Lei Song, MD, PhD
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Featured Publications
Differential outcomes of high‐fat diet on age‐related rescaling of cochlear frequency place coding
Zhang Y, Lin G, Xue N, Wang Y, Du T, Liu H, Xiong W, Shang W, Wu H, Song L. Differential outcomes of high‐fat diet on age‐related rescaling of cochlear frequency place coding. The FASEB Journal 2023, 37: e23167. PMID: 37651093, DOI: 10.1096/fj.202300457rr.Peer-Reviewed Original ResearchConceptsAge-related hearing lossHigh-fat dietHearing lossEffects of HFDLoss of OHCsActivation of TRPV1Sensorineural hearing lossCBA/CaJPlace codingCochlear frequency selectivityTRPV1 expressionOHC functionInflammatory responseCommon causeHFD cohortGenetic backgroundYounger ageArachidonic acidCochlear lengthHair cellsPrestin levelsLipid homeostasisRescuing effectCochlear amplificationAgePrestin derived OHC surface area reduction underlies age‐related rescaling of frequency place coding
Zhang Y, Lin G, Wang Y, Xue N, Lin X, Du T, Xiong W, Song L. Prestin derived OHC surface area reduction underlies age‐related rescaling of frequency place coding. Hearing Research 2021, 423: 108406. PMID: 34933788, DOI: 10.1016/j.heares.2021.108406.Peer-Reviewed Original Research
2025
Casz1 is required for both inner hair cell fate stabilization and outer hair cell survival
Sun Y, Ren M, Zhang Y, Li S, Luo Z, Sun S, He S, Wang G, Zhang D, Mansour S, Song L, Liu Z. Casz1 is required for both inner hair cell fate stabilization and outer hair cell survival. Science 2025, eado4930. PMID: 39883789, DOI: 10.1126/science.ado4930.Peer-Reviewed Original ResearchCell fate stabilityLoss of Casz1Transcription factor CASZ1Outer hair cell survivalCochlear inner hair cellsTranscription factor GATA3Transcription factorsCASZ1Mouse developmentCell survivalHair cell survivalInner hair cellsOuter hair cell numberTranscriptionDown-regulationHair cellsOverexpressing GATA3Mutant miceOuter hair cellsCellsOHC survivalGATA3Mice
2024
The p. S178L mutation in Tbc1d24 disrupts endosome‐mediated synaptic vesicle trafficking of cochlear hair cells and leads to hearing impairment in mice
Chen P, Hou S, Li G, Lin Y, Lu J, Song L, Li G, Pang X, Wu H, Yang T. The p. S178L mutation in Tbc1d24 disrupts endosome‐mediated synaptic vesicle trafficking of cochlear hair cells and leads to hearing impairment in mice. Clinical Genetics 2024, 107: 67-77. PMID: 39400345, DOI: 10.1111/cge.14620.Peer-Reviewed Original ResearchNon-syndromic hearing lossSynaptic vesiclesRibbon synapses of cochlear inner hair cellsAutosomal dominant non-syndromic hearing lossDominant non-syndromic hearing lossEndosome-like vacuolesEndosomal membrane traffickingInner hair cellsSynaptic vesicle traffickingHearing lossRibbon synapsesHair cell ribbon synapsesKnock-in mouse modelMutant miceSustained exocytosisVesicle traffickingEndosomal traffickingMembrane traffickingVesicle recyclingIn vitro interactionCochlear inner hair cellsReduced exocytosisWave I amplitudeMild hearing lossAuditory brainstem responseDMXL2 Is Required for Endocytosis and Recycling of Synaptic Vesicles in Auditory Hair Cells
Peng H, Wang L, Gao Y, Liu H, Lin G, Kong Y, Xu P, Liu H, Yuan Q, Liu H, Song L, Yang T, Wu H. DMXL2 Is Required for Endocytosis and Recycling of Synaptic Vesicles in Auditory Hair Cells. Journal Of Neuroscience 2024, 44: e1405232024. PMID: 39147590, PMCID: PMC11411588, DOI: 10.1523/jneurosci.1405-23.2024.Peer-Reviewed Original ResearchEndocytic membrane retrievalSynaptic vesiclesSynaptic exocytosisMembrane retrievalEndocytic compartmentsMolecular machineryRecycling of synaptic vesiclesReserve poolMembrane capacitance measurementsRibbon synapses of inner hair cellsElectron microscopy reconstructionsAuditory synaptopathyMutant miceSynaptic endocytosisCell-specific knockout miceHuman homologMembrane-proximalHair cellsAuditory hair cellsMolecular basisEndocytosisRibbon synapsesInner hair cellsHearing lossDMXL2Revisiting the Potency of Tbx2 Expression in Transforming Outer Hair Cells into Inner Hair Cells at Multiple Ages In Vivo
Bi Z, Ren M, Zhang Y, He S, Song L, Li X, Liu Z. Revisiting the Potency of Tbx2 Expression in Transforming Outer Hair Cells into Inner Hair Cells at Multiple Ages In Vivo. Journal Of Neuroscience 2024, 44: e1751232024. PMID: 38688721, PMCID: PMC11154855, DOI: 10.1523/jneurosci.1751-23.2024.Peer-Reviewed Original Research
2023
In situ regeneration of inner hair cells in the damaged cochlea by temporally regulated co-expression of Atoh1 and Tbx2
Li X, Ren M, Gu Y, Zhu T, Zhang Y, Li J, Li C, Wang G, Song L, Bi Z, Liu Z. In situ regeneration of inner hair cells in the damaged cochlea by temporally regulated co-expression of Atoh1 and Tbx2. Development 2023, 150 PMID: 38078650, DOI: 10.1242/dev.201888.Peer-Reviewed Original ResearchDifferential regulation of hair cell actin cytoskeleton mediated by SRF and MRTFB
Zhou L, Jin C, Wang W, Song L, Shin J, Du T, Wu H. Differential regulation of hair cell actin cytoskeleton mediated by SRF and MRTFB. ELife 2023, 12: e90155. PMID: 37982489, PMCID: PMC10703445, DOI: 10.7554/elife.90155.Peer-Reviewed Original ResearchConceptsActin cytoskeletonRegulation of actin cytoskeletonMRTF-SRF pathwayModulating actin dynamicsCell actin cytoskeletonCuticular plateActin cytoskeleton organizationActin cytoskeleton activityTranscriptional regulation mechanismRNA-seq analysisF-actin intensityHair cell developmentProfiles of genesActin dynamicsCytoskeleton organizationTranscriptional regulationF-actinCalponin 2Cytoskeleton activityHair bundle morphologyTranscriptome analysisDifferential regulationCell developmentCell-specific deletionCytoskeletonCochlear transcript diversity and its role in auditory functions implied by an otoferlin short isoform
Liu H, Liu H, Wang L, Song L, Jiang G, Lu Q, Yang T, Peng H, Cai R, Zhao X, Zhao T, Wu H. Cochlear transcript diversity and its role in auditory functions implied by an otoferlin short isoform. Nature Communications 2023, 14: 3085. PMID: 37248244, PMCID: PMC10227054, DOI: 10.1038/s41467-023-38621-3.Peer-Reviewed Original ResearchConceptsShort isoformEndocytic membrane retrievalRNA sequencing techniquesDiverse biological functionsInner hair cellsTranscript diversityUnannotated transcriptsRNA-seqAlternative isoformsMembrane retrievalBiological functionsGENCODE databasesKey proteinsIsoform resolutionSequencing techniquesSustained exocytosisIsoformsMechanistic understandingAuditory functionSanger sequencingHair cellsTranscriptsRT-PCRSynaptic transmissionAuditory phenotypeRole of mitochondrial dysfunction and oxidative stress in sensorineural hearing loss
Tan W, Song L. Role of mitochondrial dysfunction and oxidative stress in sensorineural hearing loss. Hearing Research 2023, 434: 108783. PMID: 37167889, DOI: 10.1016/j.heares.2023.108783.Peer-Reviewed Original ResearchConceptsSensorineural hearing lossOtotoxic drugsMitochondrial dysfunctionReactive oxygen speciesOxidative stressHearing lossDevelopment of SNHLMitochondrial reactive oxygen speciesSpiral ganglion neuronsMitochondrial DNA mutationsPrecise pathophysiological mechanismsSensory hair cellsHair cell mitochondriaConsequent oxidative stressCentral etiological roleMtDNA mutationsPathophysiological mechanismsGanglion neuronsAntioxidant therapyCalcium dysregulationDNA mutationsCell mitochondriaClinical studiesCochlear cellsEtiological role
News
News
- February 15, 2012
Yale study: how mitochondrial DNA defects cause inherited deafness
- December 01, 2008
Grants and contracts awarded to Yale School of Medicine
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