2024
Cell-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
2021
Small 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: jn-rm-0766-20. 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
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 analysis
2017
MELK Promotes Melanoma Growth by Stimulating the NF-κB Pathway
Janostiak R, Rauniyar N, Lam TT, Ou J, Zhu LJ, Green MR, Wajapeyee N. MELK Promotes Melanoma Growth by Stimulating the NF-κB Pathway. Cell Reports 2017, 21: 2829-2841. PMID: 29212029, PMCID: PMC5726781, DOI: 10.1016/j.celrep.2017.11.033.Peer-Reviewed Original ResearchConceptsMaternal embryonic leucine zipper kinaseMelanoma growthSkin cancer-related deathsMelanoma cellsNF-κB pathway activityMAPK pathwayCancer-related deathNF-κB pathwayEmbryonic leucine zipper kinaseLeucine zipper kinaseMELK knockdownCurrent therapiesMELK inhibitionImportant downstream mediatorShort-term benefitsPharmacological inhibitionTranscription factor E2F1Downstream mediatorBRAFV600E inhibitorsSequestosome 1Pathway activityMELK functionMediatorsCell culturesInhibition
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
2014
Angiotensin II signaling via protein kinase C phosphorylates Kelch-like 3, preventing WNK4 degradation
Shibata S, Arroyo JP, Castañeda-Bueno M, Puthumana J, Zhang J, Uchida S, Stone KL, Lam TT, Lifton RP. Angiotensin II signaling via protein kinase C phosphorylates Kelch-like 3, preventing WNK4 degradation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 15556-15561. PMID: 25313067, PMCID: PMC4217463, DOI: 10.1073/pnas.1418342111.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceAngiotensin IIAnimalsCarrier ProteinsCell LineHumansKidneyMice, Inbred C57BLMicrofilament ProteinsMolecular Sequence DataPhosphorylationPhosphoserineProtein BindingProtein Kinase CProtein Serine-Threonine KinasesProteolysisSignal TransductionConceptsRenal salt reabsorptionAngiotensin IIVolume depletionSalt reabsorptionNormal physiologic responseProtein kinase CAII administrationBlood pressureCardiovascular diseaseGlobal burdenPhysiologic responsesCullin 3Kinase CNaCl cotransporterReabsorptionHuman genetic studiesSecretionHypertensionNormal mechanismsWNK4 degradationMissense mutationsSerine 433WNK4Inverse relationshipCultured cells
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