2023
Multiscale genetic architecture of donor-recipient differences reveals intronic LIMS1 mismatches associated with kidney transplant survival
Sun Z, Zhang Z, Banu K, Gibson I, Colvin R, Yi Z, Zhang W, De Kumar B, Reghuvaran A, Pell J, Manes T, Djamali A, Gallon L, O'Connell P, He J, Pober J, Heeger P, Menon M. Multiscale genetic architecture of donor-recipient differences reveals intronic LIMS1 mismatches associated with kidney transplant survival. Journal Of Clinical Investigation 2023, 133: e170420. PMID: 37676733, PMCID: PMC10617779, DOI: 10.1172/jci170420.Peer-Reviewed Original ResearchConceptsDeath-censored graft lossHuman leukocyte antigenExpression quantitative trait lociT cellsTGF-β1TGF-β1/Smad pathwayDonor-recipient differencesKidney allograft lossChronic allograft rejectionKidney transplant survivalDonor-recipient mismatchActive TGF-β1Allograft lossGraft lossAllograft rejectionTransplant cohortPeripheral bloodLeukocyte antigenClinical trialsImmune cellsHaplotype mismatchGenome-wide scaleTransplant survivalQuantitative trait lociSingle nucleotide polymorphism dataHCK induces macrophage activation to promote renal inflammation and fibrosis via suppression of autophagy
Chen M, Menon M, Wang W, Fu J, Yi Z, Sun Z, Liu J, Li Z, Mou L, Banu K, Lee S, Dai Y, Anandakrishnan N, Azeloglu E, Lee K, Zhang W, Das B, He J, Wei C. HCK induces macrophage activation to promote renal inflammation and fibrosis via suppression of autophagy. Nature Communications 2023, 14: 4297. PMID: 37463911, PMCID: PMC10354075, DOI: 10.1038/s41467-023-40086-3.Peer-Reviewed Original ResearchConceptsChronic kidney diseasePro-inflammatory polarizationBone marrow-derived macrophagesRenal inflammationKidney fibrosisMacrophage activationHematopoietic cell kinaseMacrophage pro-inflammatory activityProgressive chronic kidney diseaseIschemia-reperfusion injury modelUnilateral ureteral obstruction kidneysChronic allograft injuryReperfusion injury modelPro-inflammatory activityPro-inflammatory macrophagesHck inhibitorsMarrow-derived macrophagesSuppression of autophagyAllograft injuryUUO miceRenal fibrosisKidney diseaseDiseased kidneysMacrophage numbersInjury model
2022
Donor–Recipient Non-HLA Variants, Mismatches and Renal Allograft Outcomes: Evolving Paradigms
Jethwani P, Rao A, Bow L, Menon MC. Donor–Recipient Non-HLA Variants, Mismatches and Renal Allograft Outcomes: Evolving Paradigms. Frontiers In Immunology 2022, 13: 822353. PMID: 35432337, PMCID: PMC9012490, DOI: 10.3389/fimmu.2022.822353.Peer-Reviewed Original ResearchConceptsAllograft outcomesImportant recent dataRenal allograft outcomeAcute allograft rejectionKidney allograft outcomesDonor-recipient mismatchRecipient's immune systemNatural history studiesNon-HLA lociMajority of casesOrgan allocation processPolymorphic HLA genesAcute rejectionAllograft longevityAllograft lossMaintenance immunosuppressionTransplant outcomesAllograft rejectionImmune mechanismsPatient deathRecipient pairsDonor organsHLA variantsImmune systemOvert evidence
2021
Deep learning identified pathological abnormalities predictive of graft loss in kidney transplant biopsies
Yi Z, Salem F, Menon MC, Keung K, Xi C, Hultin S, Haroon Al Rasheed MR, Li L, Su F, Sun Z, Wei C, Huang W, Fredericks S, Lin Q, Banu K, Wong G, Rogers NM, Farouk S, Cravedi P, Shingde M, Smith RN, Rosales IA, O'Connell PJ, Colvin RB, Murphy B, Zhang W. Deep learning identified pathological abnormalities predictive of graft loss in kidney transplant biopsies. Kidney International 2021, 101: 288-298. PMID: 34757124, PMCID: PMC10285669, DOI: 10.1016/j.kint.2021.09.028.Peer-Reviewed Original ResearchConceptsGraft lossTransplant biopsiesDamage scoreBanff scoresPathological lesionsOne-year graft lossPost-transplant graft lossGlomerular filtration rate declineIntermediate-risk groupKidney allograft failurePost-transplant biopsiesKidney transplant biopsiesMononuclear leukocyte infiltrationTissue compartmentsMononuclear leukocyte infiltrateProtocol biopsiesAllograft failureTransplant recipientsClinical predictorsTubular atrophyGraft damageRisk stratificationInterstitial fibrosisLeukocyte infiltrationLeukocyte infiltrate
2020
Genome-wide non-HLA donor-recipient genetic differences influence renal allograft survival via early allograft fibrosis
Zhang Z, Menon MC, Zhang W, Stahl E, Loza BL, Rosales IA, Yi Z, Banu K, Garzon F, Sun Z, Wei C, Huang W, Lin Q, Israni A, Keating BJ, Colvin RB, Hao K, Murphy B. Genome-wide non-HLA donor-recipient genetic differences influence renal allograft survival via early allograft fibrosis. Kidney International 2020, 98: 758-768. PMID: 32454123, PMCID: PMC7483801, DOI: 10.1016/j.kint.2020.04.039.Peer-Reviewed Original ResearchConceptsAllograft survivalIntimal fibrosisDeath-censored allograft survivalLong-term allograft failureAcute rejection episodesDonor-recipient differencesRenal allograft survivalHuman leukocyte antigen (HLA) lociNon-HLA SNPsLong-term survivalAllograft failureHLA mismatchesKidney recipientsRejection episodesSubclinical rejectionAllograft fibrosisMultivariable analysisHistologic damageR differencesOrgan SharingCox modelFibrosisHLA regionSurvivalGenome-wide single-nucleotide polymorphism array data
2018
SHROOM3-FYN Interaction Regulates Nephrin Phosphorylation and Affects Albuminuria in Allografts
Wei C, Banu K, Garzon F, Basgen JM, Philippe N, Yi Z, Liu R, Choudhuri J, Fribourg M, Liu T, Cumpelik A, Wong J, Khan M, Das B, Keung K, Salem F, Campbell KN, Kaufman L, Cravedi P, Zhang W, O'Connell PJ, He JC, Murphy B, Menon MC. SHROOM3-FYN Interaction Regulates Nephrin Phosphorylation and Affects Albuminuria in Allografts. Journal Of The American Society Of Nephrology 2018, 29: 2641-2657. PMID: 30341149, PMCID: PMC6218856, DOI: 10.1681/asn.2018060573.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonAdolescentAdultAgedAlbuminuriaAllograftsAnimalsChildChild, PreschoolEnhancer Elements, GeneticFemaleGene Knockdown TechniquesGlomerular Filtration RateHomozygoteHumansKidneyKidney TransplantationMaleMembrane ProteinsMiceMice, 129 StrainMice, Inbred C57BLMice, KnockoutMicrofilament ProteinsMiddle AgedPhosphorylationPodocytesPolymorphism, Single NucleotideProto-Oncogene Proteins c-fynRenal Insufficiency, ChronicRNA, Small InterferingSignal TransductionSrc Homology DomainsYoung AdultConceptsDiffuse foot process effacementKnockdown miceFoot process effacementReduced albuminuriaAllograft fibrosisRenal functionDonor kidneysLower GFRRenal fibrosisTGF-b signalingHuman allograftsNephroseq databaseBiopsy samplesProcess effacementProtective roleAlbuminuriaAdult glomeruliHuman podocytesKnockdown podocytesCKDHuman dataPodocytesAllograftsActin cytoskeleton pathwayFibrosis
2016
Biopsy transcriptome expression profiling to identify kidney transplants at risk of chronic injury: a multicentre, prospective study
O'Connell PJ, Zhang W, Menon MC, Yi Z, Schröppel B, Gallon L, Luan Y, Rosales IA, Ge Y, Losic B, Xi C, Woytovich C, Keung KL, Wei C, Greene I, Overbey J, Bagiella E, Najafian N, Samaniego M, Djamali A, Alexander SI, Nankivell BJ, Chapman JR, Smith RN, Colvin R, Murphy B. Biopsy transcriptome expression profiling to identify kidney transplants at risk of chronic injury: a multicentre, prospective study. The Lancet 2016, 388: 983-993. PMID: 27452608, PMCID: PMC5014570, DOI: 10.1016/s0140-6736(16)30826-1.Peer-Reviewed Original ResearchConceptsChronic allograft damage indexAllograft lossKidney transplantPathological variablesChronic injuryEarly allograft lossKidney transplant recipientsRenal allograft recipientsFunction 3 monthsBaseline clinical variablesDevelopment of fibrosisAllograft recipientsNormal allograftsRenal allograftsTransplant recipientsAllograft fibrosisMulticentre studyProgressive injuryProspective studyClinical variablesIndependent cohortLower riskFibrosisPredictive valueTransplant
2014
Intronic locus determines SHROOM3 expression and potentiates renal allograft fibrosis
Menon MC, Chuang PY, Li Z, Wei C, Zhang W, Luan Y, Yi Z, Xiong H, Woytovich C, Greene I, Overbey J, Rosales I, Bagiella E, Chen R, Ma M, Li L, Ding W, Djamali A, Saminego M, O’Connell P, Gallon L, Colvin R, Schroppel B, He JC, Murphy B. Intronic locus determines SHROOM3 expression and potentiates renal allograft fibrosis. Journal Of Clinical Investigation 2014, 125: 208-221. PMID: 25437874, PMCID: PMC4382250, DOI: 10.1172/jci76902.Peer-Reviewed Original ResearchMeSH KeywordsAllograftsAnimalsBeta CateninDisease SusceptibilityEnhancer Elements, GeneticFibrosisGene ExpressionGenetic Association StudiesGenetic LociHEK293 CellsHumansIntronsKidneyKidney DiseasesKidney TransplantationMaleMiceMicrofilament ProteinsPolymorphism, Single NucleotideQuantitative Trait LociRiskSmad3 ProteinTranscription Factor 7-Like 2 ProteinTranscriptional ActivationTransforming Growth Factor beta1ConceptsChronic allograft nephropathyChronic kidney diseaseAllograft fibrosisTGF-β1Development of CANRisk allelesKidney transplant recipientsRenal allograft recipientsGlomerular filtration rateRenal allograft fibrosisTGF-β1 administrationUnilateral ureteric obstructionRenal tubular cellsTranscription factor 7Canonical TGF-β1Cell-specific knockdownAllograft injuryAllograft nephropathyAllograft recipientsTransplant recipientsProspective cohortRenal functionInterstitial fibrosisUreteric obstructionKidney disease