A5011210102- Hearing, Cochlea, Tinnitus, Genetics
- Hearing Loss and Rehabilitation
- Vestibular and auditory disorders
- Acoustic Wave Phenomena Research
- Cancer-related molecular mechanisms research
- Animal Vocal Communication and Behavior
- Ion Channels and Receptors
- Ear Surgery and Otitis Media
- Marine animal studies overview
- Neuroscience of respiration and sleep
- Immune Cell Function and Interaction
- Developmental Biology and Gene Regulation
- Cardiac Ischemia and Reperfusion
- Biochemical Analysis and Sensing Techniques
- Congenital heart defects research
- Neuroscience and Neuropharmacology Research
- Protein Kinase Regulation and GTPase Signaling
- Anesthesia and Neurotoxicity Research
- Single-cell and spatial transcriptomics
- Receptor Mechanisms and Signaling
- Calcium signaling and nucleotide metabolism
- MicroRNA in disease regulation
- Synthesis of Organic Compounds
- Nicotinic Acetylcholine Receptors Study
- Connexins and lens biology
Creighton University
2016-2025
University College London
2013-2023
First Affiliated Hospital of Zhengzhou University
2023
Cardiovascular Institute of the South
2013-2022
Institute of Pharmacology
2020
Academy of Military Medical Sciences
2020
Chongqing Medical University
2019
Children's Hospital of Chongqing Medical University
2019
Ningbo University
2013-2014
Boys Town National Research Hospital
2001-2003
Outer hair cells (OHCs) of the mammalian cochlea actively change their cell length in response to changes membrane potential. This electromotility, thought be basis cochlear amplification, is mediated by a voltage-sensitive motor molecule recently identified as protein prestin. Here, we show that voltage sensitivity conferred prestin intracellular anions chloride and bicarbonate. Removal these abolished fast voltage-dependent motility, well characteristic nonlinear charge movement (“gating...
The dominant efferent innervation of the cochlea terminates on outer hair cells (OHCs), with acetylcholine (ACh) being its principal neurotransmitter. OHCs respond a somatic shape change to alterations in their membrane potential, and this electromotile response is believed provide mechanical feedback basilar membrane. We examine effects ACh responses isolated attempt deduce mechanism action. Axial amplitude cell compliance increase presence ligand. This occurs significantly greater latency...
Inner hair cells (IHCs) and outer (OHCs) are the two types of sensory receptor that critical for hearing in mammalian cochlea. IHCs OHCs have different morphology function. The genetic mechanisms define their morphological functional specializations essentially unknown. transcriptome reflects genes being actively expressed a cell holds key to understanding molecular biological properties cell. Using DNA microarray, we examined 2000 individually collected from adult mouse cochleae. We show...
Single-cell RNA sequencing is a powerful tool by which to characterize the transcriptional profile of low-abundance cell types, but its application inner ear has been hampered bony labyrinth, tissue sparsity, and difficulty dissociating ultra-rare cells membranous cochlea. Herein, we present method isolate individual hair (IHCs), outer (OHCs), Deiters' (DCs) from murine cochlea at any post-natal time point. We harvested more than 200 IHCs, OHCs, DCs days 15 (p15) 228 (p228) leveraged both...
The mammalian auditory sensory epithelium, the organ of Corti, is composed hair cells and supporting cells. Hair contain specializations in apical, basolateral synaptic membranes. These mediate mechanotransduction, electrical mechanical activities transmission. Supporting maintain homeostasis ionic chemical environment cochlea contribute to stiffness cochlear partition. While spontaneous proliferation transdifferentiation are source regenerative response replace lost lower vertebrates, adult...
Age-related hearing loss (ARHL) negatively impacts quality of life in the elderly population. The prevalent cause ARHL is mechanosensitive cochlear hair cells (HCs). molecular and cellular mechanisms HC degeneration remain poorly understood. Using RNA-seq transcriptomic analyses inner outer HCs isolated from young aged mice, we show that aging associated with changes key processes, including transcription, DNA damage, autophagy, oxidative stress, as well genes related to specialization. At...
The hallmark of mechanosensory hair cells is the stereocilia, where mechanical stimuli are converted into electrical signals. These delicate stereocilia susceptible to acoustic trauma and ototoxic drugs. While in lower vertebrates mammalian vestibular system can spontaneously regenerate lost cochlear no longer retain this capability. We explored possibility regenerating noise-deafened guinea pig cochlea by inoculation a viral vector carrying Atoh1, gene critical for cell differentiation....
MicroRNAs (miRNAs), a class of short non-coding RNAs that regulate the expression mRNA targets, are important regulators cellular senescence and aging. We questioned which miRNAs involved in age-related degeneration organ Corti (OC), auditory sensory epithelium transduces mechanical stimuli to electrical activity inner ear. Degeneration OC is generally accepted as main cause hearing loss (ARHL), progressive individuals they grow older. To determine onset progression ARHL, miRNA gene two...
Abstract Inner hair cells (IHCs) and outer (OHCs) are the two anatomically functionally distinct types of mechanosensitive receptor in mammalian cochlea. The molecular mechanisms defining their morphological functional specializations largely unclear. As a first step to uncover underlying mechanisms, we examined transcriptomes IHCs OHCs isolated from adult CBA/J mouse cochleae. One thousand were separately collected using suction pipette technique. RNA sequencing was performed analyzed....
Cochlear hair cells and the stria vascularis are critical for normal hearing. Hair transduce mechanical stimuli into electrical signals, whereas is responsible generating endocochlear potential (EP), which driving force cell mechanotransduction. We questioned whether interdepend survival by using two mouse models. Atoh1 conditional knockout mice, lose all within four weeks after birth, were used to determine absence of would affect function stria. showed that morphology EP remained long time...
Abstract Age-related vestibular dysfunction (ARVD) is a prevalent, debilitating condition in the elderly. The etiology and molecular mechanisms are poorly understood. We focused on mechanosensitive hair cells (HCs) as they particularly vulnerable to aging. Using single-cell RNA-seq transcriptomes of young old mouse HCs, we show that aging HCs display both universal blueprints, such genomic instability, mitochondrial dysfunction, impaired proteostasis, cell type-specific signatures associated...
The mammalian cochlea depends on an amplification process for its sensitivity and frequency-resolving capability. Outer hair cells are responsible providing this amplification. It is usually assumed that the membrane-potential-driven somatic shape changes of these basis amplifying process. interest to see whether mechanical reactance might accompany their in cell shape. We now show cylindrical outer change axial stiffness as membrane potential altered. Cell was determined by...
Background Mutations in SLC26A4, which encodes pendrin, are a common cause of deafness. SLC26A4 mutations responsible for Pendred syndrome and non-syndromic enlarged vestibular aqueduct (EVA). The mutation spectrum varies widely among ethnic groups. To investigate the incidence EVA Chinese population to provide appropriate genetic testing counseling patients with variants, we conducted large-scale molecular epidemiological survey SLC26A4. Methods A total 2352 unrelated hearing loss from 27...
Hearing loss caused by noise, aging, antibiotics, and chemotherapy affects 10% of the world population, yet there are no Food Drug Administration (FDA)-approved drugs to prevent it. Here, we screened 162 small-molecule kinase-specific inhibitors for reduction cisplatin toxicity in an inner ear cell line identified dabrafenib (TAFINLAR), a BRAF kinase inhibitor FDA-approved cancer treatment. Dabrafenib six additional BRAF/MEK/ERK cellular pathway mitigated cisplatin-induced hair death mouse...
Juvenile and mature mouse cochleae contain various low-abundant, vulnerable sensory epithelial cells embedded in the calcified temporal bone, making it challenging to profile dynamic transcriptome changes of these during maturation at single-cell level. Here we performed 10x Genomics RNA sequencing (scRNA-seq) postnatal days 14 (P14) 28. We attained transcriptomes multiple cell types, including hair cells, supporting spiral ganglia, stria fibrocytes, immune cells. Our scRNA-seq datasets are...