Featured Publications
An optogenetic-phosphoproteomic study reveals dynamic Akt1 signaling profiles in endothelial cells
Zhou W, Li W, Wang S, Salovska B, Hu Z, Tao B, Di Y, Punyamurtula U, Turk B, Sessa W, Liu Y. An optogenetic-phosphoproteomic study reveals dynamic Akt1 signaling profiles in endothelial cells. Nature Communications 2023, 14: 3803. PMID: 37365174, PMCID: PMC10293293, DOI: 10.1038/s41467-023-39514-1.Peer-Reviewed Original ResearchConceptsPhosphorylation sitesSerine/threonine kinase AktMass spectrometry-based phosphoproteomicsThreonine kinase AktAkt-dependent phosphorylationAberrant Akt activationEndothelial cellsKinase substrateKinase AktCell signalingPhosphorylation profilePhenotypic outcomesDownstream signalingAkt activationAkt1 phosphorylationHuman diseasesSystem-level analysisAKT1Vascular endothelial cellsRich resourcePhosphorylationSignalingGrowth factorAktCellsPhosphoproteomic analysis of metformin signaling in colorectal cancer cells elucidates mechanism of action and potential therapeutic opportunities
Salovska B, Gao E, Müller‐Dott S, Li W, Cordon C, Wang S, Dugourd A, Rosenberger G, Saez‐Rodriguez J, Liu Y. Phosphoproteomic analysis of metformin signaling in colorectal cancer cells elucidates mechanism of action and potential therapeutic opportunities. Clinical And Translational Medicine 2023, 13: e1179. PMID: 36781298, PMCID: PMC9925373, DOI: 10.1002/ctm2.1179.Peer-Reviewed Original ResearchConceptsColorectal cancerLong-term metformin treatmentType 2 diabetesCRC cell linesColorectal cancer cellsBiguanide drug metforminPotential therapeutic opportunitiesMechanism of actionPharmacodynamic interactionsMetformin treatmentTreatment of cancerCRC cellsCell proliferation assaysClinical trialsBcl-2/Bcl-xL inhibitorMetforminDrug metforminTherapeutic opportunitiesProliferation assaysCancer cellsPotential cancer therapeuticsPotential roleExpression levelsCell linesCancer therapeuticsProteotype coevolution and quantitative diversity across 11 mammalian species
Ba Q, Hei Y, Dighe A, Li W, Maziarz J, Pak I, Wang S, Wagner GP, Liu Y. Proteotype coevolution and quantitative diversity across 11 mammalian species. Science Advances 2022, 8: eabn0756. PMID: 36083897, PMCID: PMC9462687, DOI: 10.1126/sciadv.abn0756.Peer-Reviewed Original ResearchConceptsMammalian speciesRNA metabolic processesCommon mammalian speciesUbiquitin-proteasome systemEvolutionary profilingMammalian lineagesProteomic methodsProtein degradationProtein abundanceGene expressionProtein expression levelsHigh interspeciesMetabolic processesCovariation analysisFunctional roleNucleotide levelExpression levelsQuantitative diversityCoevolutionMammalsSpeciesRemarkable variationExpressionTranscriptomeBiological variabilityGlobal and Site-Specific Effect of Phosphorylation on Protein Turnover
Wu C, Ba Q, Lu D, Li W, Salovska B, Hou P, Mueller T, Rosenberger G, Gao E, Di Y, Zhou H, Fornasiero EF, Liu Y. Global and Site-Specific Effect of Phosphorylation on Protein Turnover. Developmental Cell 2020, 56: 111-124.e6. PMID: 33238149, PMCID: PMC7855865, DOI: 10.1016/j.devcel.2020.10.025.Peer-Reviewed Original ResearchConceptsProtein turnoverProtein lifetimeCyclin-dependent kinase substrateStable isotope-labeled amino acidsSite-specific phosphorylationPulse-labeling approachIsotope-labeled amino acidsMass spectrometry-based methodCell fitnessKinase substratePhosphorylation sitesPhosphorylated sitesProteomic methodsCell signalingSpectrometry-based methodsLive cellsAmino acidsPhosphositesRich resourceDisease biologyLabeling approachPhosphorylationModification typesGlutamic acidTurnoverOncogene-like addiction to aneuploidy in human cancers
Girish V, Lakhani A, Thompson S, Scaduto C, Brown L, Hagenson R, Sausville E, Mendelson B, Kandikuppa P, Lukow D, Yuan M, Stevens E, Lee S, Schukken K, Akalu S, Vasudevan A, Zou C, Salovska B, Li W, Smith J, Taylor A, Martienssen R, Liu Y, Sun R, Sheltzer J. Oncogene-like addiction to aneuploidy in human cancers. Science 2023, 381: eadg4521. PMID: 37410869, PMCID: PMC10753973, DOI: 10.1126/science.adg4521.Peer-Reviewed Original ResearchMulti-omic measurements of heterogeneity in HeLa cells across laboratories
Liu Y, Mi Y, Mueller T, Kreibich S, Williams EG, Van Drogen A, Borel C, Frank M, Germain PL, Bludau I, Mehnert M, Seifert M, Emmenlauer M, Sorg I, Bezrukov F, Bena FS, Zhou H, Dehio C, Testa G, Saez-Rodriguez J, Antonarakis SE, Hardt WD, Aebersold R. Multi-omic measurements of heterogeneity in HeLa cells across laboratories. Nature Biotechnology 2019, 37: 314-322. PMID: 30778230, DOI: 10.1038/s41587-019-0037-y.Peer-Reviewed Original ResearchConceptsCell linesGenome-wide copy numberMulti-omic measurementsHuman cultured cellsProtein turnover ratesPhenotypic responsesGenomic variabilityDifferent cell linesHeLa variantsSpecific cell linesCopy numberHeLa cellsCultured cellsHeLa cell linePhenotypic variabilityProgressive divergenceTurnover rateCellsBiological variationTechnical variationUniform conditionsTranscriptomeProteomeSuccessive passagesLinesProteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies.
Liu Q, Zhang J, Guo C, Wang M, Wang C, Yan Y, Sun L, Wang D, Zhang L, Yu H, Hou L, Wu C, Zhu Y, Jiang G, Zhu H, Zhou Y, Fang S, Zhang T, Hu L, Li J, Liu Y, Zhang H, Zhang B, Ding L, Robles AI, Rodriguez H, Gao D, Ji H, Zhou H, Zhang P. Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies. Cell 2024, 187: 184-203.e28. PMID: 38181741, DOI: 10.1016/j.cell.2023.12.004.Peer-Reviewed Original Research
2024
PTMoreR-enabled cross-species PTM mapping and comparative phosphoproteomics across mammals
Wang S, Di Y, Yang Y, Salovska B, Li W, Hu L, Yin J, Shao W, Zhou D, Cheng J, Liu D, Yang H, Liu Y. PTMoreR-enabled cross-species PTM mapping and comparative phosphoproteomics across mammals. Cell Reports Methods 2024, 4: 100859. PMID: 39255793, PMCID: PMC11440062, DOI: 10.1016/j.crmeth.2024.100859.Peer-Reviewed Original ResearchConceptsP-siteSurrounding amino acid sequenceKinase-substrate networkQuantitative phosphoproteomic analysisFunctional enrichment analysisPhosphoproteomic resultsKinase motifsComparative phosphoproteomicsPTM sitesPhosphorylation eventsPhosphoproteomic analysisProteomic analysisEnrichment analysisMammalian speciesSpeciesEvolutionary anglePhosphoproteomeMotifEnvironmental factorsNon-human speciesPTMProteomicsKinaseMammalsProteinMultiscale modeling uncovers 7q11.23 copy number variation–dependent changes in ribosomal biogenesis and neuronal maturation and excitability
Mihailovich M, Germain P, Shyti R, Pozzi D, Noberini R, Liu Y, Aprile D, Tenderini E, Troglio F, Trattaro S, Fabris S, Ciptasari U, Rigoli M, Caporale N, D’Agostino G, Mirabella F, Vitriolo A, Capocefalo D, Skaros A, Franchini A, Ricciardi S, Biunno I, Neri A, Kasri N, Bonaldi T, Aebersold R, Matteoli M, Testa G. Multiscale modeling uncovers 7q11.23 copy number variation–dependent changes in ribosomal biogenesis and neuronal maturation and excitability. Journal Of Clinical Investigation 2024, 134: e168982. PMID: 39007270, PMCID: PMC11245157, DOI: 10.1172/jci168982.Peer-Reviewed Original ResearchConceptsCopy number variationsWilliams-Beuren syndromeRibosome biogenesisP-RPS6Neurodevelopmental disordersRibosomal genesP-4EBPNumber variationsTranslation factorsMicroduplication syndromeMolecular mechanismsGenesNeuronal differentiationPatient-derivedIntrinsic excitabilityMTOR pathwayBiogenesisNeuronal maturationPhosphorylated rpS6Neuronal transmissionWilliams-BeurenPathophysiological relevanceNeurocognitive featuresIntellectual disabilityDisease modelsNetwork-based elucidation of colon cancer drug resistance mechanisms by phosphoproteomic time-series analysis
Rosenberger G, Li W, Turunen M, He J, Subramaniam P, Pampou S, Griffin A, Karan C, Kerwin P, Murray D, Honig B, Liu Y, Califano A. Network-based elucidation of colon cancer drug resistance mechanisms by phosphoproteomic time-series analysis. Nature Communications 2024, 15: 3909. PMID: 38724493, PMCID: PMC11082183, DOI: 10.1038/s41467-024-47957-3.Peer-Reviewed Original ResearchConceptsMechanism of cell responseResistance mechanismsSignaling pathway responsesDrug resistance mechanismsEnzyme/substrate interactionsAdaptive resistance mechanismsNetwork rewiringPhosphorylation stateSignaling pathway activationDrug perturbationsProteomic technologiesSignaling crosstalkPathway responsesInhibitor designPathway activationCancer drug resistance mechanismsCell adaptive responsesAdaptive responsePhosphatase activityNetwork-based methodologyRewiringTherapeutic efficacyPhosphoproteome coverageCell responsesControl mediumFibroblast expression of transmembrane protein smoothened governs microenvironment characteristics after acute kidney injury
Gui Y, Fu H, Palanza Z, Tao J, Lin Y, Min W, Qiao Y, Bonin C, Hargis G, Wang Y, Yang P, Kreutzer D, Wang Y, Liu Y, Yu Y, Liu Y, Zhou D. Fibroblast expression of transmembrane protein smoothened governs microenvironment characteristics after acute kidney injury. Journal Of Clinical Investigation 2024, 134: e165836. PMID: 38713523, PMCID: PMC11213467, DOI: 10.1172/jci165836.Peer-Reviewed Original ResearchNidogen-1Expression of transmembrane proteinsCell-matrix interactionsAcute kidney injuryExtracellular matrix proteinsWnt signaling pathwayGlobal proteomeHedgehog signalingTransmembrane proteinsTubular cell apoptosisSignaling pathwayCell apoptosisMatrix proteinsIntegrin B1Kidney fibroblastsMesenchymal cell activationKidney injuryHedgehogProteinMitigate acute kidney injurySMOPreserved kidney functionAcute kidney injury pathogenesisFibroblastsPhosphoproteomeReciprocal antagonism of PIN1-APC/C(CDH1) governs mitotic protein stability and cell cycle entry.
Ke S, Dang F, Wang L, Chen JY, Naik MT, Li W, Thavamani A, Kim N, Naik NM, Sui H, Tang W, Qiu C, Koikawa K, Batalini F, Stern Gatof E, Isaza DA, Patel JM, Wang X, Clohessy JG, Heng YJ, Lahav G, Liu Y, Gray NS, Zhou XZ, Wei W, Wulf GM, Lu KP. Reciprocal antagonism of PIN1-APC/C(CDH1) governs mitotic protein stability and cell cycle entry. Nat Commun 2024, 15: 3220. PMID: 38622115, DOI: 10.1038/s41467-024-47427-w.Peer-Reviewed Original ResearchEGFR targeting PhosTACs as a dual inhibitory approach reveals differential downstream signaling
Hu Z, Chen P, Li W, Krone M, Zheng S, Saarbach J, Velasco I, Hines J, Liu Y, Crews C. EGFR targeting PhosTACs as a dual inhibitory approach reveals differential downstream signaling. Science Advances 2024, 10: eadj7251. PMID: 38536914, PMCID: PMC10971414, DOI: 10.1126/sciadv.adj7251.Peer-Reviewed Original ResearchConceptsInhibit cancer cell viabilityProteome-wide levelCancer cell viabilityDifferential signaling pathwaysPhosphoproteomic approachTyrosine dephosphorylationProtein dephosphorylationSignal transductionActivating dephosphorylationInduce apoptosisReceptor tyrosine kinase inhibitorsRTK activationSignaling pathwayInhibition of kinasesDephosphorylationEpidermal growth factor receptorGrowth factor receptorCell viabilityFactor receptorInhibitory approachesTyrosineTyrosine kinase inhibitorsInhibitory effectInhibitory potentialKinase inhibitorsWnt5 controls splenic myelopoiesis and neutrophil functional ambivalency during DSS-induced colitis
Luan Y, Hu J, Wang Q, Wang X, Li W, Qu R, Yang C, Rajendran B, Zhou H, Liu P, Zhang N, Shi Y, Liu Y, Tang W, Lu J, Wu D. Wnt5 controls splenic myelopoiesis and neutrophil functional ambivalency during DSS-induced colitis. Cell Reports 2024, 43: 113934. PMID: 38461416, PMCID: PMC11064424, DOI: 10.1016/j.celrep.2024.113934.Peer-Reviewed Original ResearchCD8<sup>+</sup> T cell activationNeutrophil productionNeutrophil plasticitySplenic extramedullary myelopoiesisFamily member 5T cell activationInnate immune cellsSplenic stromal cellsDSS-induced colitisAnti-inflammatory protectionCD101 expressionPro-inflammatory activitySplenic myelopoiesisExtramedullary myelopoiesisBone marrowImmune cellsSplenic neutrophilsMember 5Autoimmune diseasesInflammatory outcomesCell activationStromal cellsColitisSplenic productionElevated numbersMeeting Report on the 3rd Chinese American Society for Mass Spectrometry Conference-Advancing Biological and Pharmaceutical Mass Spectrometry.
Chen H, Fu Y, Han M, Han X, Hao L, Huan T, Huang L, Huang M, Ji Q, Jiang T, Jiang Y, Li L, Li L, Liang X, Lih M, Lin Y, Liu X, Liu T, Liu Y, Ma S, Peng J, Qi YA, Qu J, Shou W, Sun L, Wang M, Wang S, Wu R, Wu S, Yan X, Yang J, Yang W, Yang Z, Yu Y, Zhang H, Zhang H, Zhao S, Zhu J, Zhu Y, Wang Y, Weng N. Meeting Report on the 3rd Chinese American Society for Mass Spectrometry Conference-Advancing Biological and Pharmaceutical Mass Spectrometry. Biomed Chromatogr 2024, 38: e5795. PMID: 38071756, DOI: 10.1002/bmc.5795.Peer-Reviewed Original ResearchThe CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells
Liao X, Li W, Zhou H, Rajendran B, Li A, Ren J, Luan Y, Calderwood D, Turk B, Tang W, Liu Y, Wu D. The CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells. Nature Communications 2024, 15: 603. PMID: 38242867, PMCID: PMC10798966, DOI: 10.1038/s41467-024-44885-0.Peer-Reviewed Original ResearchConceptsCD8+ T cellsT cellsCancer immunotherapyMouse CD8+ T cellsAnti-tumor immunityTumor growth inhibition abilityAnti-tumor effectsInhibition of neddylationCD8Effector functionsTCR stimulationIL2 signalingCentral signaling pathwaysCore signaling pathwaysEffector activityNegative regulatory mechanismsTranslational implicationsImmunotherapyGrowth inhibition abilityCytokine signalingTCRProteomic alterationsSignaling pathwayCancerCRISPR-based screens
2023
The SysteMHC Atlas v2.0, an updated resource for mass spectrometry-based immunopeptidomics
Huang X, Gan Z, Cui H, Lan T, Liu Y, Caron E, Shao W. The SysteMHC Atlas v2.0, an updated resource for mass spectrometry-based immunopeptidomics. Nucleic Acids Research 2023, 52: d1062-d1071. PMID: 38000392, PMCID: PMC10767952, DOI: 10.1093/nar/gkad1068.Peer-Reviewed Original ResearchCalponin 2 regulates ketogenesis to mitigate acute kidney injury
Gui Y, Palanza Z, Gupta P, Li H, Pan Y, Wang Y, Hargis G, Kreutzer D, Wang Y, Bastacky S, Liu Y, Liu S, Zhou D. Calponin 2 regulates ketogenesis to mitigate acute kidney injury. JCI Insight 2023, 8: e170521. PMID: 37751293, PMCID: PMC10721266, DOI: 10.1172/jci.insight.170521.Peer-Reviewed Original ResearchConceptsAcute kidney injuryEstrogen receptor 2Fatty acid oxidationKidney injuryKidney fibrosisCalponin 2Ketone body β-hydroxybutyrateTubular cell deathBody β-hydroxybutyrateSirtuin 5Endogenous ketogenesisKidney functionReceptor 2Protein posttranslational modificationsRate-limiting enzymeFAO pathwayMitochondrial sirtuin 5Animal kidneysΒ-hydroxybutyrateOrgan performanceCell proliferationSynthase 2FibrosisPosttranslational modificationsInjuryA fully automated FAIMS-DIA mass spectrometry-based proteomic pipeline.
Reilly L, Lara E, Ramos D, Li Z, Pantazis CB, Stadler J, Santiana M, Roberts J, Faghri F, Hao Y, Nalls MA, Narayan P, Liu Y, Singleton AB, Cookson MR, Ward ME, Qi YA. A fully automated FAIMS-DIA mass spectrometry-based proteomic pipeline. Cell Rep Methods 2023, 100593. PMID: 37729920, DOI: 10.1016/j.crmeth.2023.100593.Peer-Reviewed Original Research7SK methylation by METTL3 promotes transcriptional activity
Perez-Pepe M, Desotell A, Li H, Li W, Han B, Lin Q, Klein D, Liu Y, Goodarzi H, Alarcón C. 7SK methylation by METTL3 promotes transcriptional activity. Science Advances 2023, 9: eade7500. PMID: 37163588, PMCID: PMC10171809, DOI: 10.1126/sciadv.ade7500.Peer-Reviewed Original ResearchConceptsTranscriptional elongationTranscriptional responseAdaptive transcriptional responseHeterogeneous nuclear ribonucleoproteinsElongation factor complexPositive transcription elongation factor complexGrowth factorExtracellular signalsRNA modificationsRNA 7SKEpidermal growth factorCell signalingInduces phosphorylationMethyltransferase 3Nuclear ribonucleoproteinFactor complexTranscriptional activityUnknown functionMethylationMETTL3RibonucleoproteinPhosphorylationTEFbElongationSignaling