2025
Proliferative arrest induces neuronal differentiation and innate immune responses in normal and Creutzfeldt-Jakob Disease agent (CJ) infected rat septal neurons
Pagano N, Perez G, Garcia-Milian R, Manuelidis L. Proliferative arrest induces neuronal differentiation and innate immune responses in normal and Creutzfeldt-Jakob Disease agent (CJ) infected rat septal neurons. PLOS ONE 2025, 20: e0323825. PMID: 40434970, PMCID: PMC12118874, DOI: 10.1371/journal.pone.0323825.Peer-Reviewed Original ResearchConceptsSeptal neuronsInnate immune responseDifferential transcriptionCreutzfeldt-Jakob disease agentCJ infectionImmune responseBind misfolded proteinsInnate immune genesIntestinal myeloid cellsRat septal neuronsArrests normal cellsDisease agentsInnate immune transcriptsCreutzfeldt-JakobModel of latent infectionAnti-viral responseCDNA libraryUnique transcriptsPeripheral human bloodLate-onset diseaseUninfected neuronsUpregulated interferonImmune genesMyeloid cellsTranscriptionTranscriptomic landscape of cumulus cells from patients <38 years old with a history of poor ovarian response (POR) treated with platelet-rich plasma (PRP)
Roberts L, Herlihy N, Reig A, Titus S, Garcia-Milian R, Knight J, Yildirim R, Margolis C, Cakiroglu Y, Tiras B, Whitehead C, Werner M, Seli E. Transcriptomic landscape of cumulus cells from patients <38 years old with a history of poor ovarian response (POR) treated with platelet-rich plasma (PRP). Aging 2025, 17: 431-447. PMID: 39976580, PMCID: PMC11892918, DOI: 10.18632/aging.206202.Peer-Reviewed Original ResearchConceptsPlatelet-rich plasmaTreated with platelet-rich plasmaCumulus cellsPoor ovarian responseLive birthsGene expressionIntraovarian injection of autologous platelet-rich plasmaPatients treated with platelet-rich plasmaInjection of autologous platelet-rich plasmaHistory of poor ovarian responseAutologous platelet-rich plasmaPlatelet-rich plasma treatmentDiminished ovarian reserveCell-to-cell signalingRNA sequencing librariesCause of infertilityDifferential expression analysisFalse discovery rate thresholdIntraovarian injectionOvarian reserveFailed implantsSequencing librariesOvarian responseTranscriptomic landscapeRNA sequencing
2024
The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity
Marin-Lopez A, Huck J, Esterly A, Azcutia V, Rosen C, Garcia-Milian R, Sefik E, Vidal-Pedrola G, Raduwan H, Chen T, Arora G, Halene S, Shaw A, Palm N, Flavell R, Parkos C, Thangamani S, Ring A, Fikrig E. The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity. Science Immunology 2024, 9: eadk9872-eadk9872. PMID: 39121194, PMCID: PMC11924945, DOI: 10.1126/sciimmunol.adk9872.Peer-Reviewed Original ResearchConceptsSuppress antiviral responsesArthropod proteinsPathogen replicationAntiviral responseProtein AVertebrate hostsMosquito salivary proteinsUp-regulatedBlood feedingHuman macrophagesPleomorphic effectsSkin infectionsZika virus disseminationInhibit proinflammatory responsesSalivary proteinsProteinNatural ligandWhite blood cellsHuman skin explantsProinflammatory responseMosquito salivaVirus disseminationHuman CD47Salivary factorsArbovirus infection
2023
Digital spatial profiling of melanoma shows CD95 expression in immune cells is associated with resistance to immunotherapy
Martinez-Morilla S, Moutafi M, Fernandez A, Jessel S, Divakar P, Wong P, Garcia-Milian R, Schalper K, Kluger H, Rimm D. Digital spatial profiling of melanoma shows CD95 expression in immune cells is associated with resistance to immunotherapy. OncoImmunology 2023, 12: 2260618. PMID: 37781235, PMCID: PMC10540659, DOI: 10.1080/2162402x.2023.2260618.Peer-Reviewed Original ResearchConceptsDigital spatial profilingImmune checkpoint inhibitor therapyShorter progression-free survivalQuantitative immunofluorescenceCheckpoint inhibitor therapyProgression-free survivalMetastatic melanoma patientsPre-treatment specimensIndependent validation cohortMetastatic melanoma casesAdjuvant settingNanoString GeoMxMultivariable adjustmentAdverse eventsImmunotherapy cohortInhibitor therapyPD-L1Immune markersMelanoma patientsUnivariable analysisValidation cohortImmune cellsMelanoma casesMultiplex immunofluorescenceCD95 expressionAutologous humanized PDX modeling for immuno-oncology recapitulates features of the human tumor microenvironment
Chiorazzi M, Martinek J, Krasnick B, Zheng Y, Robbins K, Qu R, Kaufmann G, Skidmore Z, Juric M, Henze L, Brösecke F, Adonyi A, Zhao J, Shan L, Sefik E, Mudd J, Bi Y, Goedegebuure S, Griffith M, Griffith O, Oyedeji A, Fertuzinhos S, Garcia-Milian R, Boffa D, Detterbeck F, Dhanasopon A, Blasberg J, Judson B, Gettinger S, Politi K, Kluger Y, Palucka K, Fields R, Flavell R. Autologous humanized PDX modeling for immuno-oncology recapitulates features of the human tumor microenvironment. Journal For ImmunoTherapy Of Cancer 2023, 11: e006921. PMID: 37487666, PMCID: PMC10373695, DOI: 10.1136/jitc-2023-006921.Peer-Reviewed Original ResearchConceptsHuman tumor microenvironmentTumor microenvironmentTumor-immune interactionsSolid tumorsAdaptive immune activationAdaptive immune populationsIndividual tumor microenvironmentsPatient's hematopoietic systemPatient-derived xenograft tissuesVascular endothelial growth factorBone marrow hematopoietic stemBone marrow aspiratePreclinical drug testingEndothelial growth factorHematopoietic systemAutologous tumorPDX modelingPDX miceImmune activationImmune populationsMarrow aspiratesAutologous systemIndividual patientsLittermate controlsPreclinical predictionsPeripheral signature of altered synaptic integrity in young onset cannabis use disorder: A proteomic study of circulating extracellular vesicles
Ganesh S, Lam T, Garcia-Milian R, D'Souza D, Nairn A, Elgert K, Eitan E, Ranganathan M. Peripheral signature of altered synaptic integrity in young onset cannabis use disorder: A proteomic study of circulating extracellular vesicles. The World Journal Of Biological Psychiatry 2023, 24: 603-613. PMID: 36994633, PMCID: PMC10471733, DOI: 10.1080/15622975.2023.2197039.Peer-Reviewed Original ResearchConceptsNeuron-derived extracellular vesiclesLabel-free quantification mass spectrometryProteomic studiesCannabis use disorderExtracellular vesiclesMass spectrometry proteomic analysisDifferential proteomic profilesAdapter proteinProteomic analysisPost-synaptic densityPeripheral signatureMolecular basisProteomic profilesProteinMarkers of neuropathologyBrain tissue samplesSynaptic pathologyVesiclesSynaptic integrityImmunoaffinity methodUse disordersFunctional integrityImportant insightsNeuropathologyPilot studyThe age of bone marrow dictates the clonality of smooth muscle-derived cells in atherosclerotic plaques
Kabir I, Zhang X, Dave J, Chakraborty R, Qu R, Chandran R, Ntokou A, Gallardo-Vara E, Aryal B, Rotllan N, Garcia-Milian R, Hwa J, Kluger Y, Martin K, Fernández-Hernando C, Greif D. The age of bone marrow dictates the clonality of smooth muscle-derived cells in atherosclerotic plaques. Nature Aging 2023, 3: 64-81. PMID: 36743663, PMCID: PMC9894379, DOI: 10.1038/s43587-022-00342-5.Peer-Reviewed Original ResearchConceptsAtherosclerotic plaquesBone marrowSmooth muscle-derived cellsSMC progenitorsAtherosclerotic plaque cellsSmooth muscle cell progenitorsPredominant risk factorCause of deathNovel therapeutic strategiesTNF receptor 1Muscle-derived cellsAged bone marrowAged BMEffect of agePlaque burdenAged miceRisk factorsTumor necrosisTherapeutic strategiesPlaque cellsMyeloid cellsReceptor 1Integrin β3Cell progenitorsAtherosclerosis
2022
Proteomic profiling reveals an association between ALDH and oxidative phosphorylation and DNA damage repair pathways in human colon adenocarcinoma stem cells
Wang Y, Chen Y, Garcia-Milian R, Golla JP, Charkoftaki G, Lam TT, Thompson DC, Vasiliou V. Proteomic profiling reveals an association between ALDH and oxidative phosphorylation and DNA damage repair pathways in human colon adenocarcinoma stem cells. Chemico-Biological Interactions 2022, 368: 110175. PMID: 36162455, PMCID: PMC9891852, DOI: 10.1016/j.cbi.2022.110175.Peer-Reviewed Original ResearchConceptsCancer stem cellsProteomic profilingOxidative phosphorylationLabel-free quantitative proteomic analysisDNA damage repair pathwaysQuantitative proteomic analysisAldehyde dehydrogenase familyColon cancer stem cellsCOLO320DM cellsStem cellsNucleotide excision repairDamage repair pathwaysIngenuity Pathway AnalysisCell populationsProteomic analysisProteomic datasetsDehydrogenase familyMetabolic switchProteomic studiesRepair pathwaysCellular pathwaysALDH enzymatic activityCellular survivalExcision repairALDH activityHIV viral transcription and immune perturbations in the CNS of people with HIV despite ART
Farhadian SF, Lindenbaum O, Zhao J, Corley MJ, Im Y, Walsh H, Vecchio A, Garcia-Milian R, Chiarella J, Chintanaphol M, Calvi R, Wang G, Ndhlovu LC, Yoon J, Trotta D, Ma S, Kluger Y, Spudich S. HIV viral transcription and immune perturbations in the CNS of people with HIV despite ART. JCI Insight 2022, 7: e160267. PMID: 35801589, PMCID: PMC9310520, DOI: 10.1172/jci.insight.160267.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidHIV infectionHIV-1-infected cellsCNS viral persistenceCentral memory CD4T-cell abnormalitiesHIV-1 RNAMicroglia-like cellsT cell activationSystemic viral suppressionAbnormal CD8HIV neuropathogenesisViral suppressionMemory CD4CNS reservoirsImmune perturbationsExperience elevated ratesNeuroimmune effectsPeripheral bloodNeurological impairmentViral persistenceT cellsCell abnormalitiesUninfected controlsCell activation
2021
Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis
Chandran RR, Xie Y, Gallardo-Vara E, Adams T, Garcia-Milian R, Kabir I, Sheikh AQ, Kaminski N, Martin KA, Herzog EL, Greif DM. Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis. Nature Communications 2021, 12: 7179. PMID: 34893592, PMCID: PMC8664937, DOI: 10.1038/s41467-021-27499-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationDisease Models, AnimalDown-RegulationExtracellular MatrixFemaleFibroblastsFibrosisHumansKruppel-Like Factor 4LungLung InjuryMaleMesenchymal Stem CellsMiceMice, Inbred C57BLMyofibroblastsReceptor, Platelet-Derived Growth Factor betaRespiratory Tract DiseasesSignal TransductionTransforming Growth Factor betaConceptsMesenchymal cell typesPlatelet-derived growth factor receptorSmooth muscle actinLung fibrosisKruppel-like factor 4Forkhead box M1Growth factor receptorCell transitionCell typesExtracellular matrixDistinct rolesKLF4Box M1C chemokine ligandMesenchymal cell subtypesFactor receptorPro-fibrotic effectsFactor 4PDGFRMesenchymeCellsMacrophage accumulationKLF4 levelsChemokine ligandLung fibrogenesisCellular and Molecular Diversity in Scleroderma
Hinchcliff M, Garcia-Milian R, Di Donato S, Dill K, Bundschuh E, Galdo FD. Cellular and Molecular Diversity in Scleroderma. Seminars In Immunology 2021, 58: 101648. PMID: 35940960, DOI: 10.1016/j.smim.2022.101648.Peer-Reviewed Original ResearchConceptsSystemic sclerosisMedicine approachVariable clinical outcomesPrecision medicine approachPersonalized medicine approachClinical outcomesSame diagnosisDisease heterogeneityDisease riskCare promisesPatient heterogeneityRoutine integrationMolecular heterogeneityMolecular underpinningsSclerosisPatientsSclerodermaHistopathologyMolecular basisArmamentariumFindingsDiagnosisDesmosterol suppresses macrophage inflammasome activation and protects against vascular inflammation and atherosclerosis
Zhang X, McDonald JG, Aryal B, Canfrán-Duque A, Goldberg EL, Araldi E, Ding W, Fan Y, Thompson BM, Singh AK, Li Q, Tellides G, Ordovás-Montanes J, García Milian R, Dixit VD, Ikonen E, Suárez Y, Fernández-Hernando C. Desmosterol suppresses macrophage inflammasome activation and protects against vascular inflammation and atherosclerosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2107682118. PMID: 34782454, PMCID: PMC8617522, DOI: 10.1073/pnas.2107682118.Peer-Reviewed Original ResearchConceptsCholesterol biosynthetic intermediatesBiosynthetic intermediatesDependent inflammasome activationSingle-cell transcriptomicsMitochondrial reactive oxygen species productionFoam cell formationMacrophage foam cellsReactive oxygen species productionHuman coronary artery lesionsConversion of desmosterolTranscriptomic analysisMacrophage cholesterol metabolismPhysiological contextOxygen species productionLiver X receptor ligandsApoptosis-associated speck-like proteinRetinoid X receptor activationX receptor ligandsInflammasome activationAtherosclerotic plaquesSpeck-like proteinCholesterol homeostasisMacrophage inflammasome activationKey moleculesCell formationImpaired GSH biosynthesis disrupts eye development, lens morphogenesis and PAX6 function
Thompson B, Chen Y, Davidson EA, Garcia-Milian R, Golla JP, Apostolopoulos N, Orlicky DJ, Schey K, Thompson DC, Vasiliou V. Impaired GSH biosynthesis disrupts eye development, lens morphogenesis and PAX6 function. The Ocular Surface 2021, 22: 190-203. PMID: 34425299, PMCID: PMC8560581, DOI: 10.1016/j.jtos.2021.08.010.Peer-Reviewed Original ResearchConceptsHEK293T cellsEye developmentGSH biosynthesisTransactivation activityPax6 functionReactive oxygen speciesSubsequent gene ontologyCell identity genesButhionine sulfoximineEpithelial cell identityRNA-seq analysisIngenuity Pathway AnalysisKey upstream regulatorIdentity genesCell identityGene OntologyRNA-seqImmune response genesBioinformatics analysisResponse genesGlutathione biosynthesisLens morphogenesisMolecular consequencesUpstream regulatorMicrophthalmia phenotypeCumulus cells of euploid versus whole chromosome 21 aneuploid embryos reveal differentially expressed genes
Tiegs AW, Titus S, Mehta S, Garcia-Milian R, Seli E, Scott RT. Cumulus cells of euploid versus whole chromosome 21 aneuploid embryos reveal differentially expressed genes. Reproductive BioMedicine Online 2021, 43: 614-626. PMID: 34417138, DOI: 10.1016/j.rbmo.2021.06.015.Peer-Reviewed Original ResearchConceptsSerum response factorCumulus cellsDifferential gene expressionRNA sequencing analysisGene expression analysisIngenuity Pathway AnalysisCellular communication network factor 1Embryo developmental competenceExpression analysisPreimplantation embryo qualityGene expressionPathway analysisSegment polarity protein 2Sequencing analysisGenesProtein 2Response factorTrisomy 21Factor 1Developmental competenceAneuploid embryosReal-time polymerase chain reaction assaysDevelopment of biomarkersEmbryosCellsIndividual-oocyte transcriptomic analysis shows that genotoxic chemotherapy depletes human primordial follicle reserve in vivo by triggering proapoptotic pathways without growth activation
Titus S, Szymanska K, Musul B, Turan V, Taylan E, Garcia- Milian R, Mehta S, Oktay K. Individual-oocyte transcriptomic analysis shows that genotoxic chemotherapy depletes human primordial follicle reserve in vivo by triggering proapoptotic pathways without growth activation. Scientific Reports 2021, 11: 407. PMID: 33431979, PMCID: PMC7801500, DOI: 10.1038/s41598-020-79643-x.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisCyclophosphamideDNA DamageFemaleGene Expression ProfilingHeterograftsHumansMiceMice, Inbred NODMice, SCIDOocytesOogenesisOvarian FollicleOvarian ReserveOvarySignal TransductionSingle-Cell AnalysisTranscriptomeYoung AdultConceptsPrimordial follicle oocytesFollicle lossGrowth activationHuman ovarian xenograft modelPI3K/PTEN/AktFollicle oocytesDNA damagePI3K/PTEN/Akt pathwayOvarian reserve depletionPrimordial follicle reservePTEN/AKT pathwayIngenuity Pathway AnalysisOvarian xenograft modelPTEN/AKTSevere DNA damageExpression of AktGonadotoxic chemotherapyAnti-apoptotic Bcl2Early menopauseFollicle reserveTranscriptomic analysisCyclophosphamide injectionHuman ovaryPhosphorylation statusRNA sequencing
2020
Acetaminophen Attenuates invasion and alters the expression of extracellular matrix enzymes and vascular factors in human first trimester trophoblast cells
Burman A, Garcia-Milian R, Wood M, DeWitt NA, Vasiliou V, Guller S, Abrahams VM, Whirledge S. Acetaminophen Attenuates invasion and alters the expression of extracellular matrix enzymes and vascular factors in human first trimester trophoblast cells. Placenta 2020, 104: 146-160. PMID: 33348283, DOI: 10.1016/j.placenta.2020.12.002.Peer-Reviewed Original ResearchConceptsFirst trimester trophoblast cellsHuman first trimester trophoblast cellsPrenatal acetaminophen useTrophoblast cellsAcetaminophen useTrophoblast functionsAcetaminophen exposureFetal developmentHTR-8/SVneo cellsPrenatal acetaminophen exposureAnti-inflammatory drug aspirinRecent epidemiological studiesPlacental cell typesMatrix metalloproteinases 2Expression of angiogenesisExtracellular matrix enzymesPrenatal acetaminophenCommon medicationsVascular factorsMaternal healthPlacental functionEpidemiological associationLong-term effectsCyclooxygenase-1Epidemiological studiesGene X environment: the cellular environment governs the transcriptional response to environmental chemicals
Burman A, Garcia-Milian R, Whirledge S. Gene X environment: the cellular environment governs the transcriptional response to environmental chemicals. Human Genomics 2020, 14: 19. PMID: 32448403, PMCID: PMC7247264, DOI: 10.1186/s40246-020-00269-1.Peer-Reviewed Original ResearchConceptsTranscriptional responseCellular environmentCellular contextGenetic sexUnique gene networksGene regulatory networksEnvironment interactionEnvironmental chemicalsGene expression studiesUnique transcriptional profileGene expression array dataExpression array dataPhenotype of cellsGene networksRegulatory networksTranscriptional profilesBiological functionsCellular organizationExpression studiesFemale cellsCellular responsesPhysiological cuesHuman gene expression studiesMolecular pathwaysGenetic resultsKTN1 variants and risk for attention deficit hyperactivity disorder
Luo X, Guo X, Tan Y, Zhang Y, Garcia‐Milian R, Wang Z, Shi J, Yu T, Ji J, Wang X, Xu J, Zhang H, Zuo L, Lu L, Wang K, Li C. KTN1 variants and risk for attention deficit hyperactivity disorder. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2020, 183: 234-244. PMID: 32190980, PMCID: PMC7210069, DOI: 10.1002/ajmg.b.32782.Peer-Reviewed Original Research
2019
Determining the endocrine disruption potential of industrial chemicals using an integrative approach: Public databases, in vitro exposure, and modeling receptor interactions
Alofe O, Kisanga E, Inayat-Hussain SH, Fukumura M, Garcia-Milian R, Perera L, Vasiliou V, Whirledge S. Determining the endocrine disruption potential of industrial chemicals using an integrative approach: Public databases, in vitro exposure, and modeling receptor interactions. Environment International 2019, 131: 104969. PMID: 31310931, PMCID: PMC6728168, DOI: 10.1016/j.envint.2019.104969.Peer-Reviewed Original ResearchConceptsEstrogen receptorEstradiol-mediated inductionLow-dose combinationIshikawa cell lineLow-dose effectsDirect stimulatoryPotential of chemicalsRate of proliferationOccupational exposureIshikawa cellsAnimal modelsHuman studiesReproductive toxicityCarcinogenic effectsInhibitory effectToxicology testingEndocrineCell proliferationEndocrine disruption potentialDose effectReceptor interactionIndustrial chemicalsCell linesPublic healthAdditive effectRegulated necrosis and failed repair in cisplatin-induced chronic kidney disease
Landau SI, Guo X, Velazquez H, Torres R, Olson E, Garcia-Milian R, Moeckel GW, Desir GV, Safirstein R. Regulated necrosis and failed repair in cisplatin-induced chronic kidney disease. Kidney International 2019, 95: 797-814. PMID: 30904067, PMCID: PMC6543531, DOI: 10.1016/j.kint.2018.11.042.Peer-Reviewed Original ResearchConceptsChronic kidney diseaseKidney diseaseKidney injuryCisplatin-induced chronic kidney diseaseCisplatin-induced acute kidney injuryToll-like receptor 2Regulated necrosis pathwaysReversible kidney injuryAcute kidney injuryChronic kidney injuryProximal tubular damageKidney injury markersDoses of cisplatinEvidence of fibrosisMechanisms of progressionEffective chemotherapeutic agentWestern blot analysisFirst doseInjury markersIntraperitoneal cisplatinSignificant nephrotoxicityTubular damageKidney functionSecond doseCisplatin administration
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