Seth Guller, PhD
Senior Research Scientist in Obstetrics, Gynecology, and Reproductive SciencesCards
About
Research
Overview
Medical Research Interests
Gynecology; Obstetrics; Placenta Diseases; Pre-Eclampsia; Pregnancy Outcome
Publications
2023
Leptin-Mediated Induction of IL-6 Expression in Hofbauer Cells Contributes to Preeclampsia Pathogenesis
Ozmen A, Nwabuobi C, Tang Z, Guo X, Larsen K, Guller S, Blas J, Moore M, Kayisli U, Lockwood C, Guzeloglu-Kayisli O. Leptin-Mediated Induction of IL-6 Expression in Hofbauer Cells Contributes to Preeclampsia Pathogenesis. International Journal Of Molecular Sciences 2023, 25: 135. PMID: 38203306, PMCID: PMC10778808, DOI: 10.3390/ijms25010135.Peer-Reviewed Original ResearchConceptsIL-6 expressionHofbauer cellsP65 NF-ĪŗBIL-6NF-ĪŗBLeptin levelsPreeclampsia pathogenesisElevated serum interleukin-6 levelsSerum interleukin-6 levelsERK1/2 MAPKInterleukin-6 levelsPro-inflammatory phenotypeAnti-inflammatory phenotypeLeptin receptor expressionIL-6 productionPathogenesis of PEPlacental leptin productionPhosphorylation levelsERK1/2 MAPK inhibitorIL-6 regulationConcentration-dependent mannerPE patientsHuman pregnancySecond trimesterLeptin concentrations
2022
Insulin increases placental triglyceride as a potential mechanism for fetal adiposity in maternal obesity
Anam AK, Cooke KM, Dratver MB, O'Bryan JV, Perley LE, Guller SM, Hwang JJ, Taylor HS, Goedeke L, Kliman HJ, Vatner DF, Flannery CA. Insulin increases placental triglyceride as a potential mechanism for fetal adiposity in maternal obesity. Molecular Metabolism 2022, 64: 101574. PMID: 35970449, PMCID: PMC9440306, DOI: 10.1016/j.molmet.2022.101574.Peer-Reviewed Original ResearchConceptsDe novo lipogenesisFetal adiposityFatty acid uptakeMaternal obesityObese womenNormal weightExcess adiposityVillous explantsInsulin receptorNewborns of mothersNormal-weight womenAcid uptakePlacental villous explantsTranscription factor SREBP-1Insulin-like growth factor 2Effect of insulinFatty acid oxidationPlacental triglyceridesPlacental responsesElevated triglyceridesMaternal hyperglycemiaWeight womenGrowth factor 2Diabetes riskPlacental metabolism
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 stateSyncytiaCellsVSVMaternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface
Lu-Culligan A, Chavan AR, Vijayakumar P, Irshaid L, Courchaine EM, Milano KM, Tang Z, Pope SD, Song E, Vogels CBF, Lu-Culligan WJ, Campbell KH, Casanovas-Massana A, Bermejo S, Toothaker JM, Lee HJ, Liu F, Schulz W, Fournier J, Muenker MC, Moore AJ, Team Y, Konnikova L, Neugebauer KM, Ring A, Grubaugh ND, Ko AI, Morotti R, Guller S, Kliman HJ, Iwasaki A, Farhadian SF. Maternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface. Med 2021, 2: 591-610.e10. PMID: 33969332, PMCID: PMC8084634, DOI: 10.1016/j.medj.2021.04.016.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionMaternal-fetal interfaceACE2 expressionNatural killerPregnant womenPlacental cellsAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSARS-CoV-2-infected womenTerm placentaSyndrome coronavirus 2 infectionCoronavirus 2 infectionPotential immune mechanismsRobust inflammatory responseRobust immune responseCoronavirus disease 2019Detectable viral RNAInterferon-related genesLower ACE2 expressionMajority of placentasPregnancy complicationsPlacental histologyHofbauer cellsEarly pregnancyImmune activation
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 studiesZika Virus-Infected Decidual Cells Elicit a Gestational Age-Dependent Innate Immune Response and Exaggerate Trophoblast Zika Permissiveness: Implication for Vertical Transmission.
Guzeloglu-Kayisli O, Guo X, Tang Z, Semerci N, Ozmen A, Larsen K, Mutluay D, Guller S, Schatz F, Kayisli UA, Lockwood CJ. Zika Virus-Infected Decidual Cells Elicit a Gestational Age-Dependent Innate Immune Response and Exaggerate Trophoblast Zika Permissiveness: Implication for Vertical Transmission. The Journal Of Immunology 2020, 205: 3083-3094. PMID: 33139490, DOI: 10.4049/jimmunol.2000713.Peer-Reviewed Original ResearchConceptsHuman decidual cellsDecidual cellsZika virusViral attachment factorsTerm decidual stromal cellsVertical transmissionDecidual cell supernatantsTerm decidual cellsInnate immune response genesInnate immune responsivenessExact pathogenic mechanismDecidual stromal cellsHuman first trimesterInnate immune responseSevere fetal defectsImmune response genesFetal sequelaeGestational ageFirst trimesterPlacental transmissionZIKV infectionCytotrophoblast culturesImmune responsivenessZika infectionLate pregnancyPeriāimplantation cytokine profile differs between singleton and twin IVF pregnancies
Simpson S, Kaislasuo J, Peng G, Aldo P, Paidas M, Guller S, Mor G, Pal L. Periāimplantation cytokine profile differs between singleton and twin IVF pregnancies. American Journal Of Reproductive Immunology 2020, 85: e13348. PMID: 32946159, PMCID: PMC8221280, DOI: 10.1111/aji.13348.Peer-Reviewed Original ResearchConceptsMaternal serum levelsSerum levelsSingleton gestationsIL-10Twin pregnanciesC motif chemokine ligand 10General immune reactionTwin IVF pregnanciesProspective longitudinal cohortSerum cytokine concentrationsAcademic fertility centerSerial serum samplesChemokine ligand 10Implantation phaseAnti-angiogenic roleSingleton conceptionsCXCL10 levelsIVF pregnanciesIVF-ETCytokine concentrationsInterleukin-10Fertility centerSerum concentrationsTumor necrosisLongitudinal cohortNLRP3 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-1Ī² processingIL-1Ī²Inflammasome activationFetal inflammatory response syndromeSubsequent pregnancy complicationsInflammatory response syndromeCell deathNLRP3 inflammasome activationInterleukin-1 betaIL-1Ī² secretionInhibition of P2X7Human term placentaGasdermin D cleavageNLRP3 knockdownPlacental inflammationPyroptotic cell deathFetal inflammationHistologic chorioamnionitisPregnancy complicationsResponse syndromeNLRP3 inflammasomeProtein/gene expressionInflammatory formTrophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function
Zhang Y, Aldo P, You Y, Ding J, Kaislasuo J, Petersen JF, Lokkegaard E, Peng G, Paidas MJ, Simpson S, Pal L, Guller S, Liu H, Liao AH, Mor G. Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function. Journal Of Leukocyte Biology 2020, 108: 983-998. PMID: 32386458, PMCID: PMC8190653, DOI: 10.1002/jlb.1a0420-012rr.Peer-Reviewed Original ResearchConceptsSoluble PD-L1Macrophage polarizationTrophoblast cellsCell death ligand 1PD-L1/PDPD-1 blockageDeath ligand 1Macrophage differentiationModulates macrophage polarizationExpression/secretionDecidual macrophagesHealthy pregnancyPD-L1Pregnant womenTLR4 ligationM2 phenotypeExpression of typeFetal developmentLPS activationMacrophagesIFNPlacenta developmentLigand 1Constitutive productionGestationHuman Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua
Silasi M, You Y, Simpson S, Kaislasuo J, Pal L, Guller S, Peng G, Ramhorst R, Grasso E, Etemad S, Durosier S, Aldo P, Mor G. Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua. Scientific Reports 2020, 10: 5785. PMID: 32238853, PMCID: PMC7113245, DOI: 10.1038/s41598-020-62593-9.Peer-Reviewed Original ResearchConceptsHuman chorionic gonadotropinCXCL10 expressionChorionic gonadotropinPotent immune-modulatory effectsImmune system undergoesImmune modulatory effectsEndometrial stromal cellsImmune cell recruitmentMaternal-fetal interfaceImmune regulatory functionsProcess of implantationCD8 cellsCytokine profilePregnancy progressesFetal interfaceDecidual samplesImmune populationsImmune factorsHuman deciduaT cellsDecidual cellsCell recruitmentModulatory effectsEarly hormoneStromal cells
News
News
- August 18, 2016
Yale study identifies how Zika virus infects the placenta
- August 18, 2016
Yale study identifies how Zika virus infects the placenta
- March 15, 2007
In Preeclampsia, Researchers Identify Proteins that Cause Blood Vessel Damage
- February 28, 2005
Proteins Found in Urine of Pregnant Women Could Help Diagnose Preeclampsia
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Obstetrics, Gynecology & Reproductive Sciences
333 Cedar Street
New Haven, CT 06510-
United States