2024
Proteomic 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 communicationCellular stiffness sensing through talin 1 in tissue mechanical homeostasis
Chanduri M, Kumar A, Weiss D, Emuna N, Barsukov I, Shi M, Tanaka K, Wang X, Datye A, Kanyo J, Collin F, Lam T, Schwarz U, Bai S, Nottoli T, Goult B, Humphrey J, Schwartz M. Cellular stiffness sensing through talin 1 in tissue mechanical homeostasis. Science Advances 2024, 10: eadi6286. PMID: 39167642, PMCID: PMC11338229, DOI: 10.1126/sciadv.adi6286.Peer-Reviewed Original ResearchConceptsTissue mechanical homeostasisStiffness sensingExtracellular matrixTalin-1Mechanical homeostasisExtracellular matrix mechanicsIncreased cell spreadingCell spreadingTalinMutationsCellular sensingFibrillar collagenReduced axial stiffnessTissue mechanical propertiesMechanical propertiesAxial stiffnessCompliant substratesHomeostasisRupture pressureArp2/3ARPC5LStiffnessHomeostasis hypothesisResident cellsTissue stiffnessA complex of the lipid transport ER proteins TMEM24 and C2CD2 with band 4.1 at cell–cell contacts
Johnson B, Iuliano M, Lam T, Biederer T, De Camilli P. A complex of the lipid transport ER proteins TMEM24 and C2CD2 with band 4.1 at cell–cell contacts. Journal Of Cell Biology 2024, 223: e202311137. PMID: 39158698, PMCID: PMC11334333, DOI: 10.1083/jcb.202311137.Peer-Reviewed Original ResearchConceptsPlasma membraneNon-vesicular lipid transferSites of cell contactC-terminus motifsCell contact-dependent signalsContact-dependent signalingCell-cell contactER/PM junctionsTMEM24ER proteinsPM proteinsSynCAM 1Cell adhesion moleculesCellular functionsLipid transferC2CD2Phospholipid transportLipid transportCell contactProteinAdhesion moleculesCalcium homeostasisCellsFamily membersParalogsCell-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
DOT1L bridges transcription and heterochromatin formation at mammalian pericentromeres
Malla A, Yu H, Farris D, Kadimi S, Lam T, Cox A, Smith Z, Lesch B. DOT1L bridges transcription and heterochromatin formation at mammalian pericentromeres. EMBO Reports 2023, 24: e56492. PMID: 37317657, PMCID: PMC10398668, DOI: 10.15252/embr.202256492.Peer-Reviewed Original ResearchConceptsMouse embryonic stem cellsBurst of transcriptionMajor satellite repeatsLong-term silencingRepetitive DNA elementsEmbryonic stem cellsSatellite transcriptionHeterochromatin stabilityHeterochromatin formationHeterochromatin structureChromatin stateSatellite repeatsGenome stabilityGenome integrityPericentromeric repeatsPericentromeric heterochromatinGenome featuresDNA elementsHistone H3Transcriptional activationHistone methyltransferaseRepetitive elementsDOT1L lossRepeat elementsTranscript productionDifferential Effects of Cocaine and Morphine on the Diurnal Regulation of the Mouse Nucleus Accumbens Proteome
Ketchesin K, Becker-Krail D, Xue X, Wilson R, Lam T, Williams K, Nairn A, Tseng G, Logan R. Differential Effects of Cocaine and Morphine on the Diurnal Regulation of the Mouse Nucleus Accumbens Proteome. Journal Of Proteome Research 2023, 22: 2377-2390. PMID: 37311105, PMCID: PMC10392613, DOI: 10.1021/acs.jproteome.3c00126.Peer-Reviewed Original ResearchConceptsNucleus accumbensDiurnal regulationMouse nucleus accumbensPhase-dependent regulationBrain regionsDiurnal rhythmAdministration of psychostimulantsEffects of cocaineSubstance use disordersDifferential effectsMolecular rhythmsProtein rhythmsQuantitative proteomicsProteomic dataProteomeMorphine administrationUse of substancesRhythm alterationsGlucocorticoid signalingUse disordersMorphineSubstance useProtein expressionCocaineSignificant alterationsThe C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion
Onuchic L, Padovano V, Schena G, Rajendran V, Dong K, Shi X, Pandya R, Rai V, Gresko N, Ahmed O, Lam T, Wang W, Shen H, Somlo S, Caplan M. The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion. Nature Communications 2023, 14: 1790. PMID: 36997516, PMCID: PMC10063565, DOI: 10.1038/s41467-023-37449-1.Peer-Reviewed Original ResearchConceptsPolycystin-1Nicotinamide nucleotide transhydrogenaseTerminal tailCystic phenotypeAutosomal dominant polycystic kidney diseaseCyst cell proliferationC-terminal domainAmino acid residuesLethal monogenic disorderC-terminal cleavageNucleotide transhydrogenaseAcid residuesMitochondrial functionTransgenic expressionPKD1 geneRedox stateShort fragmentsCell proliferationMonogenic disordersDominant polycystic kidney diseasePolycystic kidney diseaseGene therapy strategiesProteinPhenotypeFragmentsDopamine 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
Carbonyl Posttranslational Modification Associated With Early-Onset Type 1 Diabetes Autoimmunity.
Yang ML, Connolly SE, Gee RJ, Lam TT, Kanyo J, Peng J, Guyer P, Syed F, Tse HM, Clarke SG, Clarke CF, James EA, Speake C, Evans-Molina C, Arvan P, Herold KC, Wen L, Mamula MJ. Carbonyl Posttranslational Modification Associated With Early-Onset Type 1 Diabetes Autoimmunity. Diabetes 2022, 71: 1979-1993. PMID: 35730902, PMCID: PMC9450849, DOI: 10.2337/db21-0989.Peer-Reviewed Original ResearchConceptsType 1 diabetesNOD miceMurine type 1 diabetesHuman type 1 diabetesDecreased glucose-stimulated insulin secretionAnti-insulin autoimmunityPrediabetic NOD miceGlucose-stimulated insulin secretionOnset Type 1T cell responsesOnset of hyperglycemiaCirculation of patientsAutoreactive CD4Insulin ratioInsulin secretionDiabetesPancreatic isletsType 1Islet proteinsOxidative stressAutoimmunitySelect groupMiceCarbonyl modificationOnsetCitrullination of glucokinase is linked to autoimmune diabetes
Yang ML, Horstman S, Gee R, Guyer P, Lam TT, Kanyo J, Perdigoto AL, Speake C, Greenbaum CJ, Callebaut A, Overbergh L, Kibbey RG, Herold KC, James EA, Mamula MJ. Citrullination of glucokinase is linked to autoimmune diabetes. Nature Communications 2022, 13: 1870. PMID: 35388005, PMCID: PMC8986778, DOI: 10.1038/s41467-022-29512-0.Peer-Reviewed Original ResearchConceptsGlucose-stimulated insulin secretionResult of inflammationType 1 diabetesBeta-cell metabolismPancreatic beta cellsAutoimmune diabetesNOD miceAutoreactive CD4Inflammatory cytokinesAutoimmune biomarkersInsulin secretionT cellsBeta cellsType 1InflammationBiologic activityReactive oxygen speciesDiabetesPost-translational modificationsDiabetes biomarkersGlycogen synthesisBiomarkersCitrullinationGlucokinaseOxygen speciesIdentification 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 functionSex- 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 signaturePneumoniaCocaine 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 releaseItaconate is an effector of a Rab GTPase cell-autonomous host defense pathway against Salmonella
Chen M, Sun H, Boot M, Shao L, Chang SJ, Wang W, Lam TT, Lara-Tejero M, Rego EH, Galán JE. Itaconate is an effector of a Rab GTPase cell-autonomous host defense pathway against Salmonella. Science 2020, 369: 450-455. PMID: 32703879, PMCID: PMC8020367, DOI: 10.1126/science.aaz1333.Peer-Reviewed Original ResearchGlucocorticoids 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
Synovial fluid proteome changes in ACL injury-induced posttraumatic osteoarthritis: Proteomics analysis of porcine knee synovial fluid
Kiapour AM, Sieker JT, Proffen BL, Lam TT, Fleming BC, Murray MM. Synovial fluid proteome changes in ACL injury-induced posttraumatic osteoarthritis: Proteomics analysis of porcine knee synovial fluid. PLOS ONE 2019, 14: e0212662. PMID: 30822327, PMCID: PMC6396923, DOI: 10.1371/journal.pone.0212662.Peer-Reviewed Original Research
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