2025
Adaptation to Volumetric Compression Drives an Apoptosis-Resistant and Invasive Phenotype in Liver Cancer.
Gong X, Ogino N, Leite M, Zhang D, Chen Z, Nguyen R, Liu R, Kruglov E, Flores K, Cabral A, Moreira de M Mendes G, Ehrlich B, Mak M. Adaptation to Volumetric Compression Drives an Apoptosis-Resistant and Invasive Phenotype in Liver Cancer. Cancer Research 2025 PMID: 40387600, DOI: 10.1158/0008-5472.can-24-0859.Peer-Reviewed Original ResearchEpithelial-to-mesenchymal transition genesLiver cancerResistance to apoptosisCell state transitionsProliferation of tumor cellsYAP nuclear translocationCancer cell invasionIntracellular calcium signalingLiver cancer developmentTranscriptional dynamicsRac1 activationCellular protrusionsInhibiting Rac1Apoptosis-resistantTranscriptional changesInvasive phenotypeIntracellular calciumTumor cellsCell invasionNuclear translocationCancer developmentCalcium signalingTransition genesCancer cellsLiver-specific markersDysregulated calcium signaling in the aged macaque entorhinal cortex associated with tau hyperphosphorylation
Bathla S, Datta D, Bolat D, Woo E, Duque A, Arellano J, Arnsten A, Nairn A. Dysregulated calcium signaling in the aged macaque entorhinal cortex associated with tau hyperphosphorylation. Frontiers In Aging Neuroscience 2025, 17: 1549770. PMID: 40365352, PMCID: PMC12069431, DOI: 10.3389/fnagi.2025.1549770.Peer-Reviewed Original ResearchTau pathologyTau hyperphosphorylationAlzheimer's diseaseAssociated with tau hyperphosphorylationSoluble phosphorylated tauSporadic Alzheimer's diseaseCalcium signalingDysregulated calcium signalingTau etiologyEarly stages of ADHyperphosphorylationSignaling pathwayHuman ADInflammatory signaling pathwaysCalpain-2Stages of ADMolecular processesHydrolyze cAMPTauEntorhinal cortexCarboxypeptidase IIGlutamate carboxypeptidase IIDephosphorylationA force-sensitive adhesion GPCR is required for equilibrioception
Yang Z, Zhou S, Zhang Q, Song Z, Liu W, Sun Y, Wang M, Fu X, Zhu K, Guan Y, Qi J, Wang X, Sun Y, Lu Y, Ping Y, Xi Y, Teng Z, Xu L, Xiao P, Xu Z, Xiong W, Qin W, Yang W, Yi F, Chai R, Yu X, Sun J. A force-sensitive adhesion GPCR is required for equilibrioception. Cell Research 2025, 35: 243-264. PMID: 39966628, PMCID: PMC11958651, DOI: 10.1038/s41422-025-01075-x.Peer-Reviewed Original ResearchTransmembrane channel-like protein 1G protein-coupled receptorsUtricular hair cellsHair cellsIncreased open probabilityAdhesion GPCRsVestibular hair cellsGlutamate releaseOpen probabilityApical membraneMET responsesVestibular functionCalcium signalingApical surfaceProtein 1Lphn2Heterologous systemsMechanosensitive G-protein-coupled receptorsMetSMiceFunctional analysisCellsExploring Calcium Channels as Potential Therapeutic Targets in Blast Traumatic Brain Injury
Wachtler N, O’Brien R, Ehrlich B, McGuone D. Exploring Calcium Channels as Potential Therapeutic Targets in Blast Traumatic Brain Injury. Pharmaceuticals 2025, 18: 223. PMID: 40006037, PMCID: PMC11859800, DOI: 10.3390/ph18020223.Peer-Reviewed Original ResearchCalcium signalingCalcium channelsTherapeutic strategiesCalcium homeostasisFunction of calcium channelsDysregulated calcium signalingModulation of injuryTraumatic brain injuryBrain injuryLoss of calcium homeostasisBlast-related traumatic brain injuryDevelopment of neuroprotective interventionsIntracellular calcium dynamicsPlasma membrane stabilityExtracellular calciumBlast traumatic brain injuryPreclinical modelsTherapeutic outcomesNeuroprotective interventionsMembrane abnormalitiesPharmacological inhibitorsNeuronal somataExclusion criteriaCalcium dynamicsSecondary injury
2024
Compartmentalized pooling generates orientation selectivity in wide-field amacrine cells
Lei W, Clark D, Demb J. Compartmentalized pooling generates orientation selectivity in wide-field amacrine cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2411130121. PMID: 39602271, PMCID: PMC11626119, DOI: 10.1073/pnas.2411130121.Peer-Reviewed Original ResearchConceptsOrientation selectivityBand-pass spatial frequency tuningVisual systemReceptive fieldsSpatial frequency tuningWide-field amacrine cellsReceptive field modelOrientation detectionKappa-opioid receptorsAmacrine cellsDetecting orientationVisual sceneFrequency tuningGlycinergic inhibitionOpioid receptorsField modelSpecific membrane resistanceExcitatory inputSynaptic inputsCalcium imagingMouse retinaCalcium signalingDendritic compartmentsMicrocircuit levelPolarizationMitochondria as determinants of reproductive senescence and competence: implications for diagnosis of embryo competence in assisted reproduction
Yildirim R, Seli E. Mitochondria as determinants of reproductive senescence and competence: implications for diagnosis of embryo competence in assisted reproduction. Human Reproduction 2024, 39: 2160-2170. PMID: 39066612, DOI: 10.1093/humrep/deae171.Peer-Reviewed Original ResearchMultiple quality control mechanismsMitochondrial unfolded protein responseMitochondrial DNA copy numberUnfolded protein responseQuality control mechanismsDNA copy numberMitochondrial networkRegulate calcium signalingMitochondrial dynamicsReproductive successMitochondrial quantityProtein responseDinucleotide contentModulate apoptosisOxidative phosphorylationCellular pathwaysCopy numberMitochondrial dysfunctionMitochondriaCalcium signalingEmbryo competenceMembrane potentialAssisted reproductionDiagnostic targetsReproductive senescenceNeutrophils insert elastase into hepatocytes to regulate calcium signaling in alcohol-associated hepatitis
Ogino N, Leite M, Guerra M, Kruglov E, Asashima H, Hafler D, Ito T, Pereira J, Peiffer B, Sun Z, Ehrlich B, Nathanson M. Neutrophils insert elastase into hepatocytes to regulate calcium signaling in alcohol-associated hepatitis. Journal Of Clinical Investigation 2024, 134: e171691. PMID: 38916955, PMCID: PMC11324315, DOI: 10.1172/jci171691.Peer-Reviewed Original ResearchAlcohol-associated hepatitisReduced cell proliferationCalcium channel expressionCalcium signaling mechanismsIntracellular calcium channelsCell proliferationRegulate calcium signalingNeutrophil extracellular trapsChannel expressionNeutrophil granule proteinsCalcium channelsNeutrophil infiltrationPatient specimensGranule proteasesMouse modelHealthy subjectsLiver diseaseExtracellular trapsCalcium signalingSerpin E2NeutrophilsElastase activityHepatitisTissue remodelingSignaling mechanismsCalcium signalling and transport in the kidney
Staruschenko A, Alexander R, Caplan M, Ilatovskaya D. Calcium signalling and transport in the kidney. Nature Reviews Nephrology 2024, 20: 541-555. PMID: 38641658, PMCID: PMC12036682, DOI: 10.1038/s41581-024-00835-z.Peer-Reviewed Original ResearchCalcium channelsCalcium levelsCalcium-binding proteinSerum calcium levelsOptimal bone mineralizationPolycystic kidney diseaseIntracellular signaling mechanismsIntracellular second messengersRegulate calcium levelsCalcium handlingSevere complicationsFiltered calciumKidney diseaseCalcium transportRenal cellsCalcium homeostasisCalcium signalingFormation of kidney stonesCalcium dysregulationPhysiological stimuliKidney stonesBone mineralizationKidneySecond messengersSignaling mechanismsGonadal hormone deprivation regulates response to tibolone in neurodegenerative pathways
McGovern A, Arevalo M, Ciordia S, Garcia-Segura L, Barreto G. Gonadal hormone deprivation regulates response to tibolone in neurodegenerative pathways. The Journal Of Steroid Biochemistry And Molecular Biology 2024, 241: 106520. PMID: 38614433, DOI: 10.1016/j.jsbmb.2024.106520.Peer-Reviewed Original ResearchHormone therapyEfficacy of hormone therapyEffects of hormone therapyPathways of neurodegenerationBilateral oophorectomyHormone deprivationAndrogen pathwayIncreased risk of neurodegenerationTherapeutic efficacyTiboloneOxidative phosphorylationIncreased riskProteomic analysisCalcium signalingCellular respirationHormonal declineNeurodegenerative pathwaysDrug typeRisk of neurodegenerationInterconnected pathwaysPathwayNeurodegenerationSexBlood epigenome-wide association studies of suicide attempt in adults with bipolar disorder
Mirza S, Lima C, Del Favero-Campbell A, Rubinstein A, Topolski N, Cabrera-Mendoza B, Kovács E, Blumberg H, Richards J, Williams A, Wemmie J, Magnotta V, Fiedorowicz J, Gaine M, Walss-Bass C, Quevedo J, Soares J, Fries G. Blood epigenome-wide association studies of suicide attempt in adults with bipolar disorder. Translational Psychiatry 2024, 14: 70. PMID: 38296944, PMCID: PMC10831084, DOI: 10.1038/s41398-024-02760-y.Peer-Reviewed Original ResearchConceptsEpigenome-wide association studiesDifferentially methylated regionsDifferentially methylated positionsAssociation studiesCo-methylation network analysisBipolar disorderDNA methylation patternsSuicide attemptsReplication cohortHistory of SAGene ontology analysisSignificant CpG sitesMethylation patternsDNA methylationCpG sitesOntology analysisImmune-related genesEnrichment analysisNon-psychiatric controlsCalcium signalingGenesDNAClinical interviewSA historyNetwork analysis
2023
Localization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer’s disease
Datta D, Perone I, Morozov Y, Arellano J, Duque A, Rakic P, van Dyck C, Arnsten A. Localization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer’s disease. Cerebral Cortex 2023, 33: 11501-11516. PMID: 37874022, PMCID: PMC10724870, DOI: 10.1093/cercor/bhad382.Peer-Reviewed Original ResearchConceptsHCN1 channelsTau pathologyGlutamate synapsesEntorhinal cortexCalcium actionInternal calcium releaseEntorhinal cortex stellate cellsDorsolateral prefrontal cortexSusceptible neuronsInitial pathologySelective vulnerabilityEtiological factorsTau phosphorylationStellate cellsAlzheimer's diseaseSpecific neuronsCalcium releasePrefrontal cortexCortexSynapse strengthPathologyCalcium signalingCalbindinDiseaseNeuronsA CUG-initiated CATSPERθ functions in the CatSper channel assembly and serves as a checkpoint for flagellar trafficking
Huang X, Miyata H, Wang H, Mori G, Iida-Norita R, Ikawa M, Percudani R, Chung J. A CUG-initiated CATSPERθ functions in the CatSper channel assembly and serves as a checkpoint for flagellar trafficking. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2304409120. PMID: 37725640, PMCID: PMC10523455, DOI: 10.1073/pnas.2304409120.Peer-Reviewed Original ResearchConceptsChannel assemblySperm flagellaTransmembrane domain-containing proteinsSperm tail formationDomain-containing proteinsCatSper channel complexMale fertilityFlagellar traffickingMacromolecular complexesTail formationPhysiological roleSuccessful fertilizationCalcium signalingCatSper channelsFlagellaGenetic abrogationChannel complexNormal expressionDimer formationSpermatid cellsProteinCheckpointHyperactivated motilityAssemblyPotential roleCalcium signaling in chemotherapy-induced neuropathy
Fonseca M, Marazzi-Diniz P, Leite M, Ehrlich B. Calcium signaling in chemotherapy-induced neuropathy. Cell Calcium 2023, 113: 102762. PMID: 37244172, DOI: 10.1016/j.ceca.2023.102762.Peer-Reviewed Original ResearchConceptsChemotherapy-induced peripheral neuropathyNeuronal calcium sensor-1Chemotherapy-induced cognitive impairmentMultiple chemotherapy regimensChemotherapy-induced neuropathyDisease-modifying treatmentsQuality of lifeChemotherapy regimensChemotherapy dosePeripheral neuropathyPathophysiological cascadePatient outcomesOptimal chemotherapySide effectsCognitive impairmentChemotherapeutic agentsTarget toxicityCancer cellsSensitive CaCalcium signalingOff-target effectsNeuropathyTaxanesTreatmentMolecular mechanisms
2022
Activated astrocytes attenuate neocortical seizures in rodent models through driving Na+-K+-ATPase
Zhao J, Sun J, Zheng Y, Zheng Y, Shao Y, Li Y, Fei F, Xu C, Liu X, Wang S, Ruan Y, Liu J, Duan S, Chen Z, Wang Y. Activated astrocytes attenuate neocortical seizures in rodent models through driving Na+-K+-ATPase. Nature Communications 2022, 13: 7136. PMID: 36414629, PMCID: PMC9681834, DOI: 10.1038/s41467-022-34662-2.Peer-Reviewed Original ResearchConceptsAnti-seizure effectsNa+-K+-ATPasePyramidal neuronsNeocortical seizuresRodent modelsInhibition of pyramidal neuronsExcitation-inhibition imbalanceTreatment of intractable epilepsyNa+-K+-ATPase activityMinimal side effectsAnti-seizure strategyAstrocyte-neuron interactionsOptogenetic activationTherapeutic windowIntractable epilepsyEpilepsy modelSide effectsCalcium signalingTherapeutic effectSeizuresActivity-dependentEpileptic seizuresAstrocyte stimulationAstrocytesPotential targetCalcium-Permeable Channels Cooperation for Rheumatoid Arthritis: Therapeutic Opportunities
Liang H, Yin H, Li S, Chen Y, Zhao Y, Hu W, Zhou R. Calcium-Permeable Channels Cooperation for Rheumatoid Arthritis: Therapeutic Opportunities. Biomolecules 2022, 12: 1383. PMID: 36291594, PMCID: PMC9599458, DOI: 10.3390/biom12101383.Peer-Reviewed Original ResearchConceptsPathogenesis of RARheumatoid arthritisCalcium-permeable channelsIntra-articular inflammationCommon autoimmune diseaseTreatment of RAEntry of CaDrug targetsSynovial invasionPatients' qualityAutoimmune diseasesNovel drug targetsCartilage damageArthritisTherapeutic opportunitiesPathological processesCalcium signalingInflammationPathogenesisSpecific roleRAHuman cellsTargetCell membraneDiseaseUnusual Molecular Regulation of Dorsolateral Prefrontal Cortex Layer III Synapses Increases Vulnerability to Genetic and Environmental Insults in Schizophrenia
Arnsten AFT, Woo E, Yang S, Wang M, Datta D. Unusual Molecular Regulation of Dorsolateral Prefrontal Cortex Layer III Synapses Increases Vulnerability to Genetic and Environmental Insults in Schizophrenia. Biological Psychiatry 2022, 92: 480-490. PMID: 35305820, PMCID: PMC9372235, DOI: 10.1016/j.biopsych.2022.02.003.Peer-Reviewed Original ResearchConceptsEnvironmental insultsMore superficial layersDorsolateral prefrontal cortexPrimate dlPFCInflammatory mechanismsInflammatory insultKynurenic acidNMDA receptorsReceptor neurotransmissionDendritic spinesLayer IIICAMP/PKAGlutamatergic synapsePrefrontal cortexInsultPotassium channelsNeurotransmissionCalcium signalingSynapsesGenetic insultsSuperficial layersSchizophreniaSpineCortexNeuromodulation
2021
Physiologically detectable bisphenol A impairs human sperm functions by reducing protein-tyrosine phosphorylation
Li N, Kang H, Peng Z, Wang H, Weng S, Zeng X. Physiologically detectable bisphenol A impairs human sperm functions by reducing protein-tyrosine phosphorylation. Ecotoxicology And Environmental Safety 2021, 221: 112418. PMID: 34146982, DOI: 10.1016/j.ecoenv.2021.112418.Peer-Reviewed Original ResearchConceptsHuman sperm viabilityHuman sperm functionHuman spermExposure of BPASperm functionProgesterone-induced acrosome reactionProtein tyrosine phosphorylationProtein tyrosine phosphorylation levelsAcrosome reactionMale infertilityHealthy peopleMouse sperm motilitySperm viabilityCalcium signalingPhosphorylation levelsTyrosine phosphorylation levelsBisphenol ASperm motilityProgressive motilityHyperactivationMotilityDetectable concentrationRemarkable declineTyrosine phosphorylationPlastic monomers
2020
Inositol 1,4,5 trisphosphate receptors in secretory epithelial cells of the gastrointestinal tract
Lemos F, Guerra M, de Fátima Leite M. Inositol 1,4,5 trisphosphate receptors in secretory epithelial cells of the gastrointestinal tract. Current Opinion In Physiology 2020, 17: 169-174. DOI: 10.1016/j.cophys.2020.08.003.Peer-Reviewed Original ResearchEpithelial cellsFatty liver diseaseIntracellular calcium signalingLiver diseaseAcute pancreatitisSecretory epithelial cellsPathophysiological roleGastrointestinal tractElectrolyte secretionSolid tumorsIntracellular Ca2Main intracellular Ca2Number of diseasesDiseaseCell proliferationCalcium signalingEnergy metabolismReceptorsMolecular mechanismsSubcellular localizationTrisphosphate receptorPhysiological functionsCellsInositol 1Ca2TRPV4 helps Piezo1 put the squeeze on pancreatic acinar cells
Gorelick F, Nathanson MH. TRPV4 helps Piezo1 put the squeeze on pancreatic acinar cells. Journal Of Clinical Investigation 2020, 130: 2199-2201. PMID: 32281947, PMCID: PMC7190901, DOI: 10.1172/jci136525.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsCalcium signalingAcinar cellsPlasma membrane calcium channelsGenetic deletion modelsMembrane calcium channelsCytosolic calcium levelsCell culture systemDeletion modelTransient receptor potential vanilloidPathogenesis of pancreatitisSignalingCulture systemCellsPathwayStimulation pathwayCalcium channelsCalcium Signaling in Cholangiocytes
Hernandez E, Nathanson M. Calcium Signaling in Cholangiocytes. 2020, 105-111. DOI: 10.1201/9780367813888-10.Peer-Reviewed Original Research
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