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 communication
2023
Common Pathways of Epileptogenesis in Patients With Epilepsy Post–Brain Injury
Misra S, Khan E, Lam T, Mazumder R, Gururangan K, Hickman L, Goswami V, Funaro M, Eldem E, Sansing L, Sico J, Quinn T, Liebeskind D, Montaner J, Kwan P, Mishra N. Common Pathways of Epileptogenesis in Patients With Epilepsy Post–Brain Injury. Neurology 2023, 101: e2243-e2256. PMID: 37550071, PMCID: PMC10727219, DOI: 10.1212/wnl.0000000000207749.Peer-Reviewed Original ResearchConceptsStandardized mean differencePoststroke epilepsyBrain injuryGenetic susceptibilityDisparate time pointsRisk of epileptogenesisLate-onset seizuresDevelopment of epilepsyBlood glucose levelsTraumatic brain injuryMean biomarker levelsIndividual genetic susceptibilityWeb of ScienceReported biomarkersPrimary outcomeEpileptogenic processBiofluid biomarkersBias assessmentBiomarker levelsCommon biological pathwaysEnrichment analysisGlucose levelsHigh riskPrognostic studiesEpilepsy
2022
Sex- 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
Cocaine self-administration induces sex-dependent protein expression in the nucleus accumbens
López AJ, Johnson AR, Euston TJ, Wilson R, Nolan SO, Brady LJ, Thibeault KC, Kelly SJ, Kondev V, Melugin P, Kutlu MG, Chuang E, Lam TT, Kiraly DD, Calipari ES. Cocaine self-administration induces sex-dependent protein expression in the nucleus accumbens. Communications Biology 2021, 4: 883. PMID: 34272455, PMCID: PMC8285523, DOI: 10.1038/s42003-021-02358-w.Peer-Reviewed Original ResearchConceptsProtein expression patternsExpression patternsQuantitative mass spectrometrySubstance use disordersCritical biological variableProteomic functionProtein regulationRegulated proteinsUnique molecular profileNucleus accumbensSexual dimorphismProteomeProtein expressionMolecular substratesDrug-induced plasticityMolecular profileChronic neuropsychiatric conditionsPreclinical evidenceBaseline differencesCocaine administrationReward-associated behaviorsUse disordersMass spectrometryMale subjectsBiological variablesSmall 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 releaseBioactive Plasma Mitochondrial DNA Is Associated With Disease Progression in Scleroderma‐Associated Interstitial Lung Disease
Ryu C, Walia A, Ortiz V, Perry C, Woo S, Reeves BC, Sun H, Winkler J, Kanyo JE, Wang W, Vukmirovic M, Ristic N, Stratton EA, Meena SR, Minasyan M, Kurbanov D, Liu X, Lam TT, Farina G, Gomez JL, Gulati M, Herzog EL. Bioactive Plasma Mitochondrial DNA Is Associated With Disease Progression in Scleroderma‐Associated Interstitial Lung Disease. Arthritis & Rheumatology 2020, 72: 1905-1915. PMID: 32602227, PMCID: PMC8081728, DOI: 10.1002/art.41418.Peer-Reviewed Original ResearchConceptsCGAS/STING activationExtracellular vesiclesMitochondrial DNAPattern recognition receptorsCyclic GMP-AMP synthase/stimulatorHuman lung fibroblastsSSc-ILD cohortsInterstitial lung diseaseMT-ATP6 geneΑ-SMA expressionI interferonSSc-ILDScleroderma-Associated Interstitial Lung DiseaseSynthetic CpG DNATLR-9Clinical outcomesLung diseaseSTING activationInterleukin-6Enzyme-linked immunosorbent assay-based methodProteomic profilesMulticellular originSystemic sclerosis-associated interstitial lung diseaseImmune pattern recognition receptorsExtracellular mtDNAGlucocorticoids and serum- and glucocorticoid-inducible kinase 1 are potent regulators of CFTR in the native intestine: implications for stress-induced diarrhea
Ahsan MK, Figueroa-Hall L, Baratta V, Garcia-Milian R, Lam TT, Hoque K, Salas PJ, Ameen NA. Glucocorticoids and serum- and glucocorticoid-inducible kinase 1 are potent regulators of CFTR in the native intestine: implications for stress-induced diarrhea. AJP Gastrointestinal And Liver Physiology 2020, 319: g121-g132. PMID: 32567324, PMCID: PMC7500270, DOI: 10.1152/ajpgi.00076.2020.Peer-Reviewed Original Research14-3-3 ProteinsAnimalsBacterial ToxinsCystic Fibrosis Transmembrane Conductance RegulatorDexamethasoneDiarrheaDimethyl SulfoxideEnterotoxinsEscherichia coli ProteinsGene Expression RegulationImmediate-Early ProteinsMaleNedd4 Ubiquitin Protein LigasesPhosphatidylinositol 3-KinasesProtein Serine-Threonine KinasesProtein TransportProto-Oncogene Proteins c-aktPyruvate Dehydrogenase Acetyl-Transferring KinaseRatsRats, Sprague-DawleySodium-Hydrogen Exchanger 3
2019
Identification of new biomarkers of bronchopulmonary dysplasia using metabolomics
Piersigilli F, Lam TT, Vernocchi P, Quagliariello A, Putignani L, Aghai ZH, Bhandari V. Identification of new biomarkers of bronchopulmonary dysplasia using metabolomics. Metabolomics 2019, 15: 20. PMID: 30830433, DOI: 10.1007/s11306-019-1482-9.Peer-Reviewed Original ResearchConceptsBronchopulmonary dysplasiaPreterm neonatesNew biomarkersNeonatal intensive care unitMost preterm infantsIntensive care unitNovel specific biomarkersTracheal aspirate samplesSub-group analysisGestational age differencesPreterm infantsCare unitAspirate samplesNeonatesSpecific biomarkersFirst weekC16-OHIsoleucine levelsSelect metabolitesBiomarkersDysplasiaPartial least squares discriminant analysisLeast squares discriminant analysisSquares discriminant analysisAge differences
2018
Phosphoproteomic 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 analysisQuantification of Urinary Protein Biomarkers of Autosomal Dominant Polycystic Kidney Disease by Parallel Reaction Monitoring
Rauniyar N, Yu X, Cantley J, Voss EZ, Belcher J, Colangelo CM, Stone KL, Dahl N, Parikh C, Lam TT, Cantley LG. Quantification of Urinary Protein Biomarkers of Autosomal Dominant Polycystic Kidney Disease by Parallel Reaction Monitoring. Proteomics Clinical Applications 2018, 12: e1700157. PMID: 29573172, PMCID: PMC6736530, DOI: 10.1002/prca.201700157.Peer-Reviewed Original ResearchConceptsAutosomal dominant polycystic kidney diseaseDominant polycystic kidney diseasePolycystic kidney diseaseCyst growthKidney diseaseUrinary proteinNormal controlsEnd-stage renal failureUrine samplesUrinary protein biomarkersLife-long diseasePresence of cystsRespective urine samplesMost patientsRenal failureADPKD patientsEarly diagnosisClinical relevanceUrinary proteomeParallel reaction monitoringPatientsCyst formationDiseaseWater intakePathogenesis
2017
A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease
Goffredo M, Santoro N, Tricò D, Giannini C, D’Adamo E, Zhao H, Peng G, Yu X, Lam TT, Pierpont B, Caprio S, Herzog RI. A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease. Nutrients 2017, 9: 642. PMID: 28640216, PMCID: PMC5537762, DOI: 10.3390/nu9070642.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseMagnetic resonance imagingBranched-chain amino acidsFatty liver diseaseHepatic fat contentObese adolescentsInsulin resistanceLiver diseaseTwo-step hyperinsulinemic-euglycemic clampOral glucose tolerance testSecond magnetic resonance imagingSubset of patientsGlucose tolerance testHyperinsulinemic-euglycemic clampHigher plasma levelsHepatic insulin sensitivityChain amino acidsPlasma levelsTolerance testInsulin sensitivityMetabolomic signaturePlasma metabolitesResonance imagingValine levelsLipid metabolismBrain Region and Isoform-Specific Phosphorylation Alters Kalirin SH2 Domain Interaction Sites and Calpain Sensitivity
Miller MB, Yan Y, Machida K, Kiraly DD, Levy AD, Wu YI, Lam TT, Abbott T, Koleske AJ, Eipper BA, Mains RE. Brain Region and Isoform-Specific Phosphorylation Alters Kalirin SH2 Domain Interaction Sites and Calpain Sensitivity. ACS Chemical Neuroscience 2017, 8: 1554-1569. PMID: 28418645, PMCID: PMC5517348, DOI: 10.1021/acschemneuro.7b00076.Peer-Reviewed Original ResearchConceptsLong-term potentiationCalpain sensitivityEffects of cocaineRat nucleus accumbensAdult rat nucleus accumbensRho GDP/GTP exchange factorRegion-specific effectsChronic cocaineNucleus accumbensSynaptic functionBrain regionsKALRN geneSpine morphologyPrefrontal cortexKal7CocainePotentiationFunctional significanceCalpainPhosphorylation
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 cues
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
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 experimentsPhosphataseInhibitors
2013
A Gut Lipid Messenger Links Excess Dietary Fat to Dopamine Deficiency
Tellez LA, Medina S, Han W, Ferreira JG, Licona-Limón P, Ren X, Lam TT, Schwartz GJ, de Araujo IE. A Gut Lipid Messenger Links Excess Dietary Fat to Dopamine Deficiency. Science 2013, 341: 800-802. PMID: 23950538, DOI: 10.1126/science.1239275.Peer-Reviewed Original ResearchConceptsDopamine deficiencyFed miceDietary fatExcess dietary fatBrain dopaminergic functionHigh fat intakeHigh-fat exposureGastrointestinal dysfunctionIntragastric feedingOral intakeDopaminergic functionDopamine releaseExcessive intakeIntakeMiceDeficiencyOleoylethanolamineLipid messengersPhysiological mechanismsFatMotivation deficitsLipid signalingReward sensitivityObesityDysfunction
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
2007
Posttranslational modifications on protein kinase c isozymes. Effects of epinephrine and phorbol esters
Robles-Flores M, Meléndez L, García W, Mendoza-Hernández G, Lam TT, Castañeda-Patlán C, González-Aguilar H. Posttranslational modifications on protein kinase c isozymes. Effects of epinephrine and phorbol esters. Biochimica Et Biophysica Acta 2007, 1783: 695-712. PMID: 18295358, DOI: 10.1016/j.bbamcr.2007.07.011.Peer-Reviewed Original Research