2023
Autologous 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 ResearchMeSH KeywordsAnimalsDisease Models, AnimalHumansMedical OncologyMiceNeoplasmsTumor MicroenvironmentVascular Endothelial Growth Factor AConceptsHuman 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 predictions
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 fibrogenesis
2019
Regulated 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 administrationHepatic metabolic adaptation in a murine model of glutathione deficiency
Chen Y, Golla S, Garcia-Milian R, Thompson DC, Gonzalez FJ, Vasiliou V. Hepatic metabolic adaptation in a murine model of glutathione deficiency. Chemico-Biological Interactions 2019, 303: 1-6. PMID: 30794799, PMCID: PMC6743730, DOI: 10.1016/j.cbi.2019.02.015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDisease Models, AnimalFatty LiverGlutamate-Cysteine LigaseGlutathioneHomeostasisLiverMetabolomicsMiceMice, KnockoutOxidation-ReductionConceptsCellular non-protein thiolsMetabolic adaptationGlutamate-cysteine ligase modifier subunitNon-protein thiolsHepatic metabolic adaptationCellular redoxGlobal profilingGSH homeostasisModifier subunitLiver developmentBiochemical mechanismsMetabolic homeostasisAmino acidsGclm null miceDefense mechanismsEnvironmental insultsOxidative damageFatty liver developmentNull miceSpectrum of changesNucleic acidsMetabolic signaturesPivotal roleHomeostasisGlutathione deficiency