A5100657071- Hearing, Cochlea, Tinnitus, Genetics
- Hearing Loss and Rehabilitation
- Acoustic Wave Phenomena Research
- Vestibular and auditory disorders
- Electron and X-Ray Spectroscopy Techniques
- Cancer-related molecular mechanisms research
- Photoreceptor and optogenetics research
- NF-κB Signaling Pathways
- Marine animal studies overview
- Noise Effects and Management
- Advanced Electron Microscopy Techniques and Applications
- Neuroscience and Neuropharmacology Research
- Biochemical Analysis and Sensing Techniques
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Response and Inflammation
- Neural dynamics and brain function
- Nerve injury and regeneration
- Congenital heart defects research
- Antimicrobial Peptides and Activities
- Ear Surgery and Otitis Media
- Ion channel regulation and function
- Developmental Biology and Gene Regulation
- Ion Channels and Receptors
- RNA Research and Splicing
- Semiconductor materials and devices
Guiyang Medical University
2025
Creighton University
1999-2024
St. Jude Children's Research Hospital
2011-2021
University of Illinois Urbana-Champaign
2001-2021
Norwegian University of Science and Technology
2021
Zhejiang University
2014
Fuda Cancer Hospital
2014
Jinan University
2014
Guangzhou Institutes of Biomedicine and Health
2014
University of Sussex
2011
Inner ear hair cells are specialized sensory essential for auditory function. Previous studies have shown that the epithelium is postmitotic, but it harbors can behave as progenitor in vitro, including ability to form new cells. Lgr5 , a Wnt target gene, marks distinct supporting cell types neonatal cochlea. Here, we tested hypothesis + Wnt-responsive precursor In contrast their quiescent vivo behavior, isolated by flow cytometry from EGFP-CreERT2/+ mice proliferated and formed clonal...
Loss of cochlear hair cells in mammals is currently believed to be permanent, resulting hearing impairment that affects more than 10% the population. Here, we developed two genetic strategies ablate neonatal mouse vivo. Both Pou4f3DTR/+ and Atoh1-CreER™; ROSA26DTA/+ alleles allowed selective inducible cell ablation. After loss was induced at birth, observed spontaneous regeneration cells. Fate-mapping experiments demonstrated neighboring supporting acquired a fate, which increased basal...
Unlike nonmammalian vertebrates, mammals cannot convert inner ear cochlear supporting cells (SCs) into sensory hair (HCs) after damage, thus causing permanent deafness. Here, we achieved in vivo conversion of two SC subtypes, pillar (PCs) and Deiters' (DCs), HCs by inducing targeted expression Atoh1 at neonatal juvenile ages using novel mouse models. The only occurred ∼10% PCs DCs with ectopic started reactivation endogenous followed 11 HC synaptic markers, a process that took approximately...
Chondroitin sulfate proteoglycans (CSPGs) are implicated in the regulation of axonal growth. We previously reported that neurite-promoting activity laminin is inhibited by association with a Schwann cell-derived CSPG and endoneurial may be this as well [Zuo J, Hernandez YJ, Muir D (1998) proteoglycan neurite-inhibiting upregulated after peripheral nerve injury. J Neurobiol 34:41-54]. Mechanisms regulating growth were studied using an vitro bioassay which regenerating embryonic dorsal root...
Recruitment of endogenous progenitors is critical during tissue repair. The inner ear utricle requires mechanosensory hair cells (HCs) to detect linear acceleration. After damage, non-mammalian utricles regenerate HCs via both proliferation and direct transdifferentiation. In adult mammals, limited transdifferentiation from unidentified occurs extrastriolar Type II HCs. Here we show that HC damage in neonatal mouse activates the Wnt target gene Lgr5 striolar supporting cells. Lineage tracing...
Highlights•Co-manipulation of ATOH1 and p27Kip1 creates new cochlear hair cells in adult mice•p27Kip1 noncanonically inhibits GATA3, an Atoh1 co-factor that promotes POU4F3•Ectopic POU4F3 upregulates cell markers supporting cochleae•ATOH1-based therapies may be improved by co-manipulation p27Kip1, or POU4F3SummaryHearing loss is widespread persistent because mature mammalian auditory (HCs) are nonregenerative. In mice, the ability to regenerate HCs from surrounding (SCs) declines abruptly...
The regeneration of mechanoreceptive hair cells occurs throughout life in non-mammalian vertebrates and allows them to recover from hearing balance deficits that affect humans other mammals permanently. irreversibility comparable remains unexplained, but often has been attributed steep embryonic declines cellular production. However, recent results suggest gravity-sensing murine utricles may increase number during neonatal development, raising the possibility young mice might retain...
The tonotopic map of the mammalian cochlea is commonly thought to be determined by passive mechanical properties basilar membrane. other tissues and cells that make up organ Corti also have properties; however, their roles are less well understood. In addition, active forces produced outer hair (OHCs) enhance vibration membrane, termed cochlear amplification. Here, we studied how these biomechanical components interact using optical coherence tomography, which permits vibratory measurements...
The mammalian cochlea exhibit minimal spontaneous regeneration, and loss of sensory hair cells (HCs) results in permanent hearing loss. In nonmammalian vertebrates, HC regeneration occurs through both proliferation differentiation surrounding supporting (SCs). postnatal cochleae vivo remains limited by the small number subsequent death regenerated HCs. Here, we describe generation 10-fold more new HCs mouse than previously reported, most which survive to adulthood. We achieved this combining...
Hearing loss caused by aging, noise, cisplatin toxicity, or other insults affects 360 million people worldwide, but there are no Food and Drug Administration-approved drugs to prevent treat it. We screened 4,385 small molecules in a cochlear cell line identified 10 compounds that protected against toxicity mouse explants. Among them, kenpaullone, an inhibitor of multiple kinases, including cyclin-dependent kinase 2 (CDK2), zebrafish lateral-line neuromasts from and, when delivered locally,...
Tumor infiltrating lymphocyte therapy (TIL therapy) is one of the effective treatments for solid tumors. However, certain periods or sites tumors are not amenable to surgical resection. Meanwhile, abundant and dense extracellular matrix (ECM) regulatory cells (e.g., T (Tregs), myeloid-derived suppressor (MDSC)) in when infused back into treatment will prevent cell infiltration proliferation, thus inhibiting efficacy this approach. In study, a novel preparation was successfully developed by...
Although the peripheral nerve has potential to regenerate after injury, degenerative processes may be essential promote axonal growth into denervated nerve. One hypothesis is that contains inhibitors must neutralized injury for optimal regeneration. In present study, we tested whether degradation of chondroitin sulfate proteoglycan, a known inhibitor axon growth, enhances growth-promoting properties grafts prepared from normal donor nerves. Excised segments rat sciatic were made acellular by...
Gross-potential recordings in mice lacking the Prestin gene indicate that compound action potential (CAP) thresholds are shifted by approximately 45 dB at 5 kHz and 60 33 kHz. However, order to conclude outer hair cell (OHC) electromotility is associated with cochlear amplifier, frequency selectivity must be evaluated integrity of OHC's forward transducer ascertained. The present report demonstrates no CAP tuning curves recorded homozygotes. In addition, input-output functions responses...
Regeneration of auditory hair cells (HCs) is a promising approach to restore hearing. Recent studies have demonstrated that induced pluripotent stem cells/embryonic or supporting (SCs) adjacent HCs can be converted adopt the HC fate. However, little known about whether new are characteristic outer inner HCs. Here, we showed in vivo conversion 2 subtypes SCs, border (IBs) and phalangeal (IPhs), (IHC) This was achieved by ectopically activating Atoh1, transcription factor necessary for fate,...
Abstract Disordered proteins are highly prevalent in biological systems, they control myriad signaling and regulatory processes their levels and/or cellular localization often altered human disease. In contrast to folded proteins, disordered due conformational heterogeneity dynamics, not considered viable drug targets. We challenged this paradigm by identifying through NMR-based screening small molecules that bound specifically, albeit weakly, the cell cycle regulator, p27 Kip1 (p27). Two...
In vivo direct conversion of differentiated cells holds promise for regenerative medicine; however, improving the efficiency and producing functional target remain challenging. Ectopic Atoh1 expression in non-sensory supporting (SCs) mouse cochleae induces their partial to hair (HCs) at low efficiency. Here, we performed single-cell RNA sequencing whole sensory epithelia harvested multiple time points after conditional overexpression Atoh1. Pseudotemporal ordering revealed that converted HCs...