Featured Publications
Genotype-Selective Combination Therapies for Melanoma Identified by High-Throughput Drug Screening
Held MA, Langdon CG, Platt JT, Graham-Steed T, Liu Z, Chakraborty A, Bacchiocchi A, Koo A, Haskins JW, Bosenberg MW, Stern DF. Genotype-Selective Combination Therapies for Melanoma Identified by High-Throughput Drug Screening. Cancer Discovery 2013, 3: 52-67. PMID: 23239741, PMCID: PMC3546137, DOI: 10.1158/2159-8290.cd-12-0408.Peer-Reviewed Original ResearchConceptsMutant BRAF melanomaCyclin-dependent kinase inhibitorBRAF melanomaSmall molecule inhibitorsHigh-throughput drug screeningDrug screeningEGF receptorCombination therapyDrug combinationsMelanoma culturesContext of genotypePairwise combinationsResistance phenotypeCombinatorial drug screeningUnique treatment regimensCombination of statinsVivo xenograftsKinase inhibitorsMutant BRAFMutationsEfficacious drug combinationsPartial responseTreatment regimensRAS mutationsBRAF mutationsErbB2 is required for ductal morphogenesis of the mammary gland
Jackson-Fisher AJ, Bellinger G, Ramabhadran R, Morris JK, Lee KF, Stern DF. ErbB2 is required for ductal morphogenesis of the mammary gland. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 17138-17143. PMID: 15569931, PMCID: PMC535384, DOI: 10.1073/pnas.0407057101.Peer-Reviewed Original ResearchConceptsKinase geneNormal mouse mammary gland developmentReceptor kinase geneMammary budMouse mammary gland developmentReceptor tyrosine kinase geneTyrosine kinase geneMammary gland developmentMammary glandImportant normal functionsFunctions of ErbB2Gland developmentDuctal morphogenesisEpithelial treeLobuloalveolar developmentTerminal end budsLuminal spaceBudsGenesErbB2End budsHuman breast cancerAggressive phenotypeBreast cancerNormal functionActivation of Neu (ErbB-2) Mediated by Disulfide Bond-Induced Dimerization Reveals a Receptor Tyrosine Kinase Dimer Interface
Burke C, Stern D. Activation of Neu (ErbB-2) Mediated by Disulfide Bond-Induced Dimerization Reveals a Receptor Tyrosine Kinase Dimer Interface. Molecular And Cellular Biology 1998, 18: 5371-5379. PMID: 9710621, PMCID: PMC109122, DOI: 10.1128/mcb.18.9.5371.Peer-Reviewed Original Research3T3 CellsAmino Acid SequenceAmino Acid SubstitutionAnimalsCell LineCell Transformation, NeoplasticCOS CellsCysteineDimerizationDisulfidesDNA PrimersMiceModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedPolymerase Chain ReactionProtein Structure, SecondaryRatsReceptor Protein-Tyrosine KinasesReceptor, ErbB-2Recombinant ProteinsSequence AlignmentActivation state-specific monoclonal antibody detects tyrosine phosphorylated p185neu/erbB-2 in a subset of human breast tumors overexpressing this receptor.
DiGiovanna MP, Stern DF. Activation state-specific monoclonal antibody detects tyrosine phosphorylated p185neu/erbB-2 in a subset of human breast tumors overexpressing this receptor. Cancer Research 1995, 55: 1946-55. PMID: 7728765.Peer-Reviewed Original ResearchConceptsHuman breast tumorsBreast tumorsPrimary human breast tumorsPoor patient prognosisSubset of tumorsEpidermal growth factor receptorGrowth factor receptorPatient prognosisImmunohistochemical stainingNeu/ErbBTumor samplesTumorsMonoclonal antibodiesHuman tumorsFactor receptorRelated receptorsReceptorsP185Polyclonal antibodiesAntibodiesErbBRelated epidermal growth factor receptorSubsetTyrosine phosphoproteinsPrognosisAntiserum raised against a synthetic phosphotyrosine-containing peptide selectively recognizes p185neu/erbB-2 and the epidermal growth factor receptor.
Bangalore L, Tanner AJ, Laudano AP, Stern DF. Antiserum raised against a synthetic phosphotyrosine-containing peptide selectively recognizes p185neu/erbB-2 and the epidermal growth factor receptor. Proceedings Of The National Academy Of Sciences Of The United States Of America 1992, 89: 11637-11641. PMID: 1280833, PMCID: PMC50608, DOI: 10.1073/pnas.89.23.11637.Peer-Reviewed Original Researchp185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity.
Stern DF, Heffernan PA, Weinberg RA. p185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity. Molecular And Cellular Biology 1986, 6: 1729-1740. PMID: 2878363, PMCID: PMC367701, DOI: 10.1128/mcb.6.5.1729.Peer-Reviewed Original ResearchConceptsTyrosine kinase activityEGF receptorGrowth factor receptorProto-oncogeneKinase activityNeu proto-oncogeneC-erbB geneFactor receptorPresence of tunicamycinDistinct electrophoretic mobilitiesEpidermal growth factor receptorNormal culture conditionsMajor structural alterationsTyrosine phosphorylationGene productsNeu oncogeneNormal homologsOncogeneCell linesElectrophoretic mobilityCulture conditionsGrowth factorP185ProteinReceptors
2020
Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition
Gale M, Li Y, Cao J, Liu ZZ, Holmbeck MA, Zhang M, Lang SM, Wu L, Do Carmo M, Gupta S, Aoshima K, DiGiovanna MP, Stern DF, Rimm DL, Shadel GS, Chen X, Yan Q. Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition. Cancer Research 2020, 80: 524-535. PMID: 31690671, PMCID: PMC7002225, DOI: 10.1158/0008-5472.can-18-3985.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBreast NeoplasmsCell ProliferationDrug Resistance, NeoplasmEnzyme InhibitorsFemaleHumansMiceMice, Inbred NODMice, SCIDMitochondrial Proton-Translocating ATPasesOligomycinsReceptor, ErbB-2TrastuzumabTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsResistant cellsHER2-Targeted TherapyTrastuzumab-resistant tumorsNew therapeutic strategiesNovel potential targetDrug-free mediumAntibody therapySynthase inhibitionLow doseTherapeutic strategiesTrastuzumabBreast tumorsHER2TherapyAcquired ResistanceTumorsPotential targetMitochondrial respirationCellsSelective dependencyInhibitionMinimal changesNovel vulnerabilitiesATP synthase inhibitionOligomycin A
2017
Combinatorial Screening of Pancreatic Adenocarcinoma Reveals Sensitivity to Drug Combinations Including Bromodomain Inhibitor Plus Neddylation Inhibitor
Langdon CG, Platt JT, Means RE, Iyidogan P, Mamillapalli R, Klein M, Held MA, Lee JW, Koo JS, Hatzis C, Hochster HS, Stern DF. Combinatorial Screening of Pancreatic Adenocarcinoma Reveals Sensitivity to Drug Combinations Including Bromodomain Inhibitor Plus Neddylation Inhibitor. Molecular Cancer Therapeutics 2017, 16: 1041-1053. PMID: 28292938, PMCID: PMC5457712, DOI: 10.1158/1535-7163.mct-16-0794.Peer-Reviewed Original ResearchAdenosine TriphosphateAnimalsAntineoplastic AgentsApoptosisCarcinoma, Pancreatic DuctalCell Line, TumorCell ProliferationDNA DamageDose-Response Relationship, DrugDrug CombinationsDrug Screening Assays, AntitumorDrug SynergismHigh-Throughput Nucleotide SequencingHumansMiceMitochondriaMolecular Targeted TherapyNeoplastic Stem CellsPancreatic NeoplasmsSuperoxidesXenograft Model Antitumor Assays
2016
PMCA2 regulates HER2 protein kinase localization and signaling and promotes HER2-mediated breast cancer
Jeong J, VanHouten JN, Dann P, Kim W, Sullivan C, Yu H, Liotta L, Espina V, Stern DF, Friedman PA, Wysolmerski JJ. PMCA2 regulates HER2 protein kinase localization and signaling and promotes HER2-mediated breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e282-e290. PMID: 26729871, PMCID: PMC4725473, DOI: 10.1073/pnas.1516138113.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCalciumCarcinogenesisCell Line, TumorCell MembraneCell ProliferationCell SurvivalEndocytosisFemaleFluorescent Antibody TechniqueForkhead Box Protein O1Forkhead Transcription FactorsGene Knockdown TechniquesHSP90 Heat-Shock ProteinsHumansImmunoblottingIntracellular SpaceMammary Neoplasms, AnimalMicePlasma Membrane Calcium-Transporting ATPasesProtein BindingProtein TransportReceptor, ErbB-2Signal TransductionSurvival AnalysisConceptsBreast cancerHigh tumor levelsDegradation of HER2Increases Intracellular CalciumMouse mammary tumor virusBreast cancer cellsMammary tumor virusPMCA2 levelsNeu miceTumor levelsFormation of tumorsHER2 levelsIntracellular calciumTherapeutic targetBreast tumorsHER2Milk calciumExpression correlatesCancerHSP 90Mammary glandCancer cellsTumor virusTumorsCalcium
2014
Overexpression of ERBB4 JM-a CYT-1 and CYT-2 isoforms in transgenic mice reveals isoform-specific roles in mammary gland development and carcinogenesis
Wali VB, Gilmore-Hebert M, Mamillapalli R, Haskins JW, Kurppa KJ, Elenius K, Booth CJ, Stern DF. Overexpression of ERBB4 JM-a CYT-1 and CYT-2 isoforms in transgenic mice reveals isoform-specific roles in mammary gland development and carcinogenesis. Breast Cancer Research 2014, 16: 501. PMID: 25516216, PMCID: PMC4303208, DOI: 10.1186/s13058-014-0501-z.Peer-Reviewed Original ResearchConceptsTerminal end budsBreast cancerRole of ErbB4Transgenic miceCYT-2 isoformsMammary glandKi-67-positive cellsNeoplastic mammary lesionsIsoform-specific rolesBetter therapeutic strategiesMammary gland morphologyEpidermal growth factor receptorMammary terminal end budsMammary ductal morphogenesisErbB4 CYT-2Mammary gland developmentTumor suppressor roleGrowth factor receptorPotential oncogenic functionEarly pregnancyCarcinogenic changesNovel oncogenic propertiesMammary lesionsWhole mount analysisErbB4 expression
2013
EGF Receptor Activates MET through MAPK to Enhance Non–Small Cell Lung Carcinoma Invasion and Brain Metastasis
Breindel JL, Haskins JW, Cowell EP, Zhao M, Nguyen DX, Stern DF. EGF Receptor Activates MET through MAPK to Enhance Non–Small Cell Lung Carcinoma Invasion and Brain Metastasis. Cancer Research 2013, 73: 5053-5065. PMID: 23794705, PMCID: PMC3745527, DOI: 10.1158/0008-5472.can-12-3775.Peer-Reviewed Original ResearchConceptsNon-small cell lung carcinomaMitogen-activated protein kinaseBrain metastasesEGFR-METMET activationMutant EGFRCell lung carcinomaEffect of MetSMET kinase inhibitorEGF receptorErbB family membersMET amplificationLung carcinomaDrug treatmentTherapeutic targetEGFRMet levelsDrug resistanceCell subpopulationsCarcinoma invasionKinase inhibitorsMET phosphorylationProtein levelsMetSContinued investigation
2011
NFBD1/MDC1 Regulates Cav1 and Cav2 Independently of DNA Damage and p53
Wilson KA, Colavito SA, Schulz V, Wakefield PH, Sessa W, Tuck D, Stern DF. NFBD1/MDC1 Regulates Cav1 and Cav2 Independently of DNA Damage and p53. Molecular Cancer Research 2011, 9: 766-781. PMID: 21551225, PMCID: PMC3901581, DOI: 10.1158/1541-7786.mcr-10-0317.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAtaxia Telangiectasia Mutated ProteinsCaveolin 1Caveolin 2Cell AdhesionCell Cycle ProteinsCell Line, TumorCells, CulturedChromatinDNA DamageDNA RepairDNA-Binding ProteinsFibroblastsGene Knockdown TechniquesHistonesHumansMiceNuclear ProteinsProtein Serine-Threonine KinasesRNA, MessengerSignal TransductionTrans-ActivatorsTranscription, GeneticTumor Suppressor Protein p53Tumor Suppressor ProteinsConceptsDNA damage checkpoint signalingNFBD1 knockdownDNA damageNFBD1/MDC1Focal adhesion signalingDNA repair factorsDNA damage responseP53-mediated transcriptionAdhesion signalingCheckpoint signalingRepair factorsResponsive transcriptionDamage responseMitogenic signalingNFBD1DNA repairNovel functionTransactivation activityGene pathwaysAtaxia telangiectasiaMicroarray analysisSimilar phenotypeERK phosphorylationGenesTranscription
2008
ErbB3 is required for ductal morphogenesis in the mouse mammary gland
Jackson-Fisher AJ, Bellinger G, Breindel JL, Tavassoli FA, Booth CJ, Duong JK, Stern DF. ErbB3 is required for ductal morphogenesis in the mouse mammary gland. Breast Cancer Research 2008, 10: r96. PMID: 19019207, PMCID: PMC2656891, DOI: 10.1186/bcr2198.Peer-Reviewed Original ResearchConceptsTerminal end budsMammary fat padEnd budsMammary budBreast cancerFat padDuctal outgrowthMammary glandHER2/neuHuman breast cancerSmooth muscle actinNormal mammary glandSections of glandsMammary ductal treeMouse mammary gland developmentMammary gland developmentErbB3 functionMouse mammary glandRole of ErbB3Lobuloalveolar developmentEpithelial areaErbB2/HER2/NeuPredictive valueMuscle actinTherapeutic resistanceERBB3/HER3 and ERBB2/HER2 Duet in Mammary Development and Breast Cancer
Stern DF. ERBB3/HER3 and ERBB2/HER2 Duet in Mammary Development and Breast Cancer. Journal Of Mammary Gland Biology And Neoplasia 2008, 13: 215. PMID: 18454306, PMCID: PMC6590701, DOI: 10.1007/s10911-008-9083-7.Peer-Reviewed Original ResearchConceptsBreast cancerCancer etiologyErbB3/HER3Breast cancer etiologyAdditional therapeutic opportunitiesEpidermal growth factor receptor familyGrowth factor receptor familyAkt-dependent pathwayFactor receptor familyMouse modelERBB2 amplificationNeuregulin-2Neuregulin-1Therapeutic opportunitiesTherapeutic toolMammary developmentRegulation of metabolismCancerReceptor familyAggressive propertiesTherapeutic compoundsErbB2ErbB3Eventual developmentEtiology
2006
Formation of Neu/ErbB2-induced mammary tumors is unaffected by loss of ErbB4
Jackson-Fisher AJ, Bellinger G, Shum E, Duong JK, Perkins AS, Gassmann M, Muller W, Kent Lloyd KC, Stern DF. Formation of Neu/ErbB2-induced mammary tumors is unaffected by loss of ErbB4. Oncogene 2006, 25: 5664-5672. PMID: 16652155, DOI: 10.1038/sj.onc.1209574.Peer-Reviewed Original ResearchConceptsClinical studiesMammary tumorsMammary glandSimilar latency periodHistology of tumorsLoss of ERBB4Epidermal growth factor receptorTumor suppressorGrowth factor receptorLung metastasesBreast cancerErbb4 allelesMMTV-NeuLatency periodNull miceTumorsReceptor tyrosine kinasesFactor receptorErbB4ErbB familyCancerMiceTyrosine kinaseTissue culture analysisGland
2003
Neural and mammary gland defects in ErbB4 knockout mice genetically rescued from embryonic lethality
Tidcombe H, Jackson-Fisher A, Mathers K, Stern DF, Gassmann M, Golding JP. Neural and mammary gland defects in ErbB4 knockout mice genetically rescued from embryonic lethality. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 8281-8286. PMID: 12824469, PMCID: PMC166220, DOI: 10.1073/pnas.1436402100.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell MovementCentral Nervous SystemCerebellumCranial NervesDNA, ComplementaryDNA-Binding ProteinsEmbryonic and Fetal DevelopmentErbB ReceptorsFemaleFetal HeartInterneuronsLactationMaleMammary Glands, AnimalMiceMice, KnockoutMice, TransgenicMilk ProteinsMorphogenesisMyosinsNeural CrestNeuromuscular JunctionOrgan SpecificityPhosphorylationPhrenic NervePregnancyPromoter Regions, GeneticProtein Processing, Post-TranslationalReceptor, ErbB-4STAT5 Transcription FactorTrans-ActivatorsTransgenesErbBs in mammary development
Stern DF. ErbBs in mammary development. Experimental Cell Research 2003, 284: 89-98. PMID: 12648468, DOI: 10.1016/s0014-4827(02)00103-9.Peer-Reviewed Original ResearchConceptsMammary developmentHuman mammary carcinomaCancer therapyHER2/neuNormal mammary developmentEpidermal growth factor receptorGrowth factor receptorMammary carcinomaBreast cancerErbB2/HER2/NeuRational targetReceptor tyrosine kinasesFactor receptorReceptorsErbB familyTherapyTyrosine kinaseFrequent selectionErbBCarcinomaEtiologyCancerMiceNeu
1999
Neuregulin activation of ErbB receptors in vascular endothelium leads to angiogenesis
Russell K, Stern D, Polverini P, Bender J. Neuregulin activation of ErbB receptors in vascular endothelium leads to angiogenesis. American Journal Of Physiology 1999, 277: h2205-h2211. PMID: 10600838, DOI: 10.1152/ajpheart.1999.277.6.h2205.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCorneaEndothelial Growth FactorsEndothelium, VascularErbB ReceptorsHumansLymphokinesMiceNeovascularization, PhysiologicNeuregulinsRatsReceptor, ErbB-2Receptor, ErbB-3Receptor, ErbB-4ThrombinUmbilical VeinsVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsHuman umbilical vein endothelial cellsVascular endotheliumErbB receptorsReceptor tyrosine phosphorylationStimulation of HUVECsRapid calcium fluxReceptor family membersEndothelial cell growth factorTransmembrane tyrosine kinase receptorVascular endothelial cell growth factorEndothelial cell signalingReceptor-ligand interactionsTyrosine kinase receptorsEpidermal growth factor receptorVascular endothelial growthCell growth factorUmbilical vein endothelial cellsCell signalingGrowth factor receptorTyrosine phosphorylationVivo angiogenic responseExpression patternsGrowth regulationVein endothelial cellsIntracellular signalingErbb4 Signaling in the Mammary Gland Is Required for Lobuloalveolar Development and Stat5 Activation during Lactation
Jones F, Welte T, Fu X, Stern D. Erbb4 Signaling in the Mammary Gland Is Required for Lobuloalveolar Development and Stat5 Activation during Lactation. Journal Of Cell Biology 1999, 147: 77-88. PMID: 10508857, PMCID: PMC2164978, DOI: 10.1083/jcb.147.1.77.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCell NucleusDNA-Binding ProteinsErbB ReceptorsFemaleGene Expression Regulation, DevelopmentalHumansLactationMammary Glands, AnimalMiceMice, TransgenicMilk ProteinsPhosphorylationPrecipitin TestsPregnancyReceptor, ErbB-4RNA, MessengerSequence DeletionSignal TransductionSrc Homology DomainsSTAT5 Transcription FactorTrans-ActivatorsTransgenesConceptsFunction of ErbB4Dominant-negative alleleMammary glandAlpha-lactalbumin mRNAEpidermal growth factor receptor familyBeta-casein mRNAGrowth factor receptor familyNormal mouse mammary glandMouse mammary glandSH2 domainFactor receptor familyTerminal differentiationProtein mRNAReceptor familyLobuloalveolar developmentAcidic protein mRNASitu hybridizationMammary developmentPhosphorylationErbB4MRNALobuloalveoliUnique responseExpressionImportant roleExpression of dominant-negative ErbB2 in the mammary gland of transgenic mice reveals a role in lobuloalveolar development and lactation
Jones F, Stern D. Expression of dominant-negative ErbB2 in the mammary gland of transgenic mice reveals a role in lobuloalveolar development and lactation. Oncogene 1999, 18: 3481-3490. PMID: 10376526, DOI: 10.1038/sj.onc.1202698.Peer-Reviewed Original ResearchConceptsNormal mouse mammary gland developmentDominant-negative alleleMouse mammary gland developmentMammary glandErbB2/HER2/NeuMammary gland developmentMouse mammary glandNegative allelesFunctions of ErbB2ErbB2 signalingGland developmentLobuloalveolar developmentMammary developmentProtein expressionHuman breast cancerErbB2Transgenic miceExpressionPhenotypeLobuloalveoliSignalingOverexpression