2024
Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract
Mao T, Kim J, Peña-Hernández M, Valle G, Moriyama M, Luyten S, Ott I, Gomez-Calvo M, Gehlhausen J, Baker E, Israelow B, Slade M, Sharma L, Liu W, Ryu C, Korde A, Lee C, Monteiro V, Lucas C, Dong H, Yang Y, Initiative Y, Gopinath S, Wilen C, Palm N, Dela Cruz C, Iwasaki A, Vogels C, Hahn A, Chen N, Breban M, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Grubaugh N. Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2319566121. PMID: 38648490, PMCID: PMC11067057, DOI: 10.1073/pnas.2319566121.Peer-Reviewed Original ResearchConceptsInterferon-stimulated genesRespiratory infectionsStrains of influenza A virusTreatment of respiratory viral infectionsRespiratory virus infectionsInfluenza A virusMouse model of COVID-19Respiratory viral infectionsNeomycin treatmentExpression of interferon-stimulated genesUpper respiratory infectionInterferon-stimulated gene expressionLower respiratory infectionsBroad spectrum of diseasesAdministration of neomycinRespiratory viral diseasesDisease to patientsUpper respiratory tractIntranasal deliveryCongenic miceIntranasal applicationNasal mucosaSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2A virusThe chemokine receptor CXCR3 promotes CD8+ T cell–dependent lung pathology during influenza pathogenesis
Guo K, Yombo D, Wang Z, Navaeiseddighi Z, Xu J, Schmit T, Ahamad N, Tripathi J, De Kumar B, Mathur R, Hur J, Sun J, Olszewski M, Khan N. The chemokine receptor CXCR3 promotes CD8+ T cell–dependent lung pathology during influenza pathogenesis. Science Advances 2024, 10: eadj1120. PMID: 38170765, PMCID: PMC10776024, DOI: 10.1126/sciadv.adj1120.Peer-Reviewed Original ResearchConceptsLung pathologyT cellsLung injuryCytotoxic responsePeak viral loadChemokine receptor CXCR3Wild-type CD8Robust cytotoxic responseSingle-cell RNA sequencing analysisCXCR3 blockadeAdoptive transferEffector potentialT subpopulationsT effectorsViral clearanceViral loadEffector subsetsReceptor CXCR3Influenza pathogenesisCD8Therapeutic effectMurine lungInfluenza controlCentral memoryCXCR3
2023
Shared retinoic acid responsive enhancers coordinately regulate nascent transcription of Hoxb coding and non-coding RNAs in the developing mouse neural tube
Afzal Z, Lange J, Nolte C, McKinney S, Wood C, Paulson A, De Kumar B, Unruh J, Slaughter B, Krumlauf R. Shared retinoic acid responsive enhancers coordinately regulate nascent transcription of Hoxb coding and non-coding RNAs in the developing mouse neural tube. Development 2023, 150: dev201259. PMID: 37102683, PMCID: PMC10233718, DOI: 10.1242/dev.201259.Peer-Reviewed Original ResearchConceptsNascent transcriptionDynamic regulatory interactionsHox gene expressionCis-regulatory elementsRetinoic acid response elementMouse neural tubeTranscription of genesNon-coding RNAAcid response elementSingle-molecule fluorescentRetinoic acid responseMutant embryosHOXB clusterHox expressionAxial identityHoxb genesRegulatory interactionsTranscriptional mechanismsGene expressionDependent enhancersTranscriptionResponse elementResponsive enhancerNeural tubeCompetitive interactions
2021
Autocrine GMCSF Signaling Contributes to Growth of HER2+ Breast Leptomeningeal CarcinomatosisGMCSF Contributes to Breast Leptomeningeal Carcinomatosis
Ansari K, Bhan A, Saotome M, Tyagi A, De Kumar B, Chen C, Takaku M, Jandial R. Autocrine GMCSF Signaling Contributes to Growth of HER2+ Breast Leptomeningeal CarcinomatosisGMCSF Contributes to Breast Leptomeningeal Carcinomatosis. Cancer Research 2021, 81: 4723-4735. PMID: 34247146, PMCID: PMC8986153, DOI: 10.1158/0008-5472.can-21-0259.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutocrine CommunicationBreast NeoplasmsCell Line, TumorCell ProliferationCell SurvivalDisease Models, AnimalGene ExpressionGranulocyte-Macrophage Colony-Stimulating FactorHumansMeningeal CarcinomatosisMiceOncogene ProteinsProtein Kinase InhibitorsReceptor, ErbB-2Signal TransductionXenograft Model Antitumor AssaysConceptsOligodendrocyte progenitor cellsLeptomeningeal carcinomatosisLC growthPan-Aurora kinase inhibitorKinase inhibitorsSuppression of HER2Growth of HER2Central nervous system cell typesProliferation of HER2Nervous system cell typesBreast cancer cellsPrimary HER2Targetable axisOminous complicationIntrathecal deliveryMolecular mechanismsTreatment optionsDire prognosisSpinal cordBreast cancerHER2LC developmentLeptomeningesLC/MS-MSCarcinomatosis
2020
A six-amino-acid motif is a major determinant in functional evolution of HOX1 proteins
Singh N, De Kumar B, Paulson A, Parrish M, Zhang Y, Florens L, Conaway J, Si K, Krumlauf R. A six-amino-acid motif is a major determinant in functional evolution of HOX1 proteins. Genes & Development 2020, 34: 1680-1696. PMID: 33184220, PMCID: PMC7706710, DOI: 10.1101/gad.342329.120.Peer-Reviewed Original ResearchConceptsC-terminal motifAncestral activityFunctional analysisDNA-binding patternsGenome-wide analysisDNA-binding regionLow sequence similarityDNA-binding experimentsAmino acid sequenceSix-amino acid motifAncestral functionPbx proteinsEvolutionary noveltyGene duplicationFunctional diversificationHoxa1 proteinMouse proteinProtein functionSequence similarityFunctional evolutionAcid sequenceChimeric proteinMouse cellsHoxb1Structural predictions
2019
A Hox-TALE regulatory circuit for neural crest patterning is conserved across vertebrates
Parker H, De Kumar B, Green S, Prummel K, Hess C, Kaufman C, Mosimann C, Wiedemann L, Bronner M, Krumlauf R. A Hox-TALE regulatory circuit for neural crest patterning is conserved across vertebrates. Nature Communications 2019, 10: 1189. PMID: 30867425, PMCID: PMC6416258, DOI: 10.1038/s41467-019-09197-8.Peer-Reviewed Original ResearchConceptsNeural crestHox genesAncestral mechanismRegulatory circuitsUpstream regulatory componentsNeural crest patterningAncient paraloguesPbx proteinsJawed vertebratesAncient conservationExtant vertebratesAncestral activityRegulatory interactionsHOX2 genesRegulatory componentsVertebratesJaw formationGenesGnathostomesEnhancerHoxLampreyParaloguesImportant roleHoxa2
2018
Retinoid-Sensitive Epigenetic Regulation of the Hoxb Cluster Maintains Normal Hematopoiesis and Inhibits Leukemogenesis
Qian P, De Kumar B, He X, Nolte C, Gogol M, Ahn Y, Chen S, Li Z, Xu H, Perry J, Hu D, Tao F, Zhao M, Han Y, Hall K, Peak A, Paulson A, Zhao C, Venkatraman A, Box A, Perera A, Haug J, Parmely T, Li H, Krumlauf R, Li L. Retinoid-Sensitive Epigenetic Regulation of the Hoxb Cluster Maintains Normal Hematopoiesis and Inhibits Leukemogenesis. Cell Stem Cell 2018, 22: 740-754.e7. PMID: 29727682, DOI: 10.1016/j.stem.2018.04.012.Peer-Reviewed Original ResearchConceptsHoxb expressionHematopoietic stem cellsDNA methylationCoordinate regulationLoss of HSCsCis-regulatory elementsSpecific DNA methylationDNA methylome analysisHox genesHOXB clusterHox expressionEpigenetic regulationDNA methyltransferasesMethylome analysisHoxb genesCluster expressionLT-HSCsRetinoid signalingNormal hematopoiesisGenesStem cellsLeukemogenesisMethylationReconstitution capacityRegulation
2017
Hoxa1 targets signaling pathways during neural differentiation of ES cells and mouse embryogenesis
De Kumar B, Parker H, Paulson A, Parrish M, Zeitlinger J, Krumlauf R. Hoxa1 targets signaling pathways during neural differentiation of ES cells and mouse embryogenesis. Developmental Biology 2017, 432: 151-164. PMID: 28982536, DOI: 10.1016/j.ydbio.2017.09.033.Peer-Reviewed Original ResearchConceptsTarget genesEar developmentES cellsDifferential gene expression analysisGenome-wide analysisNeural crest specificationFunctional rolePutative target genesTransgenic mouse embryosMajor signaling pathwaysNeural crest migrationRelevant target genesDown-stream componentsMouse ES cellsGene expression analysisImportant functional roleRetinoic acidEvolutionary conservationEpigenetic marksHox cofactorsMutant phenotypeMouse embryogenesisNearby genesNeural fateMouse developmentHOXA1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on HOXA1 targets
De Kumar B, Parker H, Paulson A, Parrish M, Pushel I, Singh N, Zhang Y, Slaughter B, Unruh J, Florens L, Zeitlinger J, Krumlauf R. HOXA1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on HOXA1 targets. Genome Research 2017, 27: 1501-1512. PMID: 28784834, PMCID: PMC5580710, DOI: 10.1101/gr.219386.116.Peer-Reviewed Original ResearchConceptsCross-regulatory interactionsTALE proteinsTALE membersCombinatorial binding patternsGenome-wide analysisGenome-wide basisCross-regulatory networkDiverse functional rolesMouse ES cellsHox cofactorsTALE familyFunctional diversityTransgenic reporterCombinatorial interactionsRegulatory networksHox-PbxProteomic analysisEnhancer activityHOXA1ES cellsFunctional roleProteinDistinct mechanismsBinding patternDistinct classesDynamic regulation of Nanog and stem cell-signaling pathways by Hoxa1 during early neuro-ectodermal differentiation of ES cells
De Kumar B, Parker H, Parrish M, Lange J, Slaughter B, Unruh J, Paulson A, Krumlauf R. Dynamic regulation of Nanog and stem cell-signaling pathways by Hoxa1 during early neuro-ectodermal differentiation of ES cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 5838-5845. PMID: 28584089, PMCID: PMC5468655, DOI: 10.1073/pnas.1610612114.Peer-Reviewed Original ResearchConceptsES cell differentiationRegulatory networksMutual repressionRegulatory regionsCell differentiationCore pluripotency networkGenome-wide mappingRegulation of pluripotencyPatterns of occupancyCell-signaling pathwaysPluripotency networkNanog bindsHox genesGenomic approachesCommon target sitesRetinoic acid treatmentTarget genesDynamic regulationES cellsMouse embryosMolecular mechanismsHOXA1GenesAlternate statesNanog
2015
Analysis of dynamic changes in retinoid-induced transcription and epigenetic profiles of murine Hox clusters in ES cells
De Kumar B, Parrish M, Slaughter B, Unruh J, Gogol M, Seidel C, Paulson A, Li H, Gaudenz K, Peak A, McDowell W, Fleharty B, Ahn Y, Lin C, Smith E, Shilatifard A, Krumlauf R. Analysis of dynamic changes in retinoid-induced transcription and epigenetic profiles of murine Hox clusters in ES cells. Genome Research 2015, 25: 1229-1243. PMID: 26025802, PMCID: PMC4510006, DOI: 10.1101/gr.184978.114.Peer-Reviewed Original ResearchConceptsChromatin modificationsHomeotic clustersHox genesES cellsClustered Hox genesHomeotic gene transcriptionMouse embryonic stem cellsNoncoding RNA genesRetinoid-induced transcriptionGenome-wide approachesCis-regulatory elementsEmbryonic stem cellsTranscription stateChromatin marksHOXB clusterNoncoding genesRNA genesSegmental identityActive transcriptionNoncoding RNAsTranscription factorsEpigenetic profilesGene transcriptionEpigenetic changesBody axis
2014
Hox Complex Analysis Through BAC Recombineering
Parrish M, Ahn Y, Nolte C, De Kumar B, Krumlauf R. Hox Complex Analysis Through BAC Recombineering. Methods In Molecular Biology 2014, 1196: 59-87. PMID: 25151158, DOI: 10.1007/978-1-4939-1242-1_5.Peer-Reviewed Original Research
2012
Poised RNA Polymerase II Changes over Developmental Time and Prepares Genes for Future Expression
Gaertner B, Johnston J, Chen K, Wallaschek N, Paulson A, Garruss A, Gaudenz K, De Kumar B, Krumlauf R, Zeitlinger J. Poised RNA Polymerase II Changes over Developmental Time and Prepares Genes for Future Expression. Cell Reports 2012, 2: 1670-1683. PMID: 23260668, PMCID: PMC3572839, DOI: 10.1016/j.celrep.2012.11.024.Peer-Reviewed Original ResearchConceptsPol IIMammalian embryonic stem cellsGenes de novoDevelopmental control genesPolycomb group repressionFuture gene expressionRNA Pol IIRNA polymerase IIEmbryonic stem cellsTissue-specific fashionChromatin stateDrosophila embryosPolymerase IIExtracellular signalsDevelopmental programStages of differentiationGene expressionControl genesDevelopmental timeSynchronous inductionDynamic expressionGenesStem cellsDe novoFuture expression
2011
Dynamic transcriptional events in embryonic stem cells mediated by the super elongation complex (SEC)
Lin C, Garrett A, De Kumar B, Smith E, Gogol M, Seidel C, Krumlauf R, Shilatifard A. Dynamic transcriptional events in embryonic stem cells mediated by the super elongation complex (SEC). Genes & Development 2011, 25: 1486-1498. PMID: 21764852, PMCID: PMC3143939, DOI: 10.1101/gad.2059211.Peer-Reviewed Original ResearchConceptsSuper elongation complexEmbryonic stem cellsElongation complexPol IIDifferentiation signalsDynamic transcriptional eventsMurine embryonic stem cellsRNA polymerase IIStem cellsGlobal genomic analysisTranscription elongationPolymerase IITranscriptional regulationTranscriptional activationTranscriptional eventsGenomic analysisEnvironmental cuesES cellsGene expressionHuman cellsEnvironmental stimuliGenesEssential roleActivation signalsMajor classes