Wenxue Li
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2026
PI3K Regulates Wild-type RAS Signaling to Confer Resistance to KRAS Inhibition.
Ge X, Singh J, Li W, Markham C, Ruiz C, Stites E, Bhattacharyya M, Liu Y, Muzumdar M. PI3K Regulates Wild-type RAS Signaling to Confer Resistance to KRAS Inhibition. Cancer Research 2026 PMID: 42095550, DOI: 10.1158/0008-5472.can-25-3625.Peer-Reviewed Original ResearchThis study investigates how PI3K enables pancreatic cancer cells to resist KRAS inhibitors by activating wild-type RAS signaling, suggesting combined PI3K-KRAS targeting as a therapeutic strategy.Early-activated extracellular matrix proteins shape the metabolic and spatial dynamics of the kidney fibrotic microenvironment
Gui Y, Li W, Liu J, Wang Y, Jones C, Bansal R, Mallari S, Shaffer H, Yu Y, Fu H, Tang T, Liu S, Liu Y, Zhou D. Early-activated extracellular matrix proteins shape the metabolic and spatial dynamics of the kidney fibrotic microenvironment. Nature Metabolism 2026, 8: 604-623. PMID: 41776110, DOI: 10.1038/s42255-026-01458-3.Peer-Reviewed Original ResearchConceptsOxidative phosphorylationMatrix proteinsExtracellular matrixMitochondrial oxidative phosphorylationYAP nuclear translocationExtracellular matrix proteinsMitochondrial reprogrammingYAP activityMetabolic reprogrammingYAP inactivationFibroblast-specific deletionNuclear translocationAberrant activationSpatial transcriptomicsECM1Spontaneous fibrosisYAPECM changesFibrotic microenvironmentDeletionCellular crosstalkReprogrammingComplex formationProteinSpatial dynamics
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 PMID: 41563281, 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, PMCID: PMC12991381, DOI: 10.1016/j.molcel.2025.10.023.Peer-Reviewed Original ResearchThis study investigates how cells tolerate chromosome arm aneuploidy, showing distinct mechanisms where protein degradation compensates for gains, while synthesis upregulates proteins in losses to maintain balance.The 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, RamÃrez 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 repairChromosome
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