Wenxue Li
Associate Research Scientist in PharmacologyCards
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Research
Publications
2025
Matrix Stiffness Directs Early Injury and Ketogenesis Programs to Prime Kidney Repair
Gui Y, Wang Y, Li W, Liu J, Zheng K, Li J, Shaffer H, Jones C, Mallari S, Yu Y, Liu S, Liu Y, Zhou D. Matrix Stiffness Directs Early Injury and Ketogenesis Programs to Prime Kidney Repair. Journal Of The American Society Of Nephrology 2025 DOI: 10.1681/asn.0000000967.Peer-Reviewed Original ResearchExtracellular matrixMatrisome componentsHippo pathway kinasesIntegrin receptor activationComprehensive proteome mapTumor suppressor kinase 1Transcriptional repressionKinase hyperactivationProteome mapTranscriptome analysisGlobal proteomeMFAP2Pathway kinasesProtein succinylationMechanical cuesMetabolic homeostasisKinase 1Potential therapeutic strategySpatial transcriptomicsSpatial transcriptomic analysisHMGCS2LATS1Protein 2Synthase 2Data-independent acquisitionDivergent proteome tolerance against gain and loss of chromosome arms
Di Y, Li W, Castellano J, Jin W, Modi J, Salovska B, Khosroabadi D, Hu W, Taylor A, Liu Y. Divergent proteome tolerance against gain and loss of chromosome arms. Molecular Cell 2025, 85: 4268-4278.e6. PMID: 41270725, DOI: 10.1016/j.molcel.2025.10.023.Peer-Reviewed Original ResearchConceptsChromosome arm gainsProtein complex subunitsStable protein complexesChromosome 3p lossQuantitative mass spectrometryChromosome armsProteostasis mechanismsComplex stoichiometryComplex subunitsProtein complexesEuploid chromosomeComplexation showMass spectrometryProtein degradationThermal stabilityIsotope labelingProtein synthesisProteinChromosomeAneuploidyCell modelHuman lung cell modelLung cell modelProteostasisThe mitotic ATR-Chk1 pathway promotes CDK1 activity for faithful chromosome segregation
Joo Y, Parrado C, Li W, Yang R, Black E, Bleichert F, Liu Y, Kabeche L. The mitotic ATR-Chk1 pathway promotes CDK1 activity for faithful chromosome segregation. Cell Reports 2025, 44: 116019. PMID: 40705605, PMCID: PMC12451630, DOI: 10.1016/j.celrep.2025.116019.Peer-Reviewed Original ResearchConceptsDNA damage responseCdk1 activityATR-Chk1 pathwayChromosome segregationATR-Chk1Aurora B activityResidual activityCheckpoint kinase 1Mitotic progressionCDK1 inhibitionDamage responseRad3-relatedCDK1Lagging chromosomesATR-Chk1 activationHuman cellsChromosomeKinase 1Ataxia telangiectasiaMitosisChk1DNA damageDNAB activityPartial lossA robust multiplex-DIA workflow profiles protein turnover regulations associated with cisplatin resistance and aneuploidy
Salovska B, Li W, Bernhardt O, Germain P, Wang Q, Gandhi T, Reiter L, Liu Y. A robust multiplex-DIA workflow profiles protein turnover regulations associated with cisplatin resistance and aneuploidy. Nature Communications 2025, 16: 5034. PMID: 40447611, PMCID: PMC12125295, DOI: 10.1038/s41467-025-60319-x.Peer-Reviewed Original ResearchConceptsMS platformsMass spectrometryDrug discoveryCisplatin resistanceDegradation kineticsDegradation profileAssociated with cisplatin resistanceProtein turnoverLabeled channelsProtein complex subunitsRespiratory complex IMitochondrial metabolic adaptationRobust workflowProtein degradation profilesCancer cell modelsMeasure protein turnoverProtein turnover regulationProteome dynamicsSpectrometryHigh-throughputComplex ICellular processesComplex subunitsSILAC labelingAneuploid genomesCrystal structure of Isthmin-1 and reassessment of its functional role in pre-adipocyte signaling
Li T, Stayrook S, Li W, Wang Y, Li H, Zhang J, Liu Y, Klein D. Crystal structure of Isthmin-1 and reassessment of its functional role in pre-adipocyte signaling. Nature Communications 2025, 16: 3580. PMID: 40234450, PMCID: PMC12000326, DOI: 10.1038/s41467-025-58828-w.Peer-Reviewed Original ResearchConceptsThrombospondin type I repeatsIsthmin-1Pre-adipocytesType I repeatsBacterial streptavidinSurface helicesI repeatsMolecular detailsDiverse functionsFunctional studiesAkt phosphorylationFunctional roleStructural plasticityInsulin-like propertiesCrystal structureAMOPGrowth factorDomainPhosphorylationApoptosisLiver steatosisProteinHelixAktStreptavidinAn in vivo screen identifies NAT10 as a master regulator of brain metastasis
Chen J, Xu P, Cai W, Chen H, Wingrove E, Shi X, Li W, Biancon G, Zhang M, Balabaki A, Krop E, Asare E, Zhang Y, Yin M, Tebaldi T, Meier J, Westbrook T, Halene S, Liu Y, Shen H, Nguyen D, Yan Q. An in vivo screen identifies NAT10 as a master regulator of brain metastasis. Science Advances 2025, 11: eads6021. PMID: 40138393, PMCID: PMC11939035, DOI: 10.1126/sciadv.ads6021.Peer-Reviewed Original ResearchConceptsPhosphoserine aminotransferase 1Metastasis in vivoIn vivo screeningRNA helicase domainRegulator of brain metastasisMetastatic breast cancer cellsBrain metastasis in vivoBrain metastasesRNA helicaseCell growth in vitroBreast cancer cellsCancer cell proliferationSerine biosynthesisEpigenetic regulationGrowth in vitroNAT10Migration in vitroCancer cellsTumor growthCell proliferationPrimary tumor growthDrivers of brain metastasesRNACancer metastasisCancer-related deathsTurnover atlas of proteome and phosphoproteome across mouse tissues and brain regions
Li W, Dasgupta A, Yang K, Wang S, Hemandhar-Kumar N, Chepyala S, Yarbro J, Hu Z, Salovska B, Fornasiero E, Peng J, Liu Y. Turnover atlas of proteome and phosphoproteome across mouse tissues and brain regions. Cell 2025, 188: 2267-2287.e21. PMID: 40118046, PMCID: PMC12033170, DOI: 10.1016/j.cell.2025.02.021.Peer-Reviewed Original ResearchConceptsMouse tissuesNeurodegeneration-related proteinsPost-translational modificationsImpact of phosphorylationStable isotope labelingLong-lived proteinsPeroxisomal proteinsProtein lifetimeProteomic propertiesProtein phosphorylationProtein stabilityInteractive web-based portalProtein abundanceProtein turnoverPhosphorylationMammalian tissuesComprehensive resourceProteinIsotope labelingProteomicsA-synucleinAbundanceTurnoverTurnover changesPhosphosites
2024
Chk2 sustains PLK1 activity in mitosis to ensure proper chromosome segregation
Black E, Ramírez Parrado C, Trier I, Li W, Joo Y, Pichurin J, Liu Y, Kabeche L. Chk2 sustains PLK1 activity in mitosis to ensure proper chromosome segregation. Nature Communications 2024, 15: 10782. PMID: 39737931, PMCID: PMC11685634, DOI: 10.1038/s41467-024-54922-7.Peer-Reviewed Original ResearchConceptsPolo-like kinase 1Plk1 activityChromosome segregationMitotic polo-like kinase 1Mitotic chromosome segregationProtecting genome stabilitySensitivity to PLK1 inhibitorsMitotic cell divisionCheckpoint kinase 2Polo-like kinase 1 activityDNA damage repairGenome stabilityChromosome missegregationCytokinetic defectsCell divisionGenomic instabilityT-loopCell cycleKinase activityChromosome misalignmentMitotic errorsChk2Kinase 2Damage repairChromosomeGABAA receptor π forms channels that stimulate ERK through a G-protein-dependent pathway
Wang Y, Zhang Y, Li W, Salovska B, Zhang J, Li T, Li H, Liu Y, Kaczmarek L, Pusztai L, Klein D. GABAA receptor π forms channels that stimulate ERK through a G-protein-dependent pathway. Molecular Cell 2024, 85: 166-176.e5. PMID: 39642883, PMCID: PMC11698630, DOI: 10.1016/j.molcel.2024.11.016.Peer-Reviewed Original ResearchExtracellular regulated kinaseStimulated extracellular regulated kinaseExtracellular-regulated kinase signalingG-protein-dependent pathwayG protein-coupled pathwayUncharacterized pathwayGrowth signalsSignaling functionsCryoelectron microscopyCryo-EMSignaling mechanismsGABRPFunctional assaysNative nanodiscsPathwayStimulate growthPhysiological concentrationsAbsence of GABATargeted inhibitionType A receptorConcentrations of GABAMetabotropic receptorsIonotropic activitySignalGABA bindingA proteome-wide quantitative platform for nanoscale spatially resolved extraction of membrane proteins into native nanodiscs
Brown C, Ghosh S, McAllister R, Kumar M, Walker G, Sun E, Aman T, Panda A, Kumar S, Li W, Coleman J, Liu Y, Rothman J, Bhattacharyya M, Gupta K. A proteome-wide quantitative platform for nanoscale spatially resolved extraction of membrane proteins into native nanodiscs. Nature Methods 2024, 22: 412-421. PMID: 39609567, PMCID: PMC11810782, DOI: 10.1038/s41592-024-02517-x.Peer-Reviewed Original ResearchTarget membrane proteinsMembrane proteinsMembrane contextSynaptic vesicle membrane proteinVesicle membrane proteinsMammalian membrane proteinsMembrane-active polymersExtraction of membrane proteinsNative nanodiscsOrganellar membranesNative membrane environmentMultiprotein complexesMolecular contextCellular membranesMembrane environmentQuantitative platformBioanalytical approachesExtraction efficiencyOpen-access databasesProteinMembraneExtraction conditionsNanodiscsTarget MP
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