2024
Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains
Zhu B, Park J, Coffey S, Russo A, Hsu I, Wang J, Su C, Chang R, Lam T, Gopal P, Ginsberg S, Zhao H, Hafler D, Chandra S, Zhang L. Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains. Science Translational Medicine 2024, 16: eabo1997. PMID: 39475571, DOI: 10.1126/scitranslmed.abo1997.Peer-Reviewed Original ResearchConceptsProteomic analysisAlzheimer's diseasePrefrontal cortexBrain cell typesGenetics of PDParkinson's diseaseCell-cell interactionsChaperone expressionSingle-nucleus transcriptomesExpressed genesTranscriptional changesPostmortem human brainPostmortem brain tissueDiseased brainSynaptic proteinsSingle-cellDown-regulationBrain cell populationsBrain regionsCell typesNeurodegenerative disordersLate-stage PDParkinson's disease brainsDisease etiologyNeuronal vulnerabilityProteomic Profile of Circulating Extracellular Vesicles in the Brain after Δ9-Tetrahydrocannabinol Inhalation
Lallai V, Lam T, Garcia-Milian R, Chen Y, Fowler J, Manca L, Piomelli D, Williams K, Nairn A, Fowler C. Proteomic Profile of Circulating Extracellular Vesicles in the Brain after Δ9-Tetrahydrocannabinol Inhalation. Biomolecules 2024, 14: 1143. PMID: 39334909, PMCID: PMC11430348, DOI: 10.3390/biom14091143.Peer-Reviewed Original ResearchConceptsImmediate early gene c-fosChronic THC exposureEarly gene c-fosCannabinoid 1 receptorGene c-fosSex-specific mannerTHC exposurePsychoactive componentExtracellular vesiclesCentral signaling mechanismDrug effectsTHCChoroid plexus epithelial cellsFemale ratsC-fosPlexus epithelial cellsBrainCannabisRelease of EVsRegulate intercellular communicationCerebrospinal fluidEpithelial cellsIntercellular signaling mediatorsEV signalingIntercellular communicationCell-specific cross-talk proteomics reveals cathepsin B signaling as a driver of glioblastoma malignancy near the subventricular zone
Norton E, Whaley L, Jones V, Brooks M, Russo M, Morderer D, Jessen E, Schiapparelli P, Ramos-Fresnedo A, Zarco N, Carrano A, Rossoll W, Asmann Y, Lam T, Chaichana K, Anastasiadis P, Quiñones-Hinojosa A, Guerrero-Cázares H. Cell-specific cross-talk proteomics reveals cathepsin B signaling as a driver of glioblastoma malignancy near the subventricular zone. Science Advances 2024, 10: eadn1607. PMID: 39110807, PMCID: PMC11305394, DOI: 10.1126/sciadv.adn1607.Peer-Reviewed Original ResearchConceptsBrain tumor-initiating cellsLateral ventricleNeuronal maturationMalignancy-associated phenotypesSubventricular zone contactIncreased expression of cathepsin BMalignant primary brain tumorTumor-initiating cellsAggressive malignant primary brain tumorPrimary brain tumorTumor microenvironment researchExpression of cathepsin BNeural stem/progenitor cellsCathepsin BInduction of senescenceStem/progenitor cellsCell-intrinsicSubventricular zoneCross-talkTherapeutic strategiesBrain tumorsIncreased expressionGBM biologyLentiviral knockdownGlioblastoma
2023
Peripheral signature of altered synaptic integrity in young onset cannabis use disorder: A proteomic study of circulating extracellular vesicles
Ganesh S, Lam T, Garcia-Milian R, D'Souza D, Nairn A, Elgert K, Eitan E, Ranganathan M. Peripheral signature of altered synaptic integrity in young onset cannabis use disorder: A proteomic study of circulating extracellular vesicles. The World Journal Of Biological Psychiatry 2023, 24: 603-613. PMID: 36994633, PMCID: PMC10471733, DOI: 10.1080/15622975.2023.2197039.Peer-Reviewed Original ResearchConceptsNeuron-derived extracellular vesiclesLabel-free quantification mass spectrometryProteomic studiesCannabis use disorderExtracellular vesiclesMass spectrometry proteomic analysisDifferential proteomic profilesAdapter proteinProteomic analysisPost-synaptic densityPeripheral signatureMolecular basisProteomic profilesProteinMarkers of neuropathologyBrain tissue samplesSynaptic pathologyVesiclesSynaptic integrityImmunoaffinity methodUse disordersFunctional integrityImportant insightsNeuropathologyPilot studyDopamine transporter and synaptic vesicle sorting defects underlie auxilin-associated Parkinson’s disease
Vidyadhara D, Somayaji M, Wade N, Yücel B, Zhao H, Shashaank N, Ribaudo J, Gupta J, Lam T, Sames D, Greene L, Sulzer D, Chandra S. Dopamine transporter and synaptic vesicle sorting defects underlie auxilin-associated Parkinson’s disease. Cell Reports 2023, 42: 112231. PMID: 36920906, PMCID: PMC10127800, DOI: 10.1016/j.celrep.2023.112231.Peer-Reviewed Original ResearchConceptsParkinson's diseaseMotor deficitsDopamine transporterPathogenesis of PDNigral dopaminergic lossProgressive motor deficitsΑ-synuclein pathologyEarly-onset Parkinson's diseaseDopamine sequestrationDopaminergic vulnerabilityDopaminergic lossKO micePresynaptic sitesKO brainNeurochemical analysisDorsal striatumKnockout miceCardinal featuresReuptake kineticsL-DOPADiseaseSynaptic autophagyFunction mutationsDeficitsMice
2022
Proteomic profiling reveals an association between ALDH and oxidative phosphorylation and DNA damage repair pathways in human colon adenocarcinoma stem cells
Wang Y, Chen Y, Garcia-Milian R, Golla JP, Charkoftaki G, Lam TT, Thompson DC, Vasiliou V. Proteomic profiling reveals an association between ALDH and oxidative phosphorylation and DNA damage repair pathways in human colon adenocarcinoma stem cells. Chemico-Biological Interactions 2022, 368: 110175. PMID: 36162455, PMCID: PMC9891852, DOI: 10.1016/j.cbi.2022.110175.Peer-Reviewed Original ResearchConceptsCancer stem cellsProteomic profilingOxidative phosphorylationLabel-free quantitative proteomic analysisDNA damage repair pathwaysQuantitative proteomic analysisAldehyde dehydrogenase familyColon cancer stem cellsCOLO320DM cellsStem cellsNucleotide excision repairDamage repair pathwaysIngenuity Pathway AnalysisCell populationsProteomic analysisProteomic datasetsDehydrogenase familyMetabolic switchProteomic studiesRepair pathwaysCellular pathwaysALDH enzymatic activityCellular survivalExcision repairALDH activitySex- and estrous-cycle dependent dorsal hippocampal phosphoproteomic changes induced by low-dose ketamine
Saland SK, Wilczak K, Voss E, Lam TT, Kabbaj M. Sex- and estrous-cycle dependent dorsal hippocampal phosphoproteomic changes induced by low-dose ketamine. Scientific Reports 2022, 12: 1820. PMID: 35110693, PMCID: PMC8810966, DOI: 10.1038/s41598-022-05937-x.Peer-Reviewed Original ResearchConceptsLow-dose ketamineFemale ratsMale ratsTherapeutic effectIntact adult male ratsNMDA receptor antagonist ketamineAcute low doseKetamine's therapeutic effectsRapid antidepressant actionsAdult male ratsKetamine-induced changesRapid actionAntidepressant actionAntidepressant ketamineHormonal milieuHormone-dependent modulationHormonal statusLow doseKetamineBrain regionsRatsSynaptic signalingPathway activationBi-directional effectsCritical modulator
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 signaturePneumoniaSmall Extracellular Vesicles Control Dendritic Spine Development through Regulation of HDAC2 Signaling
Zhang L, Lin TV, Yuan Q, Sadoul R, Lam TT, Bordey A. Small Extracellular Vesicles Control Dendritic Spine Development through Regulation of HDAC2 Signaling. Journal Of Neuroscience 2021, 41: 3799-3807. PMID: 33741723, PMCID: PMC8084316, DOI: 10.1523/jneurosci.0766-20.2021.Peer-Reviewed Original ResearchConceptsSmall extracellular vesiclesRegulation of HDAC2Extracellular vesiclesSpine developmentCell-cell signalingTranscriptional programsCortical neuronsSEV releaseTranscriptional decreaseDendritic spinesNeuronal developmentNeuron developmentDendritic spine developmentLines of evidenceHDAC2Paracrine communicationAge-dependent decreaseVesiclesPopulations of neuronsRegulationLC-MS/MSHDAC2 levelsSynaptic targetsExcitatory synapsesSpine growth
2020
Granulocyte-Colony Stimulating Factor Reduces Cocaine-Seeking and Downregulates Glutamatergic Synaptic Proteins in Medial Prefrontal Cortex
Hofford RS, Euston TJ, Wilson RS, Meckel KR, Peck EG, Godino A, Landry JA, Calipari ES, Lam TT, Kiraly DD. Granulocyte-Colony Stimulating Factor Reduces Cocaine-Seeking and Downregulates Glutamatergic Synaptic Proteins in Medial Prefrontal Cortex. Journal Of Neuroscience 2020, 41: 1553-1565. PMID: 33361463, PMCID: PMC7896012, DOI: 10.1523/jneurosci.1452-20.2020.Peer-Reviewed Original ResearchConceptsGranulocyte-colony stimulating factorMedial prefrontal cortexPsychostimulant use disordersPrefrontal cortexNucleus accumbensUse disordersDrug AdministrationMale Sprague-Dawley ratsMajor public health issueG-CSF treatmentSprague-Dawley ratsSynaptic dopamine releasePublic health issueTranslational research strategiesG-CSF effectsCue-induced drugDrug seeking behaviorRapid clinical translationAlters behavioral responsesRecombinant G-CSFReinstatement of cocaineGlutamatergic mechanismsPharmacological treatmentDawley ratsDopamine releaseCerebrospinal fluid proteome evaluation in major depressive disorder by mass spectrometry
Franzen AD, Lam TT, Williams KR, Nairn AC, Duman RS, Sathyanesan M, Kumar V, Carpenter LL, Newton SS. Cerebrospinal fluid proteome evaluation in major depressive disorder by mass spectrometry. BMC Psychiatry 2020, 20: 481. PMID: 32998701, PMCID: PMC7528485, DOI: 10.1186/s12888-020-02874-9.Peer-Reviewed Original ResearchMeSH KeywordsDepressive Disorder, MajorGene Expression ProfilingHumansMass SpectrometryProteomeProteomicsConceptsPR domain zinc finger protein 1Bioinformatics analysisZinc finger protein 1Quantitative mass spectrometryFinger protein 1Potential biological functionsMajor canonical pathwaysPeroxisome proliferator-activated receptor gamma coactivatorProliferator-activated receptor gamma coactivatorCellular functionsCellular movementCellular compromiseCell signalingCellular developmentOrganismal injuryBiological functionsReceptor gamma coactivatorCanonical pathwaysSignal transducerUpstream regulatorTranscription 3Protein profilesDifferential expressionProtein synthesisProteomics software
2019
Integrated multi-omics approach reveals a role of ALDH1A1 in lipid metabolism in human colon cancer cells
Charkoftaki G, Thompson DC, Golla JP, Garcia-Milian R, Lam TT, Engel J, Vasiliou V. Integrated multi-omics approach reveals a role of ALDH1A1 in lipid metabolism in human colon cancer cells. Chemico-Biological Interactions 2019, 304: 88-96. PMID: 30851239, PMCID: PMC7988342, DOI: 10.1016/j.cbi.2019.02.030.Peer-Reviewed Original Research
2018
ProteomicsBrowser: MS/proteomics data visualization and investigation
Peng G, Wilson R, Tang Y, Lam TT, Nairn AC, Williams K, Zhao H. ProteomicsBrowser: MS/proteomics data visualization and investigation. Bioinformatics 2018, 35: 2313-2314. PMID: 30462190, PMCID: PMC6596887, DOI: 10.1093/bioinformatics/bty958.Peer-Reviewed Original ResearchPhosphoproteomic analysis of cocaine memory extinction and reconsolidation in the nucleus accumbens
Torregrossa MM, MacDonald M, Stone KL, Lam TT, Nairn AC, Taylor JR. Phosphoproteomic analysis of cocaine memory extinction and reconsolidation in the nucleus accumbens. Psychopharmacology 2018, 236: 531-543. PMID: 30411139, PMCID: PMC6374162, DOI: 10.1007/s00213-018-5071-9.Peer-Reviewed Original ResearchMeSH KeywordsAmygdalaAnimalsAssociation LearningBasolateral Nuclear ComplexCocaine-Related DisordersCuesExtinction, PsychologicalMaleMental RecallMotivationNucleus AccumbensPhosphoproteinsPhosphorylationProteomicsRatsRats, Sprague-DawleyReceptors, GABA-BRecurrenceSelf AdministrationSignal TransductionConceptsCocaine-cue memoriesCue memoryCue extinctionDifferent memory processesBasolateral amygdalaCocaine-associated cuesSelf-administer cocaineNucleus accumbensBrief cueLikelihood of relapseDrug cuesAudiovisual cuesCue presentationMemory extinctionMemory processesMotivational propertiesReconsolidationCuesMemoryBehavioral conditionsMethodsMale Sprague–Dawley ratsProtein phosphorylationObjectivesThe purposeImportant research goalCross-region analysisIsoform-Level Interpretation of High-Throughput Proteomics Data Enabled by Deep Integration with RNA-seq
Carlyle B, Kitchen RR, Zhang J, Wilson R, Lam T, Rozowsky JS, Williams KR, Sestan N, Gerstein M, Nairn AC. Isoform-Level Interpretation of High-Throughput Proteomics Data Enabled by Deep Integration with RNA-seq. Journal Of Proteome Research 2018, 17: 3431-3444. PMID: 30125121, PMCID: PMC6392456, DOI: 10.1021/acs.jproteome.8b00310.Peer-Reviewed Original ResearchConceptsRNA-seqProteomic dataGene expressionLiquid chromatography-tandem mass spectrometry proteomicsTandem mass spectrometry proteomicsHigh-throughput proteomic dataTranscriptomic profiling methodsDistinct amino acid sequencesTranscript-level expressionAmino acid sequenceMass spectrometry proteomicsHEK293 cell culturesTranslatome dataMost genesProfound functional implicationsProtein isoformsAlternate isoformsGene productsAcid sequenceCellular controlBiosynthetic stateGeneration of peptidesCell typesFunctional relevanceFunctional implications
2017
A multiregional proteomic survey of the postnatal human brain
Carlyle BC, Kitchen RR, Kanyo JE, Voss EZ, Pletikos M, Sousa AMM, Lam TT, Gerstein MB, Sestan N, Nairn AC. A multiregional proteomic survey of the postnatal human brain. Nature Neuroscience 2017, 20: 1787-1795. PMID: 29184206, PMCID: PMC5894337, DOI: 10.1038/s41593-017-0011-2.Peer-Reviewed Original ResearchConceptsProteomic surveyResident plasma membrane proteinsPostnatal human brainProtein dataPlasma membrane proteinsProtein abundance differencesQuantitative tandem mass spectrometryPost-translational eventsWhole transcriptome sequencingRNA expression dataMembrane proteinsFunctional variationExpression dataAbundance differencesBrain regionsTandem mass spectrometryHuman brainSimilar cortical regionsMass spectrometryEarly infancyRNACortical regionsSequencingProteinAbundanceLoss 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
Phosphoproteomic Analysis Reveals a Novel Mechanism of CaMKIIα Regulation Inversely Induced by Cocaine Memory Extinction versus Reconsolidation
Rich MT, Abbott TB, Chung L, Gulcicek EE, Stone KL, Colangelo CM, Lam TT, Nairn AC, Taylor JR, Torregrossa MM. Phosphoproteomic Analysis Reveals a Novel Mechanism of CaMKIIα Regulation Inversely Induced by Cocaine Memory Extinction versus Reconsolidation. Journal Of Neuroscience 2016, 36: 7613-7627. PMID: 27445140, PMCID: PMC4951572, DOI: 10.1523/jneurosci.1108-16.2016.Peer-Reviewed Original ResearchMeSH Keywords1-(5-Isoquinolinesulfonyl)-2-MethylpiperazineAmygdalaAnimalsBenzylaminesCalcium-Calmodulin-Dependent Protein Kinase Type 2CocaineConditioning, OperantCuesEnzyme InhibitorsExtinction, PsychologicalHEK293 CellsHumansMaleMemoryPhosphorylationProteomicsRatsRats, Sprague-DawleySelf AdministrationSerineSignal TransductionSulfonamidesConceptsRelapse-like behaviorMemory extinctionSubsequent cue-induced reinstatementAddiction treatmentDrug-associated memoriesCocaine-associated memoryCue-induced reinstatementRelapse prevention therapySelf-administer cocaineLong-term abstinenceReconsolidation disruptionAbstinence effortsAudiovisual cuesEssential therapeutic goalCocaine memoryMemory strengtheningAmygdala inhibitionDrug useReconsolidationExtinction enhancementAddictive disordersRelapse preventionMemoryCuesEnvironmental cuesNetrin‐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 disordersProtein