory neurons through introduction ATOH1, a transcription factor known be necessary for cell development, neurotrophic factors. Adenoviral vectors containing ATOH1 alone, or neurotrophin-3 brain derived were injected into lower basal scala media guinea pig cochleae four days post ototoxic deafening. Guinea...
During development, Sox2 is indispensable for cell division and differentiation, yet its roles in regenerating tissues are less clear. Here, we used combinations of transgenic mouse models to reveal that haploinsufficiency (Sox2haplo) increases rather than impairs cochlear regeneration vivo. Sox2haplo cochleae had delayed terminal mitosis ectopic sensory cells, normal auditory function. amplified expanded domains damage-induced Atoh1+ transitional formation neonatal cochlea. Wnt activation...
Abstract Cochlear melanocytes are intermediate cells in the stria vascularis that generate endocochlear potentials required for auditory function. Human PAX3 mutations cause Waardenburg syndrome and abnormalities of skin retinal melanocytes, manifested as congenital hearing loss (~ 70%) hypopigmentation skin, hair eyes. However, underlying mechanism remains unclear. originated from Pax3 -traced melanoblasts Plp1 Schwann cell precursors, both which derive neural crest cells. Here, using a...
Abstract Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast the cochlea, vestibular cells of murine utricle have some regenerative capacity. Whether human utricular regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors schwannoma patients, present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers 13 sensory non-sensory types, with partial overlap correlation...
Significance Gentamicin is a potent aminoglycoside antibiotic with significant ototoxic side-effects. Although it administered as mixture of five main C-subtypes and <10% impurities, the significance unclear, partly because difficulty in chemically separating individual components. We established methods purifying gentamicin C-subtypes, found C2b to be least sisomicin most ototoxic, both antimicrobial comparable mixture. Ototoxicity varies among impurities highly correlates their affinity...
The cochlear implant provides auditory cues to profoundly deaf patients by electrically stimulating the residual spiral ganglion neurons. These neurons, however, undergo progressive degeneration after hearing loss, marked initially peripheral fibre retraction and ultimately culminating in cell death. This research aims use gene therapy techniques both hold reverse this providing a sustained localised source of neurotrophins deafened cochlea. Adenoviral vectors containing green fluorescent...
Modulator agents that restore cystic fibrosis transmembrane conductance regulator (CFTR) function have revolutionized outcomes in fibrosis, an incurable multisystem disease. Barriers exist to modulator use, making local CFTR gene and cell therapies attractive, especially the respiratory tract. We used CRISPR gene-correct upper airway basal stem cells (UABCs) show durable engraftment into recipient murine epithelium. Interestingly, human recapitulate vivo organization differentiation of sinus...
The hair bundle is the mechanosensory organelle of cells that detects mechanical stimuli caused by sounds, head motions, and fluid flows. Each an assembly cellular-protrusions called stereocilia, which differ in height to form a staircase. Stereocilia have different heights, widths, separations species, sensory organs, positions within organ, hair-cell types, even single bundle. dimensions stereociliary dictate how responds stimuli. These hair-bundle properties been measured previously only...
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,...
Gene therapy has been investigated as a way to introduce variety of genes treat neurological disorders. An important clinical consideration is its long-term effectiveness. This research aims study the expression and effectiveness gene in promoting spiral ganglion neuron survival after deafness. Adenoviral vectors modified express brain derived neurotrophic factor or neurotrophin-3 were unilaterally injected into guinea pig cochlea one week post ototoxic deafening. After six months,...
Cochlear supporting cells (SCs) are glia-like critical for hearing function. In the neonatal cochlea, greater epithelial ridge (GER) is a mitotically quiescent and transient organ, which has been shown to nonmitotically regenerate SCs. Here, we ablated Lgr5 + SCs using Lgr5-DTR mice found mitotic regeneration of by GER in vivo. With lineage tracing, show that houses progenitor robustly divide migrate into organ Corti replenish Regenerated display coordinated calcium transients, markers SC...
The mammalian cochlea contains three rows of outer hair cells (OHCs) that amplify the basilar membrane traveling wave with high gain and exquisite tuning. pattern OHC loss caused by typical methods producing hearing in animal models (noise, ototoxic exposure, or aging) is variable not consistent along length cochlea. Thus, it difficult to use these approaches understand how forces from multiple OHCs summate create normal cochlear amplification. Here, we selectively removed third row Deiters'...
Summary Recent advances in fate mapping and single-cell technologies have revealed how the dynamics function of tissue-resident macrophages are shaped by their environment. However, sensory organs such as cochlea where central nervous system peripheral meet remain understudied. Combining transcriptomics, mapping, parabiosis experiments, we show that five types myeloid cells including three macrophage subpopulations, coexist mouse cochlea. The subsets showed different potential functions...
Background: Degeneration of hair cells in the mammalian cochlea results irreversible hearing loss with no current treatment options to regain lost cell function. The Atoh1 gene is necessary for development and recent research has shown that therapy promotes new formation restoration adult rodent deafness models. Objective: aim this study was examine via noise-deafened guinea pigs. Methods: Guinea pigs were deafened by noise exposure (130 dB, 11-13 kHz, 2 hours). After two weeks, left...
Abstract Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast the cochlea, vestibular cells of murine utricle have some regenerative capacity. Whether human utricular regenerate remains unknown. Here we procured live, mature utricles from organ donors schwannoma patients, present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe previously unknown markers 25 sensory non-sensory types, with genes supporting...
The G protein-coupled receptor (GPR) family critically regulates development and homeostasis of multiple organs. As a member the GPR adhesion family, Gpr125 (Adgra3) modulates Wnt/PCP signaling convergent extension in developing zebrafish, but whether it is essential for cochlear mammals unknown. Here, we examined lacZ/+ knock-in mice show that dynamically expressed mature cochleae. From embryonic day (E) 15.5 to postnatal (P) 30, Gpr125-β-Gal consistently lesser epithelial ridge its...