Leyuan Xu, PhD
Assistant ProfessorCards
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2025
Natural killer cell infiltration elicits gender‐dependent dichotomous clinical outcomes in urothelial carcinoma
Zhang L, Liu Z, Ding Y, Sun J, Wu Y, Su X, Jin K, Zeng H, Liu H, Chang Y, Zhu Y, Wang Z, Xu L, Zhang W, Xu J. Natural killer cell infiltration elicits gender‐dependent dichotomous clinical outcomes in urothelial carcinoma. Cancer 2025, 131: e70196. PMID: 41368948, DOI: 10.1002/cncr.70196.Peer-Reviewed Original ResearchConceptsTumor immune microenvironmentNK cellsUrothelial carcinomaNatural killerAbundant infiltrationMale patientsClinical outcomesAssociation of NK cellsNatural killer cell infiltrationInfiltration of dendritic cellsTertiary lymphoid structure formationDichotomous clinical outcomesNK cell phenotypeEffector T cellsCell infiltration levelsAntitumor microenvironmentImmunotherapy strategiesNK infiltrationImmune microenvironmentDendritic cellsImmune profileT cellsInfiltration levelsRetrospective studyImmune cellsClinicopathological and molecular correlates of clinical benefit from disitamab vedotin (RC48), a HER-2-targeting antibody-drug conjugate, in metastatic urothelial carcinoma: a multi-center, real-world study
Liu Z, Jin K, Xu Z, Zeng H, Su X, Xu J, Ding Y, Liu H, Zhu Y, Xu L, Xu J, Wang Z, Chang Y. Clinicopathological and molecular correlates of clinical benefit from disitamab vedotin (RC48), a HER-2-targeting antibody-drug conjugate, in metastatic urothelial carcinoma: a multi-center, real-world study. BMC Cancer 2025, 25: 1432. PMID: 40999345, PMCID: PMC12465952, DOI: 10.1186/s12885-025-14870-x.Peer-Reviewed Original ResearchConceptsMetastatic urothelial carcinomaProgression-free survivalObjective response rateMetastatic urothelial carcinoma patientsAntibody-drug conjugatesHER-2 expressionHER-2Overall survivalUrothelial carcinomaClinical benefitIncidence of treatment-related adverse eventsTreatment-related adverse eventsMedian follow-up timeMulti-centerPositive response to chemotherapyResponse ratePlatinum-based chemotherapyProlonged clinical benefitResponse to chemotherapyFollow-up timeReal-world studyDisitamab vedotinMedian OSOS ratesMutational burdenARID1A Loss plus CD8+ T-Cell Infiltration Associate with Favorable Clinical Outcomes in Urothelial Carcinoma
Liu Z, Zhang L, Jin K, Zeng H, Su X, Ding Y, Sun J, Wu Y, Liu H, Zhu Y, Xu L, Zhang W, Wang Z, Chang Y, Xu J. ARID1A Loss plus CD8+ T-Cell Infiltration Associate with Favorable Clinical Outcomes in Urothelial Carcinoma. Clinical Cancer Research 2025, 31: 4311-4322. PMID: 40788182, PMCID: PMC12521915, DOI: 10.1158/1078-0432.ccr-25-0816.Peer-Reviewed Original ResearchConceptsCD8+ T cell infiltrationT cell infiltrationCD8+ T cellsUrothelial carcinomaT cellsClinical outcomesAntitumor functionARID1A lossInfiltration of CD8+ T cellsFunction of CD8+ T cellsCD8+ T cell functionPD-1/PD-L1 blockadeClinical relevanceImmune microenvironment profilesImmune-suppressive cellsFavorable clinical outcomesTertiary lymphoid structuresTumor-associated macrophagesT cell functionExpression of checkpointsSwitch/sucrose nonfermentable complexImmune contextureIMvigor210 cohortB7-H4B7-H3
2024
Adamts1 and Cyst Expansion in Polycystic Kidney Disease
Kakade V, Akman Z, Motrapu M, Cassini M, Xu L, Moeckel G, Somlo S, Cantley L. Adamts1 and Cyst Expansion in Polycystic Kidney Disease. Journal Of The American Society Of Nephrology 2024, 36: 559-570. PMID: 39514301, PMCID: PMC11975248, DOI: 10.1681/asn.0000000557.Peer-Reviewed Original ResearchAutosomal dominant polycystic kidney diseasePolycystic kidney diseaseKidney diseaseLoss of Pkd1Cyst growthInterstitial macrophage accumulationDominant polycystic kidney diseaseInterstitial mononuclear cellsReduced cyst growthDetectable phenotypeMembrane remodelingMotif 1Progressive cyst growthIsoforms of versicanSimultaneous deletionPKD2 geneTubular basement membraneDisintegrin and metalloproteinaseRNA sequencingBasement membrane remodelingPKD1Thrombospondin motifs 1Cystic enlargementMacrophage accumulationCystic dilatationVCAM-1 mediates proximal tubule-immune cell cross talk in failed tubule recovery during AKI-to-CKD transition
Melchinger I, Guo K, Li X, Guo J, Cantley L, Xu L. VCAM-1 mediates proximal tubule-immune cell cross talk in failed tubule recovery during AKI-to-CKD transition. American Journal Of Physiology. Renal Physiology 2024, 327: f610-f622. PMID: 39116349, PMCID: PMC11483080, DOI: 10.1152/ajprenal.00076.2024.Peer-Reviewed Original ResearchAcute kidney injuryChronic kidney diseaseVCAM-1 expressionProximal tubule cellsVCAM-1Tubule cellsKidney Precision Medicine ProjectProinflammatory cytokinesAcute kidney injury to chronic kidney diseaseModel of chronic kidney diseaseExpression of vascular cell adhesion protein 1Cell adhesion pathwaysInflammatory response to injuryInjured proximal tubule cellsVascular cell adhesion protein 1Mouse model of chronic kidney diseaseRisk of progressionChronic kidney disease transitionIncreased immune cell adhesionVCAM-1-positive cellsOverexpression of VCAM-1Inhibition of NF-kB signalingActivation of NF-kBImmune cell adhesionSingle-cell transcriptome analysis
2023
Analysis of the human kidney transcriptome and plasma proteome identifies markers of proximal tubule maladaptation to injury
Wen Y, Su E, Xu L, Menez S, Moledina D, Obeid W, Palevsky P, Mansour S, Devarajan P, Cantley L, Cahan P, Parikh C, Project K, Injury T. Analysis of the human kidney transcriptome and plasma proteome identifies markers of proximal tubule maladaptation to injury. Science Translational Medicine 2023, 15: eade7287. PMID: 38091407, PMCID: PMC11405121, DOI: 10.1126/scitranslmed.ade7287.Peer-Reviewed Original ResearchThe ASSESS-AKI Study found urinary epidermal growth factor is associated with reduced risk of major adverse kidney events
Menez S, Wen Y, Xu L, Moledina D, Thiessen-Philbrook H, Hu D, Obeid W, Bhatraju P, Ikizler T, Siew E, Chinchilli V, Garg A, Go A, Liu K, Kaufman J, Kimmel P, Himmelfarb J, Coca S, Cantley L, Parikh C. The ASSESS-AKI Study found urinary epidermal growth factor is associated with reduced risk of major adverse kidney events. Kidney International 2023, 104: 1194-1205. PMID: 37652206, PMCID: PMC10840723, DOI: 10.1016/j.kint.2023.08.007.Peer-Reviewed Original ResearchConceptsMajor adverse kidney eventsUEGF/CrUrinary epidermal growth factorAdverse kidney eventsChronic kidney diseaseEpidermal growth factorKidney eventsKidney failureEGF expressionUrinary EGF/CrAcute Kidney Injury studyGrowth factorIschemia-reperfusion injuryProportional hazards regressionTubular healthKidney atrophyObservational cohortHospitalized participantsTubular functionClinical findingsHazards regressionKidney diseaseClinical variablesProgressive atrophyUrinary EGFLongitudinal biomarkers and kidney disease progression after acute kidney injury
Wen Y, Xu L, Melchinger I, Thiessen-Philbrook H, Moledina D, Coca S, Hsu C, Go A, Liu K, Siew E, Ikizler T, Chinchilli V, Kaufman J, Kimmel P, Himmelfarb J, Cantley L, Parikh C, Consortium T. Longitudinal biomarkers and kidney disease progression after acute kidney injury. JCI Insight 2023, 8: e167731. PMID: 36951957, PMCID: PMC10243801, DOI: 10.1172/jci.insight.167731.Peer-Reviewed Original ResearchConceptsAcute kidney injuryIschemic reperfusion injuryKidney disease progressionKidney injuryTubular healthDisease progressionChronic kidney disease (CKD) incidenceCox proportional hazards regressionMurine acute kidney injuryKidney disease incidenceUrine KIM-1Proportional hazards regressionCKD progressionCKD transitionUrine uromodulinIncident CKDComposite outcomeKidney atrophyProspective cohortReperfusion injuryHazards regressionKIM-1Prognostic valueMCP-1Initial insult
2022
Urine Uromodulin as a Biomarker of Kidney Tubulointerstitial Fibrosis
Melchinger H, Calderon-Gutierrez F, Obeid W, Xu L, Shaw MM, Luciano RL, Kuperman M, Moeckel GW, Kashgarian M, Wilson FP, Parikh CR, Moledina DG. Urine Uromodulin as a Biomarker of Kidney Tubulointerstitial Fibrosis. Clinical Journal Of The American Society Of Nephrology 2022, 17: 1284-1292. PMID: 35948365, PMCID: PMC9625093, DOI: 10.2215/cjn.04360422.Peer-Reviewed Original ResearchConceptsInterstitial fibrosis/tubular atrophyUrine uromodulinTubular atrophyThick ascending limbUrine albuminSerum creatinineKidney biopsyTubulointerstitial fibrosisMultivariable linear regression modelsTime of biopsyKidney's thick ascending limbAcademic medical centerHuman kidney biopsiesKidney tubulointerstitial fibrosisTubular healthMultivariable analysisHistologic featuresHistologic findingsHistologic changesKidney fibrosisIndependent associationFibrotic modelMultivariable modelMedical CenterMurine modelImmune-mediated tubule atrophy promotes acute kidney injury to chronic kidney disease transition
Xu L, Guo J, Moledina DG, Cantley LG. Immune-mediated tubule atrophy promotes acute kidney injury to chronic kidney disease transition. Nature Communications 2022, 13: 4892. PMID: 35986026, PMCID: PMC9391331, DOI: 10.1038/s41467-022-32634-0.Peer-Reviewed Original ResearchConceptsAcute kidney injuryKidney injuryT cellsChronic kidney disease transitionIschemia-reperfusion kidney injuryKidney disease transitionChronic kidney diseaseDepletion of neutrophilsGlomerular filtration rateT cell recruitmentTubular cell lossMacrophage persistenceProinflammatory neutrophilsTubule damageKidney atrophyContralateral kidneyNeutrophil numbersContralateral nephrectomyKidney diseaseTubule atrophyFiltration rateCell recruitmentMore macrophagesDay 14Day 5
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