2024
Nav1.8 in small dorsal root ganglion neurons contributes to vincristine-induced mechanical allodynia
Nascimento de Lima A, Zhang H, Chen L, Effraim P, Gomis-Perez C, Cheng X, Huang J, Waxman S, Dib-Hajj S. Nav1.8 in small dorsal root ganglion neurons contributes to vincristine-induced mechanical allodynia. Brain 2024, 147: 3157-3170. PMID: 38447953, DOI: 10.1093/brain/awae071.Peer-Reviewed Original ResearchDorsal root ganglion neuronsDorsal root ganglionVincristine-induced mechanical allodyniaVincristine-induced peripheral neuropathyMechanical allodyniaVincristine treatmentNav1.8 channelsSmall dorsal root ganglion neuronsDevelopment of mechanical allodyniaTTX-R current densityVoltage-gated sodium channel Nav1.6Vincristine-treated animalsCurrent-clamp recordingsSodium channel Nav1.8Voltage-clamp recordingsReducing current thresholdSodium channel Nav1.6Investigate pathophysiological mechanismsTTX-RHyperpolarizing shiftRoot ganglionAllodyniaGanglion neuronsVincristine administrationPeripheral neuropathyTRPM8 mutations associated with persistent ocular pain after refractive surgery: D665N and V915M
Ghovanloo M, Effraim P, Tyagi S, Cheng X, Yuan J, Schulman B, Jacobs D, Dib-Hajj S, Waxman S. TRPM8 mutations associated with persistent ocular pain after refractive surgery: D665N and V915M. Biophysical Journal 2024, 123: 391a. DOI: 10.1016/j.bpj.2023.11.2376.Peer-Reviewed Original Research
2023
Genetic, electrophysiological, and pathological studies on patients with SCN9A‐related pain disorders
Yuan J, Cheng X, Matsuura E, Higuchi Y, Ando M, Hashiguchi A, Yoshimura A, Nakachi R, Mine J, Taketani T, Maeda K, Kawakami S, Kira R, Tanaka S, Kanai K, Dib‐Hajj F, Dib‐Hajj S, Waxman S, Takashima H. Genetic, electrophysiological, and pathological studies on patients with SCN9A‐related pain disorders. Journal Of The Peripheral Nervous System 2023, 28: 597-607. PMID: 37555797, DOI: 10.1111/jns.12590.Peer-Reviewed Original ResearchConceptsParoxysmal extreme pain disorderPainful peripheral neuropathyPain disordersSCN9A mutationsPeripheral neuropathyNovel SCN9A mutationsVoltage-gated sodium channel Nav1.7Sodium channel Nav1.7Steady-state fast inactivationGene panel sequencingPatch-clamp analysisAutonomic neuropathyNeuropathic painSCN9A geneClinical featuresUnderlying pathogenesisPathological studiesPatientsChannel Nav1.7EM phenotypePhenotypic spectrumNeuropathyNav1.7 channelsPatch-clamp systemElectrophysiological analysisPain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function
Jami S, Deuis J, Klasfauseweh T, Cheng X, Kurdyukov S, Chung F, Okorokov A, Li S, Zhang J, Cristofori-Armstrong B, Israel M, Ju R, Robinson S, Zhao P, Ragnarsson L, Andersson Å, Tran P, Schendel V, McMahon K, Tran H, Chin Y, Zhu Y, Liu J, Crawford T, Purushothamvasan S, Habib A, Andersson D, Rash L, Wood J, Zhao J, Stehbens S, Mobli M, Leffler A, Jiang D, Cox J, Waxman S, Dib-Hajj S, Neely G, Durek T, Vetter I. Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function. Nature Communications 2023, 14: 2442. PMID: 37117223, PMCID: PMC10147923, DOI: 10.1038/s41467-023-37963-2.Peer-Reviewed Original ResearchConceptsSensory neuronsVoltage-sensing domainNav channelsTransmembrane proteinAccessory proteinsVoltage-gated sodium channelsCritical regulatorPore domainChannel gatingExtracellular loopToxin-mediated effectsNeuronal excitabilityPeptide toxinsProteinSodium channelsPharmacological activitiesNav1.7 functionKnottin peptidesNeuronsImportant insightsToxinSubunitsRegulatorDomainExcelsaKv7-specific activators hyperpolarize resting membrane potential and modulate human iPSC-derived sensory neuron excitability
Estacion M, Liu S, Cheng X, Dib-Hajj S, Waxman S. Kv7-specific activators hyperpolarize resting membrane potential and modulate human iPSC-derived sensory neuron excitability. Frontiers In Pharmacology 2023, 14: 1138556. PMID: 36923357, PMCID: PMC10008904, DOI: 10.3389/fphar.2023.1138556.Peer-Reviewed Original Research
2019
Altered allostery of the left flipper domain underlies the weak ATP response of rat P2X5 receptors
Sun L, Liu Y, Wang J, Huang L, Yang Y, Cheng X, Fan Y, Zhu M, Liang H, Tian Y, Wang H, Guo C, Yu Y. Altered allostery of the left flipper domain underlies the weak ATP response of rat P2X5 receptors. Journal Of Biological Chemistry 2019, 294: 19589-19603. PMID: 31727741, PMCID: PMC6926468, DOI: 10.1074/jbc.ra119.009959.Peer-Reviewed Original ResearchConceptsFuture transgenic studiesFull-length variantATP responseTransmembrane domainTransgenic studiesMammalian speciesP2X5 receptorsAllosteryPathological functionsSingle replacementSingle-channel recordingsSkeletal muscleExon 10Molecular modelingFunctional subtypesATPResiduesNervous systemP2X5ReceptorsDomainMammalsSpeciesTM2Lack of knowledge
2018
Molecular mechanism underlying the subtype-selectivity of competitive inhibitor NF110 and its distinct potencies in human and rat P2X3 receptors
Li B, Wang J, Cheng X, Liu Y, Yang Y, Yang X, Guo C, Niu Y, Cao P, Lu X, Zhu M, Tian Y, Yu Y. Molecular mechanism underlying the subtype-selectivity of competitive inhibitor NF110 and its distinct potencies in human and rat P2X3 receptors. Science Bulletin 2018, 63: 1616-1625. PMID: 36658853, DOI: 10.1016/j.scib.2018.11.016.Peer-Reviewed Original ResearchP2X3 receptorsP2X receptorsExperimental animalsDifferent P2X receptorsLower bodyRat P2X3 receptorsDistinct potenciesSubtype-selective mannerHuman P2X3 receptorsLF domainInhibitors/modulatorsPreclinical dataClinical trialsAmino acidsEquivalent amino acidsATP-binding pocketClinical researchExtracellular ATPSubstitution of residuesReceptorsCation channelsPharmacological activitiesDorsal fin domainInhibitory efficacyChannel activityDruggable negative allosteric site of P2X3 receptors
Wang J, Wang Y, Cui W, Huang Y, Yang Y, Liu Y, Zhao W, Cheng X, Sun W, Cao P, Zhu M, Wang R, Hattori M, Yu Y. Druggable negative allosteric site of P2X3 receptors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: 4939-4944. PMID: 29674445, PMCID: PMC5948998, DOI: 10.1073/pnas.1800907115.Peer-Reviewed Original ResearchConceptsAllosteric siteNegative allosteric siteDruggable allosteric sitesG protein-coupled receptorsAllosteric modulationLeft flipperProtein-coupled receptorsNew drug targetsDorsal fin domainLB domainsClinical trialsP2X receptorsAllosteric changesAllosteric inhibitorsChannel mutantsDrug targetsPhase II clinical trialFunctional studiesFin domainRefractory chronic coughIdiopathic pulmonary fibrosisIon channelsLower bodyX-ray crystallographyNegative allosteric modulationGain of Function NaV1.7 Mutations in Idiopathic Small Fiber Neuropathy
Faber C, Hoeijmakers J, Ahn H, Cheng X, Han C, Choi J, Estacion M, Lauria G, Vanhoutte E, Gerrits M, Dib-Hajj S, Drenth J, Waxman S, Merkies I. Gain of Function NaV1.7 Mutations in Idiopathic Small Fiber Neuropathy. 2018, 175-194. DOI: 10.7551/mitpress/10310.003.0022.Peer-Reviewed Original ResearchNav1.7 is phosphorylated by Fyn tyrosine kinase which modulates channel expression and gating in a cell type-dependent manner
Li Y, Zhu T, Yang H, Dib-Hajj S, Waxman S, Yu Y, Xu TL, Cheng X. Nav1.7 is phosphorylated by Fyn tyrosine kinase which modulates channel expression and gating in a cell type-dependent manner. Molecular Pain 2018, 14: 1744806918782229. PMID: 29790812, PMCID: PMC6024516, DOI: 10.1177/1744806918782229.Peer-Reviewed Original ResearchConceptsND7/23 cellsDRG neuron excitabilityModulation of Nav1.7New pain therapeuticsVoltage-gated sodium channel Nav1.7Fyn kinaseWhole-cell recordingsSodium channel Nav1.7Elevated protein expressionCell type-specific modulationHuman embryonic kidney 293 cellsTyrosine kinasePain disordersEmbryonic kidney 293 cellsPain therapeuticsNeuron excitabilityPain perceptionMutant channelsChannel Nav1.7Kidney 293 cellsNav1.7HEK-293 cellsNav1.7 channelsCell type-dependent mannerType-dependent manner
2017
The nonproton ligand of acid-sensing ion channel 3 activates mollusk-specific FaNaC channels via a mechanism independent of the native FMRFamide peptide
Yang X, Niu Y, Liu Y, Yang Y, Wang J, Cheng X, Liang H, Wang H, Hu Y, Lu X, Zhu M, Xu T, Tian Y, Yu Y. The nonproton ligand of acid-sensing ion channel 3 activates mollusk-specific FaNaC channels via a mechanism independent of the native FMRFamide peptide. Journal Of Biological Chemistry 2017, 292: 21662-21675. PMID: 29123030, PMCID: PMC5766947, DOI: 10.1074/jbc.m117.814707.Peer-Reviewed Original ResearchConceptsDEG/ENaCDegenerin/epithelial sodium channelIon channelsAcid-sensing ion channelsMammalian acid-sensing ion channelsSodium channelsDiverse functionsKey residuesEpithelial sodium channelFMRFamide peptidesAncient featureChannel gatingActivation mechanismDistinct mechanismsSubfamiliesMammalsENaCUnitary conductancePathological processesNew insightsNonproton ligandIon selectivityEndogenous agonistSynaptic transmissionFaNaCN1366S mutation of human skeletal muscle sodium channel causes paramyotonia congenita
Ke Q, Ye J, Tang S, Wang J, Luo B, Ji F, Zhang X, Yu Y, Cheng X, Li Y. N1366S mutation of human skeletal muscle sodium channel causes paramyotonia congenita. The Journal Of Physiology 2017, 595: 6837-6850. PMID: 28940424, PMCID: PMC5685822, DOI: 10.1113/jp274877.Peer-Reviewed Original ResearchIntersubunit physical couplings fostered by the left flipper domain facilitate channel opening of P2X4 receptors
Wang J, Sun L, Cui W, Zhao W, Ma X, Li B, Liu Y, Yang Y, Hu Y, Huang L, Cheng X, Li L, Lu X, Tian Y, Yu Y. Intersubunit physical couplings fostered by the left flipper domain facilitate channel opening of P2X4 receptors. Journal Of Biological Chemistry 2017, 292: 7619-7635. PMID: 28302727, PMCID: PMC5418059, DOI: 10.1074/jbc.m116.771121.Peer-Reviewed Original ResearchFGF13 Selectively Regulates Heat Nociception by Interacting with Nav1.7
Yang L, Dong F, Yang Q, Yang P, Wu R, Wu Q, Wu D, Li C, Zhong Y, Lu Y, Cheng X, Xu F, Chen L, Bao L, Zhang X. FGF13 Selectively Regulates Heat Nociception by Interacting with Nav1.7. Neuron 2017, 93: 806-821.e9. PMID: 28162808, DOI: 10.1016/j.neuron.2017.01.009.Peer-Reviewed Original ResearchConceptsDorsal root gangliaAction potential firingHeat nociceptionFibroblast growth factorDRG neuronsSustained action potential firingTransient receptor potential cation channel V1Intracellular fibroblast growth factorsNoxious heat stimulationNoxious heat stimuliMouse DRG neuronsNociceptive neuronsNociceptive behaviorSodium channel NaRoot gangliaHeat stimuliNociceptionAction potentialsSodium currentHeat stimulationGrowth factorFGF13NeuronsChannel NaCurrent knowledge
2016
Long noncoding RNA glypican 3 (GPC3) antisense transcript 1 promotes hepatocellular carcinoma progression via epigenetically activating GPC3
Zhu X, Yuan J, Zhu T, Li Y, Cheng X. Long noncoding RNA glypican 3 (GPC3) antisense transcript 1 promotes hepatocellular carcinoma progression via epigenetically activating GPC3. The FEBS Journal 2016, 283: 3739-3754. PMID: 27573079, DOI: 10.1111/febs.13839.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAlpha-FetoproteinsAnimalsBiomarkers, TumorCarcinoma, HepatocellularCell Line, TumorDisease ProgressionEpigenesis, GeneticGlypicansHep G2 CellsHeterograftsHistonesHumansLiver NeoplasmsMiceMice, NudePrognosisPromoter Regions, GeneticRNA, AntisenseRNA, Long NoncodingTranscriptional ActivationUp-RegulationConceptsHCC cell proliferationBarcelona Clinic Liver Cancer stageCell proliferationTranscript 1Inhibited HCC cell proliferationLiver Cancer stageHepatocellular carcinoma screeningPotential therapeutic targetXenograft tumor growthHepatocellular carcinoma progressionP300/CBP-associated factorWorse prognosisCarcinoma screeningMicrovascular invasionTumor sizeHCC patientsCancer stageTherapeutic targetHCC progressionTumor growthCarcinoma progressionPotential biomarkersPathophysiological processesHCC tissuesSignificant upregulationExploration of the Peptide Recognition of an Amiloride-sensitive FMRFamide Peptide-gated Sodium Channel*
Niu Y, Yang Y, Liu Y, Huang L, Yang X, Fan Y, Cheng X, Cao P, Hu Y, Li L, Lu X, Tian Y, Yu Y. Exploration of the Peptide Recognition of an Amiloride-sensitive FMRFamide Peptide-gated Sodium Channel*. Journal Of Biological Chemistry 2016, 291: 7571-7582. PMID: 26867576, PMCID: PMC4817185, DOI: 10.1074/jbc.m115.710251.Peer-Reviewed Original ResearchA Highly Conserved Salt Bridge Stabilizes the Kinked Conformation of β2,3-Sheet Essential for Channel Function of P2X4 Receptors*
Zhao W, Sun M, Sun L, Liu Y, Yang Y, Huang L, Fan Y, Cheng X, Cao P, Hu Y, Li L, Tian Y, Wang R, Yu Y. A Highly Conserved Salt Bridge Stabilizes the Kinked Conformation of β2,3-Sheet Essential for Channel Function of P2X4 Receptors*. Journal Of Biological Chemistry 2016, 291: 7990-8003. PMID: 26865631, PMCID: PMC4825005, DOI: 10.1074/jbc.m115.711127.Peer-Reviewed Original Research
2015
ASIC3 Mediates Itch Sensation in Response to Coincident Stimulation by Acid and Nonproton Ligand
Peng Z, Li W, Huang C, Jiang Y, Wang X, Zhu M, Cheng X, Xu T. ASIC3 Mediates Itch Sensation in Response to Coincident Stimulation by Acid and Nonproton Ligand. Cell Reports 2015, 13: 387-398. PMID: 26440887, DOI: 10.1016/j.celrep.2015.09.002.Peer-Reviewed Original ResearchConceptsAcid-sensing ion channel 3Itch sensationPrimary sensory neuronsIon channel 3ASIC3 geneSL-NH2Concomitant inflammationScratching behaviorPathological changesCoincident stimulationTissue acidosisASIC3 channelsSensory neuronsAcidosisNonproton ligandPruritogensSensationIle-GlyChannel 3Arg-LeuInflammationItchMiceNeuronsDesensitizationCytotoxic T cell responses are enhanced by antigen design involving the presentation of MUC1 peptide on cholera toxin B subunit
Lu W, Qiu L, Yan Z, Lin Z, Cao M, Hu C, Wang Z, Wang J, Yu Y, Cheng X, Cao P, Li R. Cytotoxic T cell responses are enhanced by antigen design involving the presentation of MUC1 peptide on cholera toxin B subunit. Oncotarget 2015, 6: 34537-34548. PMID: 26417929, PMCID: PMC4741471, DOI: 10.18632/oncotarget.5307.Peer-Reviewed Original ResearchMeSH KeywordsAdjuvants, ImmunologicAnimalsAntigen PresentationBlotting, WesternCancer VaccinesCholera ToxinDisease Models, AnimalEpitopes, B-LymphocyteFemaleFluorescent Antibody TechniqueLymphocyte ActivationMiceMice, Inbred C57BLMinisatellite RepeatsMucin-1Polymerase Chain ReactionT-Lymphocytes, CytotoxicVaccines, SubunitConceptsCytotoxic T lymphocytesMUC1-specific cytotoxic T lymphocytesElicit cytotoxic T lymphocyteCytotoxic T cell responsesT cell responsesCancer vaccine designCholera toxin B subunitToxin B subunitB-cell epitopesMUC1 vaccineTumor burdenCancer vaccinesTh1 cellsT cellsT lymphocytesMouse modelCell epitopesTumor growthCell responsesTumor tissueVaccine designTumor MUC1Antigen designVaccineMUC1 peptide
2014
Relative motions between left flipper and dorsal fin domains favour P2X4 receptor activation
Zhao W, Wang J, Ma X, Yang Y, Liu Y, Huang L, Fan Y, Cheng X, Chen H, Wang R, Yu Y. Relative motions between left flipper and dorsal fin domains favour P2X4 receptor activation. Nature Communications 2014, 5: 4189. PMID: 24943126, DOI: 10.1038/ncomms5189.Peer-Reviewed Original ResearchConceptsAllosteric changesChannel gatingLeft flipperP2X4 receptorDorsal fin domainAllosteric eventsP2X4 receptor activationPhysiological functionsResidues leadFin domainHydrophobic interactionsEssential roleExtracellular ATPFundamental processesZinc bridgesChannel activationReceptor activationDorsal finP2X receptorsReceptorsGatingDomainActivationL217V291