2022
Identification of substrates of palmitoyl protein thioesterase 1 highlights roles of depalmitoylation in disulfide bond formation and synaptic function
Gorenberg EL, Tieze S, Yücel B, Zhao HR, Chou V, Wirak GS, Tomita S, Lam TT, Chandra SS. Identification of substrates of palmitoyl protein thioesterase 1 highlights roles of depalmitoylation in disulfide bond formation and synaptic function. PLOS Biology 2022, 20: e3001590. PMID: 35358180, PMCID: PMC9004782, DOI: 10.1371/journal.pbio.3001590.Peer-Reviewed Original ResearchConceptsPalmitoyl-protein thioesterase 1Disulfide bond formationNeuronal ceroid lipofuscinosisPosttranslational modificationsRole of PPT1Identification of substratesResin-assisted captureEnzyme palmitoyl-protein thioesterase 1Synaptic adhesion moleculesNeurodegenerative diseasesMature proteinMitochondrial proteinsMolecular dissectionPutative substratesDepalmitoylationKnockout mouse brainFunction mutationsStringent screenMolecular pathwaysSynapse functionDisulfide bondsProteinDevastating neurodegenerative diseaseDisease mechanismsSynaptic function
2021
Liver-Dependent Lung Remodeling during Systemic Inflammation Shapes Responses to Secondary Infection.
Odom CV, Kim Y, Burgess CL, Baird LA, Korkmaz FT, Na E, Shenoy AT, Arafa EI, Lam TT, Jones MR, Mizgerd JP, Traber KE, Quinton LJ. Liver-Dependent Lung Remodeling during Systemic Inflammation Shapes Responses to Secondary Infection. The Journal Of Immunology 2021, 207: 1891-1902. PMID: 34470857, PMCID: PMC8631467, DOI: 10.4049/jimmunol.2100254.Peer-Reviewed Original ResearchConceptsSecondary lung infectionAcute phase responseLung infectionSecondary infectionHepatic acute phase responseIntact liver functionSystemic inflammatory challengeAcute phase changesSignificant transcriptional alterationsWild-type miceHepatocyte-specific deletionPneumonic miceSecondary pneumoniaSystemic inflammationCytokine responsesLiver functionImmunological responsivenessInflammatory challengeLung remodelingLittermate miceLung homeostasisImmune activityLungGene signaturePneumonia
2017
Loss of TMEM106B Ameliorates Lysosomal and Frontotemporal Dementia-Related Phenotypes in Progranulin-Deficient Mice
Klein ZA, Takahashi H, Ma M, Stagi M, Zhou M, Lam TT, Strittmatter SM. Loss of TMEM106B Ameliorates Lysosomal and Frontotemporal Dementia-Related Phenotypes in Progranulin-Deficient Mice. Neuron 2017, 95: 281-296.e6. PMID: 28728022, PMCID: PMC5558861, DOI: 10.1016/j.neuron.2017.06.026.Peer-Reviewed Original ResearchConceptsLysosomal protein levelsFrontotemporal lobar degenerationProtein levelsMultiple lysosomal enzymesLysosomal enzymesV0 subunitsTMEM106B geneProteomic analysisProgranulin-deficient miceExtent of neurodegenerationCommon neurodegenerative disorderLysosomal acidificationLysosomal enzyme levelsProtein 1Microglial accumulationRisk modificationFTLD riskBehavioral abnormalitiesRetinal degenerationNeurodegenerative disordersFrontotemporal dementiaGRNTMEM106BFunctional relationshipEnzyme levels
2016
MKK3 influences mitophagy and is involved in cigarette smoke-induced inflammation
Mannam P, Rauniyar N, Lam TT, Luo R, Lee PJ, Srivastava A. MKK3 influences mitophagy and is involved in cigarette smoke-induced inflammation. Free Radical Biology And Medicine 2016, 101: 102-115. PMID: 27717867, DOI: 10.1016/j.freeradbiomed.2016.10.001.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCigarette SmokingGene Expression ProfilingGene Expression RegulationHumansInflammationInterleukin-1betaInterleukin-6MacrophagesMAP Kinase Kinase 3MiceMice, Inbred C57BLMice, KnockoutMitochondriaMitophagyNF-kappa BOxidative PhosphorylationPlant ExtractsPrimary Cell CulturePulmonary Disease, Chronic ObstructiveReactive Oxygen SpeciesTobaccoTumor Necrosis Factor-alphaConceptsCigarette smoke extractCigarette smokeCSE treatmentInflammatory responseLung tissueCigarette smoke-induced inflammationWild typeSerum pro-inflammatory cytokinesSmoke-induced inflammationProgression of COPDMitochondrial dysfunctionReactive oxygen speciesPro-inflammatory cytokinesInflammatory cytokine productionPrimary risk factorAssociated inflammatory responsePatient's lung tissueMouse lung tissueMitochondrial functionDual-specificity protein kinaseRespiratory capacitySpare respiratory capacityAirflow obstructionProtein kinase kinase 3CSE exposureNetrin‐1 Regulates Fibrocyte Accumulation in the Decellularized Fibrotic Sclerodermatous Lung Microenvironment and in Bleomycin‐Induced Pulmonary Fibrosis
Sun H, Zhu Y, Pan H, Chen X, Balestrini JL, Lam TT, Kanyo JE, Eichmann A, Gulati M, Fares WH, Bai H, Feghali-Bostwick CA, Gan Y, Peng X, Moore MW, White ES, Sava P, Gonzalez AL, Cheng Y, Niklason LE, Herzog EL. Netrin‐1 Regulates Fibrocyte Accumulation in the Decellularized Fibrotic Sclerodermatous Lung Microenvironment and in Bleomycin‐Induced Pulmonary Fibrosis. Arthritis & Rheumatology 2016, 68: 1251-1261. PMID: 26749424, PMCID: PMC5547894, DOI: 10.1002/art.39575.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibiotics, AntineoplasticAntibodies, NeutralizingBiomechanical PhenomenaBleomycinCase-Control StudiesCell DifferentiationCollagenCollagen Type ICollagen Type I, alpha 1 ChainFibrosisFlow CytometryFluorescent Antibody TechniqueHeterozygoteHumansLeukocyte Common AntigensLeukocytes, MononuclearLungLung Diseases, InterstitialMiceMice, KnockoutMicroscopy, Electron, ScanningNerve Growth FactorsNetrin-1ProteomicsPulmonary FibrosisReverse Transcriptase Polymerase Chain ReactionScleroderma, SystemicTissue ScaffoldsTumor Suppressor ProteinsConceptsSSc-related interstitial lung diseaseInterstitial lung diseaseFibrocyte accumulationNetrin-1Lung extracellular matrixPulmonary fibrosisLung scaffoldsBleomycin-Induced Pulmonary FibrosisPeripheral blood mononuclear cellsBlood mononuclear cellsHealthy control subjectsNovel therapeutic targetSystemic sclerosisExtracellular matrixLung fibrosisLung diseaseMononuclear cellsControl subjectsLung microenvironmentHealthy controlsScleroderma patientsAberrant anatomyLung matrixPatientsTherapeutic target
2015
Neuronal ceroid lipofuscinosis with DNAJC5/CSPα mutation has PPT1 pathology and exhibit aberrant protein palmitoylation
Henderson MX, Wirak GS, Zhang YQ, Dai F, Ginsberg SD, Dolzhanskaya N, Staropoli JF, Nijssen PC, Lam TT, Roth AF, Davis NG, Dawson G, Velinov M, Chandra SS. Neuronal ceroid lipofuscinosis with DNAJC5/CSPα mutation has PPT1 pathology and exhibit aberrant protein palmitoylation. Acta Neuropathologica 2015, 131: 621-637. PMID: 26659577, PMCID: PMC4791186, DOI: 10.1007/s00401-015-1512-2.Peer-Reviewed Original ResearchConceptsNeuronal ceroid lipofuscinosesProtein palmitoylationDisease pathwaysPalmitoyl-protein thioesterase 1Forms of NCLEnzyme palmitoyl-protein thioesterase 1Disease-associated proteinsCommon disease pathwaysNCL genesQuantitative proteomicsCSPα mutationsSpecific enzymatic activityCSPαFunctional linkNeuronal ceroid lipofuscinosisGlobal changePPT1Synaptic proteinsEnzymatic activityCeroid lipofuscinosesPalmitoylationGenesCeroid lipofuscinosisNeurodegenerative disordersProteinMKK3 deletion improves mitochondrial quality
Srivastava A, McGinniss J, Wong Y, Shinn AS, Lam TT, Lee PJ, Mannam P. MKK3 deletion improves mitochondrial quality. Free Radical Biology And Medicine 2015, 87: 373-384. PMID: 26119780, DOI: 10.1016/j.freeradbiomed.2015.06.024.Peer-Reviewed Original ResearchConceptsLPS treatmentMitochondrial membrane potentialIntensive care unitInflammatory cytokine releaseMAP kinase kinase 3Potential therapeutic targetBetter mitochondrial functionMitochondrial functionMitochondrial qualityMouse embryonic fibroblastsCare unitExcessive inflammationCytokine releaseInhibition of mitophagyInflammatory diseasesCytokine secretionInflammatory responseTherapeutic targetLipopolysaccharide (LPS) stimulationSeptic injuryRole of mitophagyMajor causeOxidant productionSevere responseSepsis
2014
Inhibitor of the Tyrosine Phosphatase STEP Reverses Cognitive Deficits in a Mouse Model of Alzheimer's Disease
Xu J, Chatterjee M, Baguley TD, Brouillette J, Kurup P, Ghosh D, Kanyo J, Zhang Y, Seyb K, Ononenyi C, Foscue E, Anderson GM, Gresack J, Cuny GD, Glicksman MA, Greengard P, Lam TT, Tautz L, Nairn AC, Ellman JA, Lombroso PJ. Inhibitor of the Tyrosine Phosphatase STEP Reverses Cognitive Deficits in a Mouse Model of Alzheimer's Disease. PLOS Biology 2014, 12: e1001923. PMID: 25093460, PMCID: PMC4122355, DOI: 10.1371/journal.pbio.1001923.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmino Acid SequenceAnimalsBenzothiepinsCatalytic DomainCell DeathCerebral CortexCognition DisordersCysteineDisease Models, AnimalEnzyme InhibitorsHigh-Throughput Screening AssaysHumansMaleMice, Inbred C57BLMice, KnockoutMolecular Sequence DataNeuronsPhosphorylationPhosphotyrosineProtein Tyrosine Phosphatases, Non-ReceptorSubstrate SpecificityConceptsInhibitors of stepsSpecificity of inhibitorsIsoxazolepropionic acid receptor (AMPAR) traffickingCatalytic cysteinePTP inhibitorsTyrosine phosphataseTyrosine phosphorylationSecondary assaysSTEP KO miceReceptor traffickingFirst large-scale effortN-methyl-D-aspartate receptorsPyk2 activitySTEP inhibitorLarge-scale effortsNovel therapeutic targetSynaptic functionAlzheimer's diseaseNeurodegenerative disordersCortical cellsTherapeutic targetERK1/2Specificity experimentsPhosphataseInhibitorsNonenzymatic domains of Kalirin7 contribute to spine morphogenesis through interactions with phosphoinositides and Abl
Ma XM, Miller MB, Vishwanatha KS, Gross MJ, Wang Y, Abbott T, Lam TT, Mains RE, Eipper BA. Nonenzymatic domains of Kalirin7 contribute to spine morphogenesis through interactions with phosphoinositides and Abl. Molecular Biology Of The Cell 2014, 25: 1458-1471. PMID: 24600045, PMCID: PMC4004595, DOI: 10.1091/mbc.e13-04-0215.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalpainCells, CulturedDendritic SpinesGuanine Nucleotide Exchange FactorsHippocampusMice, KnockoutNeuronsOncogene Proteins v-ablPeptide FragmentsPhosphatidylinositolsPhosphorylationProtein Processing, Post-TranslationalProtein Structure, TertiaryProteolysisRats, Sprague-DawleySynapsesTransferrinConceptsGDP/GTP exchange factorSec14 domainSpectrin repeatsSpine morphogenesisNon-receptor tyrosine kinaseGTP exchange factorSpine formationNatural splice variantSpectrin repeat domainReceptor-mediated endocytosisRho GDP/GTP exchange factorDrosophila orthologueMembrane traffickingPhosphomimetic mutationExchange factorCalpain-mediated degradationRepeat domainTruncation mutantsTyrosine kinaseGenetic studiesCellular membranesSplice variantsRepeatsNonneuronal cellsMorphogenesis
2011
Cyclin-Dependent Kinase 5 Regulates PSD-95 Ubiquitination in Neurons
Bianchetta MJ, Lam TT, Jones SN, Morabito MA. Cyclin-Dependent Kinase 5 Regulates PSD-95 Ubiquitination in Neurons. Journal Of Neuroscience 2011, 31: 12029-12035. PMID: 21849563, PMCID: PMC3190401, DOI: 10.1523/jneurosci.2388-11.2011.Peer-Reviewed Original ResearchConceptsAMPA receptor endocytosisClathrin adaptor protein complex AP-2Receptor endocytosisAP-2Protein complex AP-2PSD-95Cdk5 activityMajor postsynaptic scaffolding proteinCyclin-dependent kinase 5Interaction of MDM2Β-adaptinNonproteolytic functionsUbiquitin E3Scaffolding proteinUbiquitinationMolecular mechanismsActivator p35Kinase 5Postsynaptic scaffolding proteinGenetic reductionPSD-95 protein levelsNMDA receptor stimulationProtein levelsEndocytosisNeurodegenerative diseases