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 vulnerabilityA fluorescence-based assay for measuring polyamine biosynthesis aminopropyl transferase–mediated catalysis
Singh P, Choi J, Wang W, T Lam T, Lechner P, Vanderwal C, Pou S, Nilsen A, Ben Mamoun C. A fluorescence-based assay for measuring polyamine biosynthesis aminopropyl transferase–mediated catalysis. Journal Of Biological Chemistry 2024, 300: 107832. PMID: 39342998, DOI: 10.1016/j.jbc.2024.107832.Peer-Reviewed Original ResearchAminopropyl transferaseFluorescence-based assayLack of high-throughput assaysHigh-throughput screeningCarbon chain lengthChemical librariesMass spectrometryChain lengthHigh-throughput assayDrug discoveryMass spectrometry analysisSaccharomyces cerevisiaeThin-layer chromatographyFluorescence intensityCellular functionsSpectrometry analysisPolycationic moleculesFluorescent conjugatesIsoindoleAPT activityCatalysisAssayBenzeneAdductsEnzymeProteomic 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 knockdownGlioblastomaPhosphorylation of the nuclear poly(A) binding protein (PABPN1) during mitosis protects mRNA from hyperadenylation and maintains transcriptome dynamics
Gordon J, Phizicky D, Schärfen L, Brown C, Escayola D, Kanyo J, Lam T, Simon M, Neugebauer K. Phosphorylation of the nuclear poly(A) binding protein (PABPN1) during mitosis protects mRNA from hyperadenylation and maintains transcriptome dynamics. Nucleic Acids Research 2024, 52: 9886-9903. PMID: 38943343, PMCID: PMC11381358, DOI: 10.1093/nar/gkae562.Peer-Reviewed Original ResearchPoly(A)-binding proteinTranscriptome dynamicsNuclear poly(A) binding proteinPoly(A) binding proteinMode of gene regulationFunctional consequences of phosphorylationLong-read sequencingIncreased mRNA turnoverNucleo-cytoplasmic exportConsequences of phosphorylationRegulation of poly(ACohort of mRNAsGene expression programsMRNA biogenesisCytoplasmic mixingMRNA turnoverGene regulationShorter poly(ARNA stabilityMitotic kinasesPoly(ACell cycleMRNA synthesisIncreased transcriptionBinding proteinBERNN: Enhancing classification of Liquid Chromatography Mass Spectrometry data with batch effect removal neural networks
Pelletier S, Leclercq M, Roux-Dalvai F, de Geus M, Leslie S, Wang W, Lam T, Nairn A, Arnold S, Carlyle B, Precioso F, Droit A. BERNN: Enhancing classification of Liquid Chromatography Mass Spectrometry data with batch effect removal neural networks. Nature Communications 2024, 15: 3777. PMID: 38710683, PMCID: PMC11074280, DOI: 10.1038/s41467-024-48177-5.Peer-Reviewed Original ResearchConceptsLC-MS experimentsLC-MSLiquid chromatography mass spectrometry dataComplex biological samplesMass spectrometry dataLiquid chromatography mass spectrometryChromatography mass spectrometryMass spectrometrySpectrometry dataEffective removalBiological samplesExperimental conditionsBatch effect removalSample processing protocolBatch effectsSpectrometryBatch effect correction methodsCorrecting batch effectsRemoval of batch effectsOptimal conditions for carrying out trypsin digestions on complex proteomes: From bulk samples to single cells
Mansuri M, Bathla S, Lam T, Nairn A, Williams K. Optimal conditions for carrying out trypsin digestions on complex proteomes: From bulk samples to single cells. Journal Of Proteomics 2024, 297: 105109. PMID: 38325732, PMCID: PMC10939724, DOI: 10.1016/j.jprot.2024.105109.Peer-Reviewed Original ResearchComplex proteomesProtein cleavage activityOptimal conditionsTrypsin digestion protocolReversed phase HPLC separationMass spectrometry workflowMS-based proteomicsMass spectrometric analysisC-terminal amino acid residuesTrypsin digestionChromatographic separationDigestion protocolAmino acid residuesHPLC separationMS/MS analysisGlobal proteomic analysisSingle cellsSample matrixSpectrometric analysisCleavage specificityGeneration of peptidesAcid residuesDown proteinsProteomic analysisCleavage activity
2023
Dual regulation of SLC25A39 by AFG3L2 and iron controls mitochondrial glutathione homeostasis
Shi X, DeCiucis M, Grabinska K, Kanyo J, Liu A, Lam T, Shen H. Dual regulation of SLC25A39 by AFG3L2 and iron controls mitochondrial glutathione homeostasis. Molecular Cell 2023, 84: 802-810.e6. PMID: 38157846, PMCID: PMC10922821, DOI: 10.1016/j.molcel.2023.12.008.Peer-Reviewed Original ResearchProtein quality controlMitochondrial protein quality controlDual regulationMetabolic compartmentalizationIron homeostasisMitochondrial iron-sulfur clustersIron-sulfur clustersMitochondrial transportersProtein regulationMammalian cellsCRISPR knockoutCysteine residuesTransporter regulationLoop 1SLC25A39Glutathione homeostasisMetabolic sensingGlutathione uptakeMature neuronsProtein levelsHomeostasisRegulationAFG3L2Biochemical featuresMitochondrial glutathione levelsMass spectrometry on cerebrospinal fluid uncovers association of novel glycolysis biomarkers with Alzheimer’s disease in a complex clinical cohort
de Geus M, Leslie S, Wang W, Lam T, Broekman M, Neefjes S, Nairn A, Carlyle B, Arnold S. Mass spectrometry on cerebrospinal fluid uncovers association of novel glycolysis biomarkers with Alzheimer’s disease in a complex clinical cohort. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.078466.Peer-Reviewed Original ResearchAlzheimer's diseaseMild cognitive impairmentHospital neurology serviceNon-AD diagnosesDiagnostic lumbar puncturePrognosis of ADCerebrospinal fluid biomarkersClinic cohortFurther mechanistic studiesNeurology serviceFDG-PETBrain metabolismFluid biomarkersLumbar puncturePatient cohortClinical indicationsDisease progressionATN biomarkersClinical cohortTreatment responseComplex cohortBackground DiagnosisCSF samplesTreatment efficacyLinear regression analysisMicrobiome Depletion Increases Fentanyl Self-Administration and Alters the Striatal Proteome Through Short-Chain Fatty Acids
Hofford R, Meckel K, Wiser E, Wang W, Sens J, Kim M, Godino A, Lam T, Kiraly D. Microbiome Depletion Increases Fentanyl Self-Administration and Alters the Striatal Proteome Through Short-Chain Fatty Acids. ENeuro 2023, 11: eneuro.0388-23.2023. PMID: 38164564, PMCID: PMC10875718, DOI: 10.1523/eneuro.0388-23.2023.Peer-Reviewed Original ResearchMass spectrometry in cerebrospinal fluid uncovers association of glycolysis biomarkers with Alzheimer’s disease in a large clinical sample
de Geus M, Leslie S, Lam T, Wang W, Roux-Dalvai F, Droit A, Kivisakk P, Nairn A, Arnold S, Carlyle B. Mass spectrometry in cerebrospinal fluid uncovers association of glycolysis biomarkers with Alzheimer’s disease in a large clinical sample. Scientific Reports 2023, 13: 22406. PMID: 38104170, PMCID: PMC10725469, DOI: 10.1038/s41598-023-49440-3.Peer-Reviewed Original ResearchCommon 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 studiesEpilepsyNatural isoaspartyl protein modification of ZAP70 alters T cell responses in lupus
Yang M, Lam T, Kanyo J, Kang I, Zhou Z, Clarke S, Mamula M. Natural isoaspartyl protein modification of ZAP70 alters T cell responses in lupus. Autoimmunity 2023, 56: 2282945. PMID: 37994408, PMCID: PMC10897934, DOI: 10.1080/08916934.2023.2282945.Peer-Reviewed Original ResearchMulti-omics profiling reveals cellular pathways and functions regulated by ALDH1B1 in colon cancer cells
Wang Y, Popovic Z, Charkoftaki G, Garcia-Milian R, Lam T, Thompson D, Chen Y, Vasiliou V. Multi-omics profiling reveals cellular pathways and functions regulated by ALDH1B1 in colon cancer cells. Chemico-Biological Interactions 2023, 384: 110714. PMID: 37716420, PMCID: PMC10807983, DOI: 10.1016/j.cbi.2023.110714.Peer-Reviewed Original ResearchColon cancer cellsCellular stress response pathwaysStress response pathwaysMulti-omics analysisCancer cellsSecond messenger signalingMulti-omics profilingNew molecular informationFunctional annotationCellular functionsResponse pathwaysKinase signalingCellular pathwaysColon adenocarcinoma cell lineHuman colon adenocarcinoma cell lineApoptosis signalingEnrichment analysisAldehyde dehydrogenase 1B1Molecular signaturesAdenocarcinoma cell lineMolecular informationSignalingNovel targetProtein expressionCell linesDOT1L 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 alterationsBiomarkers as prognostic determinants of epilepsy after post-acute central nervous system insults: a systematic review and meta-analysis (P3-5.017)
Misra S, Khan E, Lam T, Mazumder R, Eldem E, Gururangan K, Hickman L, Goswami V, Funaro M, Montaner J, Quinn T, Liebeskind D, Mishra N. Biomarkers as prognostic determinants of epilepsy after post-acute central nervous system insults: a systematic review and meta-analysis (P3-5.017). Neurology 2023, 100 DOI: 10.1212/wnl.0000000000203165.Peer-Reviewed Original ResearchPeripheral 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 study