2021
YAP1 nuclear efflux and transcriptional reprograming follow membrane diminution upon VSV-G-induced cell fusion
Feliciano D, Ott CM, Espinosa-Medina I, Weigel AV, Benedetti L, Milano KM, Tang Z, Lee T, Kliman HJ, Guller SM, Lippincott-Schwartz J. YAP1 nuclear efflux and transcriptional reprograming follow membrane diminution upon VSV-G-induced cell fusion. Nature Communications 2021, 12: 4502. PMID: 34301937, PMCID: PMC8302681, DOI: 10.1038/s41467-021-24708-2.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAMP-Activated Protein KinasesAnimalsBiological TransportCell FusionCell LineCell Line, TumorCell MembraneCell NucleusCells, CulturedGiant CellsHEK293 CellsHumansMembrane GlycoproteinsMiceRNA-SeqSignal TransductionTranscription FactorsTranscription, GeneticViral Envelope ProteinsYAP-Signaling ProteinsConceptsCell cycle arrestCell fusionNew cellular statesPlasma membrane surface areaRNA-seq analysisCell fusion systemTranscriptional programsNutrient stressCellular statesTranscriptional changesNuclear effluxCytoplasmic glucoseExtrinsic cuesUndifferentiated cellsGlucose transporterFused cellsMechanistic insightsMembrane surface areaNew functionsEndocytosisYAP1 inhibitionEnergetic stateSyncytiaCellsVSV
2020
NLRP3 inflammasome function and pyroptotic cell death in human placental Hofbauer cells
Abrahams VM, Tang Z, Mor G, Guller S. NLRP3 inflammasome function and pyroptotic cell death in human placental Hofbauer cells. Journal Of Reproductive Immunology 2020, 142: 103214. PMID: 33152658, PMCID: PMC7770077, DOI: 10.1016/j.jri.2020.103214.Peer-Reviewed Original ResearchConceptsHofbauer cellsCaspase-1 activationIL-1β processingIL-1βInflammasome activationFetal inflammatory response syndromeSubsequent pregnancy complicationsInflammatory response syndromeCell deathNLRP3 inflammasome activationInterleukin-1 betaIL-1β secretionInhibition of P2X7Human term placentaGasdermin D cleavageNLRP3 knockdownPlacental inflammationPyroptotic cell deathFetal inflammationHistologic chorioamnionitisPregnancy complicationsResponse syndromeNLRP3 inflammasomeProtein/gene expressionInflammatory form
2017
Low molecular weight heparin and aspirin exacerbate human endometrial endothelial cell responses to antiphospholipid antibodies
Quao ZC, Tong M, Bryce E, Guller S, Chamley LW, Abrahams VM. Low molecular weight heparin and aspirin exacerbate human endometrial endothelial cell responses to antiphospholipid antibodies. American Journal Of Reproductive Immunology 2017, 79 PMID: 29135051, PMCID: PMC5728699, DOI: 10.1111/aji.12785.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, AntiphospholipidAntiphospholipid SyndromeAspirinBeta 2-Glycoprotein ICells, CulturedChemokinesDisease ProgressionDrug Therapy, CombinationEndometriumEndothelial CellsFemaleHeparin, Low-Molecular-WeightHumansMembrane ProteinsNeovascularization, PhysiologicPregnancyPregnancy ComplicationsTrophoblastsVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1ConceptsLow molecular weight heparinHuman endometrial endothelial cellsMolecular weight heparinUterine endotheliumAntiphospholipid antibodiesWeight heparinInfluence of LMWHLow dose low molecular weight heparinAnti-angiogenic sFlt-1Chemokine MCP-1Endometrial endothelial cellsEffects of aPLSFlt-1 releaseAngiogenic factor secretionObstetric APSPregnancy complicationsControl IgGChemokine profilesEndothelium dysfunctionChemokine secretionPro-angiogenic VEGFCombination therapySFlt-1Impaired placentationMCP-1Viral Infection Sensitizes Human Fetal Membranes to Bacterial Lipopolysaccharide by MERTK Inhibition and Inflammasome Activation.
Cross SN, Potter JA, Aldo P, Kwon JY, Pitruzzello M, Tong M, Guller S, Rothlin CV, Mor G, Abrahams VM. Viral Infection Sensitizes Human Fetal Membranes to Bacterial Lipopolysaccharide by MERTK Inhibition and Inflammasome Activation. The Journal Of Immunology 2017, 199: 2885-2895. PMID: 28916522, PMCID: PMC5659726, DOI: 10.4049/jimmunol.1700870.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedChorioamnionitisC-Mer Tyrosine KinaseExtraembryonic MembranesFemaleGammaherpesvirinaeHerpesviridae InfectionsHerpesvirus 2, HumanHumansImmunizationInflammasomesIntercellular Signaling Peptides and ProteinsInterleukin-1betaLipopolysaccharidesMiceMice, Inbred C57BLMice, KnockoutPregnancyPremature BirthProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesConceptsFetal membranesViral infectionImmune responseTAM receptorsSubsequent preterm birthAdverse pregnancy outcomesIL-1β productionIL-1β responseHerpes viral infectionsInnate immune responseVivo mouse modelHuman fetal membranesAggravated inflammationIL-1β processingPregnancy outcomesPreterm birthAssociated complicationsPremature rupturePregnant womenLocal infectionInflammasome activationMerTK inhibitionMouse modelBacterial LPSLigand expression
2014
Toll‐like Receptor‐Mediated Responses by Placental Hofbauer Cells (HBCs): A Potential Pro‐Inflammatory Role for Fetal M2 Macrophages
Young OM, Tang Z, Niven‐Fairchild T, Tadesse S, Krikun G, Norwitz ER, Mor G, Abrahams VM, Guller S. Toll‐like Receptor‐Mediated Responses by Placental Hofbauer Cells (HBCs): A Potential Pro‐Inflammatory Role for Fetal M2 Macrophages. American Journal Of Reproductive Immunology 2014, 73: 22-35. PMID: 25345551, PMCID: PMC4268350, DOI: 10.1111/aji.12336.Peer-Reviewed Original ResearchConceptsHofbauer cellsHuman umbilical vein endothelial cellsM2 macrophagesTLR-3TLR-4Potential pro-inflammatory roleToll-like receptor functionPlacental villous coreAdverse pregnancy outcomesPro-inflammatory rolePlacental Hofbauer cellsIL-6 secretionToll-like receptorsPolycytidylic acid treatmentUmbilical vein endothelial cellsFetal inflammationPregnancy outcomesVein endothelial cellsTLR agonistsTLR-2Cytokine secretionInflammatory responseVillous corePlacental fibroblastsReceptor functionTrophoblast Induces Monocyte Differentiation Into CD14+/CD16+ Macrophages
Aldo PB, Racicot K, Craviero V, Guller S, Romero R, Mor G. Trophoblast Induces Monocyte Differentiation Into CD14+/CD16+ Macrophages. American Journal Of Reproductive Immunology 2014, 72: 270-284. PMID: 24995492, PMCID: PMC4230492, DOI: 10.1111/aji.12288.Peer-Reviewed Original ResearchConceptsUnique macrophage phenotypeMacrophage phenotypeMonocyte differentiationFirst trimester trophoblast cellsPeripheral blood monocytesPhenotype of macrophagesCD14 surface expressionNormal deciduaHealthy pregnancyIL-10Chemokine productionEarly pregnancyIP-10Monocyte exposureIL-1BBlood monocytesDecidual phenotypePhagocytic capacityTrophoblast cellsFlow cytometryMorphologic changesMacrophagesMonocytesSurface expressionPlacenta development
2013
Viral Infection of the Pregnant Cervix Predisposes to Ascending Bacterial Infection
Racicot K, Cardenas I, Wünsche V, Aldo P, Guller S, Means RE, Romero R, Mor G. Viral Infection of the Pregnant Cervix Predisposes to Ascending Bacterial Infection. The Journal Of Immunology 2013, 191: 934-941. PMID: 23752614, PMCID: PMC4153356, DOI: 10.4049/jimmunol.1300661.Peer-Reviewed Original ResearchConceptsFemale reproductive tractBacterial infectionsViral infectionLower female reproductive tractReproductive tractAntimicrobial peptide expressionProduction of mucusPreterm laborPreterm birthNeonatal mortalityUterine cavityUterine infectionMouse modelPeptide expressionInfectionCervixPolymicrobial diseaseMajor causeMultifactorial approachCommon routePregnancyBirthUterusTractAntimicrobial peptides
2012
Lipopolysaccharide Appears to Activate Human Endometrial Endothelial Cells Through TLR‐4‐Dependent and TLR‐4‐Independent Mechanisms
Krikun G, Trezza J, Shaw J, Rahman M, Guller S, Abrahams VM, Lockwood CJ. Lipopolysaccharide Appears to Activate Human Endometrial Endothelial Cells Through TLR‐4‐Dependent and TLR‐4‐Independent Mechanisms. American Journal Of Reproductive Immunology 2012, 68: 233-237. PMID: 22672000, PMCID: PMC3418410, DOI: 10.1111/j.1600-0897.2012.01164.x.Peer-Reviewed Original ResearchConceptsEndometrial endothelial cellsTissue factor expressionHuman endometrial endothelial cellsToll-like receptorsLPS-RSFactor expressionEndothelial cellsBacterial lipopolysaccharideTLR-4Innate immunityCytokine/chemokine responsesTLR-4 antagonistGram-negative bacterial lipopolysaccharideChemokine responsesIL-6IL-8Cytokine secretionG-CSFWestern blotLipopolysaccharideBacterial componentsCell-free supernatantMD-2ImmunitySecretion
2011
Hydroxychloroquine reduces binding of antiphospholipid antibodies to syncytiotrophoblasts and restores annexin A5 expression
Wu XX, Guller S, Rand JH. Hydroxychloroquine reduces binding of antiphospholipid antibodies to syncytiotrophoblasts and restores annexin A5 expression. American Journal Of Obstetrics And Gynecology 2011, 205: 576.e7-576.e14. PMID: 21871597, PMCID: PMC3224185, DOI: 10.1016/j.ajog.2011.06.064.Peer-Reviewed Original ResearchConceptsAntiphospholipid antibodiesHuman placental syncytiotrophoblastPlacental syncytiotrophoblastAnnexin A5 anticoagulant shieldA5 expressionEffect of hydroxychloroquineAnnexin A5 expressionFirst morphologic evidenceAntibody-mediated disruptionAntiphospholipid syndromeComputer-based morphometric analysisThrombogenic mechanismsBeWo trophoblastsImmune complexesNovel treatmentsHydroxychloroquineAntimalarial drugsImmunoglobulin G (IgG) bindingMorphologic evidenceSyncytiotrophoblastImmunoglobulin GsPrimary culturesAntibodiesAnnexin A5Laser confocal microscopy
2010
Focal Increases of Fetal Macrophages in Placentas from Pregnancies with Histological Chorioamnionitis: Potential Role of Fibroblast Monocyte Chemotactic Protein‐1
Toti P, Arcuri F, Tang Z, Schatz F, Zambrano E, Mor G, Niven‐Fairchild T, Abrahams VM, Krikun G, Lockwood CJ, Guller S. Focal Increases of Fetal Macrophages in Placentas from Pregnancies with Histological Chorioamnionitis: Potential Role of Fibroblast Monocyte Chemotactic Protein‐1. American Journal Of Reproductive Immunology 2010, 65: 470-479. PMID: 21087336, PMCID: PMC3071455, DOI: 10.1111/j.1600-0897.2010.00927.x.Peer-Reviewed Original ResearchConceptsHistopathological chorioamnionitisMCP-1 mRNAFocal increaseMonocyte chemotactic protein-1Subset of pregnanciesAdverse neonatal outcomesProtein expressionPro-inflammatory cytokinesMaternal-fetal interfaceChemotactic protein-1MCP-1 expressionTerm placental villiHistological chorioamnionitisNeonatal outcomesCytokine cascadeIL-1βInflammatory cytokinesQuantitative real-time PCRFetal monocytesReal-time PCRHuman term placental villiPlacental villiControl groupBacterial productsTreatment of fibroblastsProtein composition of microparticles shed from human placenta during placental perfusion: Potential role in angiogenesis and fibrinolysis in preeclampsia
Guller S, Tang Z, Ma YY, Di Santo S, Sager R, Schneider H. Protein composition of microparticles shed from human placenta during placental perfusion: Potential role in angiogenesis and fibrinolysis in preeclampsia. Placenta 2010, 32: 63-69. PMID: 21074265, PMCID: PMC3762591, DOI: 10.1016/j.placenta.2010.10.011.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitorMaternal perfusateSFlt-1Maternal endothelial cell dysfunctionFms-like tyrosine kinasePathophysiology of preeclampsiaMaternal-fetal interfaceEndothelial cell dysfunctionAnti-angiogenic actionFollowing relative levelsPlacental damagePlacental perfusionMaternal serumNormal pregnancyPlacental pathophysiologyAnnexin V bindingSyncytiotrophoblast microparticlesDual perfusionAngiogenic balanceCell dysfunctionMaternal bloodPreeclampsiaActivator inhibitorCytometric analysisLevel of expressionRole of GnRH–GnRH receptor signaling at the maternal-fetal interface
Lee HJ, Snegovskikh VV, Park JS, Foyouzi N, Han KT, Hodgson EJ, Guller S, Norwitz ER. Role of GnRH–GnRH receptor signaling at the maternal-fetal interface. Fertility And Sterility 2010, 94: 2680-2687. PMID: 20400076, DOI: 10.1016/j.fertnstert.2010.03.016.Peer-Reviewed Original ResearchConceptsGnRHR-I mRNAMaternal-fetal interfaceDecidual stromal cellsHCG productionGnRH-IISelect cytokinesTrophoblast cellsCell linesEffects of GnRHUniversity Teaching HospitalExpression of GnRHFunction of GnRHReverse transcription-polymerase chain reactionDose-dependent fashionHuman trophoblast cellsTerm deliveryPolymerase chain reactionTeaching hospitalGnRH receptorMAIN OUTCOMEGnRHHuman trophoblastsStromal cellsWestern blotImmortalized cell lines
2009
ORIGINAL ARTICLE: Regulation of Nod1 and Nod2 in First Trimester Trophoblast Cells
Mulla MJ, Yu AG, Cardenas I, Guller S, Panda B, Abrahams VM. ORIGINAL ARTICLE: Regulation of Nod1 and Nod2 in First Trimester Trophoblast Cells. American Journal Of Reproductive Immunology 2009, 61: 294-302. PMID: 19260860, DOI: 10.1111/j.1600-0897.2009.00694.x.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisBenzamidesCells, CulturedCytokinesDiaminopimelic AcidFemaleGene Expression Regulation, DevelopmentalHumansLipopolysaccharidesNF-kappa BNod1 Signaling Adaptor ProteinNod2 Signaling Adaptor ProteinPregnancyPregnancy Trimester, FirstSequence DeletionSignal TransductionThiazolesToll-Like Receptor 4TransgenesTrophoblastsConceptsFirst trimester trophoblast cellsTrophoblast cellsExpression of NOD1Cytoplasmic pattern recognition receptorsProduction of cytokinesNOD2 mRNA expressionPattern recognition receptorsNOD2 expressionCytokine responsesInflammatory responseNOD2 activationNOD1 activationNFkappaB inhibitorRecognition receptorsNOD1Nod1 stimulationNOD2Bacterial lipopolysaccharideMRNA expressionTLR4LipopolysaccharideNFkappaB pathwayRT-PCRBacterial peptidesTrophoblast
2008
Placental expression of ceruloplasmin in pregnancies complicated by severe preeclampsia
Guller S, Buhimschi CS, Y Y, Huang T, Yang L, Kuczynski E, Zambrano E, Lockwood CJ, Buhimschi IA. Placental expression of ceruloplasmin in pregnancies complicated by severe preeclampsia. Laboratory Investigation 2008, 88: 1057-1067. PMID: 18679377, PMCID: PMC2682720, DOI: 10.1038/labinvest.2008.74.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitor-1Severe preeclampsiaReperfusion injurySFlt-1Soluble fms-like tyrosine kinase-1Fms-like tyrosine kinase-1Ischemia/reperfusion injuryLife-threatening syndromeSubsequent reperfusion injuryTerm control groupPathophysiology of preeclampsiaTyrosine kinase-1Activator inhibitor-1Release of factorsSignificant increasePresence of mRNAUpregulation of mRNACeruloplasmin mRNAPlacental damagePlacental factorsMicroarray gene profilingEndothelium dysfunctionPE placentasQuantitative real-time PCRIntervillous space
2007
Expression of Toll-like receptors in the human decidua.
Krikun G, Lockwood CJ, Abrahams VM, Mor G, Paidas M, Guller S. Expression of Toll-like receptors in the human decidua. Histology And Histopathology 2007, 22: 847-54. PMID: 17503341, DOI: 10.14670/hh-22.847.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Vesicular TransportCells, CulturedDeciduaEndometriumEndothelial CellsFemaleHumansImmunity, InnateImmunohistochemistryInterleukinsLipopolysaccharidesMyeloid Differentiation Factor 88NF-kappa BPeptidoglycanPoly I-CPregnancyPregnancy Trimester, FirstPregnancy Trimester, ThirdReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSignal TransductionToll-Like ReceptorsConceptsToll-like receptorsHuman deciduaFirst trimester elective terminationMaternal spiral arteriesInnate immune responseCesarean sectionSpiral arteriesThird trimesterCytokine productionElective terminationDecidual tissuesImmune responseLate gestationPregnant endometriumFetal membranesSurveillance moleculeHost defensePregnancyDeciduaMRNA levelsReceptorsMicrobial pathogensTrimesterEndometriumArteryCell Type-specific Expression and Function of Toll-like Receptors 2 and 4 in Human Placenta: Implications in Fetal Infection
Ma Y, Krikun G, Abrahams VM, Mor G, Guller S. Cell Type-specific Expression and Function of Toll-like Receptors 2 and 4 in Human Placenta: Implications in Fetal Infection. Placenta 2007, 28: 1024-1031. PMID: 17588655, PMCID: PMC2064901, DOI: 10.1016/j.placenta.2007.05.003.Peer-Reviewed Original ResearchConceptsInnate immune responseIL-8 levelsToll-like receptorsTLR-4Immune responseTLR-2TLR functionTerm placentaToll-like receptor 2Endothelial cellsAdverse fetal outcomesTLR-2 expressionMaternal-fetal interfacePathogen-associated molecular patternsHuman term placentaCell type-specific expressionGram-negative bacterial lipopolysaccharideFetal outcomesPlacental infectionTLR expressionFetal infectionLPS treatmentMajor cell typesImmunohistochemical analysisStem villi
2006
Tumor Necrosis Factor-α and Interleukin-1β Regulate Interleukin-8 Expression in Third Trimester Decidual Cells Implications for the Genesis of Chorioamnionitis
Lockwood CJ, Arcuri F, Toti P, De Felice C, Krikun G, Guller S, Buchwalder LF, Schatz F. Tumor Necrosis Factor-α and Interleukin-1β Regulate Interleukin-8 Expression in Third Trimester Decidual Cells Implications for the Genesis of Chorioamnionitis. American Journal Of Pathology 2006, 169: 1294-1302. PMID: 17003486, PMCID: PMC1698845, DOI: 10.2353/ajpath.2006.060185.Peer-Reviewed Original ResearchConceptsTerm decidual cellsIL-8 expressionInterleukin-8 expressionTranscriptase-polymerase chain reactionDecidual cellsNeutrophil infiltrationIL-8TNF-alphaIL-8 secretion levelsIL-8 levelsIntense neutrophil infiltrationReverse transcriptase-polymerase chain reactionChain reactionInterleukin-1 betaTumor necrosis factorIL-8 mRNAEnzyme-linked immunosorbentIL-8 outputConcentration-response studiesNeutrophil infiltrateSteroidal milieuTerm deciduaTumor necrosisNecrosis factorImmunohistochemical staining
2005
Alterations in Syncytiotrophoblast Cytokine Expression Following Treatment with Lipopolysaccharide
Ma Y, Mor G, Abrahams VM, Buhimschi IA, Buhimschi CS, Guller S. Alterations in Syncytiotrophoblast Cytokine Expression Following Treatment with Lipopolysaccharide. American Journal Of Reproductive Immunology 2005, 55: 12-18. PMID: 16364007, DOI: 10.1111/j.1600-0897.2005.00347.x.Peer-Reviewed Original ResearchConceptsCytokine expressionLPS treatmentInflammatory compoundsAnti-inflammatory cytokinesIL-8 levelsInterleukin-8 levelsAnti-inflammatory compoundsEnzyme-linked immunosorbent assayCell typesCytokine levelsGlucocorticoid treatmentMaternal bloodDEX treatmentPlacental syncytiumSyncytiotrophoblastImmunosorbent assayLPSPrimary culturesTreatmentCytokinesFourfold increaseExpressionSyncytiaGestationLevelsExpression and Regulation of Glucocorticoid Receptor in Human Placental Villous Fibroblasts
Lee MJ, Wang Z, Yee H, Ma Y, Swenson N, Yang L, Kadner SS, Baergen RN, Logan SK, Garabedian MJ, Guller S. Expression and Regulation of Glucocorticoid Receptor in Human Placental Villous Fibroblasts. Endocrinology 2005, 146: 4619-4626. PMID: 16055431, DOI: 10.1210/en.2005-0235.Peer-Reviewed Original ResearchConceptsGC receptorSmooth muscle cellsHuman placentaGR levelsHormone treatmentShort-term GC treatmentMuscle cellsLong-term hormone treatmentVascular smooth muscle cellsGR protein expressionGR mRNA levelsPlacental cell typesNormal term human placentasTotal GR levelsTerm human placentaCell typesGR antibodyGC treatmentHormone exposureStem villiCytotrophoblast cellsGlucocorticoid receptorPlacental fibroblastsTerminal villiVillous fibroblasts
2004
Differential Effects of Lipopolysaccharide and Thrombin on Interleukin‐8 Expression in Syncytiotrophoblasts and Endothelial Cells: Implications for Fetal Survival
MA Y, KADNER SS, GULLER S. Differential Effects of Lipopolysaccharide and Thrombin on Interleukin‐8 Expression in Syncytiotrophoblasts and Endothelial Cells: Implications for Fetal Survival. Annals Of The New York Academy Of Sciences 2004, 1034: 236-244. PMID: 15731315, DOI: 10.1196/annals.1335.025.Peer-Reviewed Original ResearchConceptsCytokine expressionEndothelial cellsFetal survivalInfection-associated changesPlacental cytokine expressionTissue factor-initiated blood coagulationIL-8 levelsInterleukin-8 levelsAnti-inflammatory steroidsMaintenance of pregnancyIL-8 expressionIL-8 mRNAInterleukin-8 expressionEffect of thrombinHuman umbilical vein endothelial cellsHuman term placentaUmbilical vein endothelial cellsVein endothelial cellsCytokine responsesCytokine productionProinflammatory processesIL-8Inflammatory responseLPS treatmentIntervillous space