Featured Publications
Combinatorial drug screening of mammary cells with induced mesenchymal transformation to identify drug combinations for triple-negative breast cancer
Colavito SA, Platt JT, Held MA, Liu Z, Sokup R, Stern DF. Combinatorial drug screening of mammary cells with induced mesenchymal transformation to identify drug combinations for triple-negative breast cancer. Oncotarget 2019, 10: 4822-4839. PMID: 31448050, PMCID: PMC6690678, DOI: 10.18632/oncotarget.27104.Peer-Reviewed Original ResearchBreast cancerDrug combinationsB-cell lymphoma-2 inhibitorTriple-negative breast cancerEffective treatment strategiesBreast cancer cellsEffective drug combinationsCombination regimenPoor prognosisCombination therapyTreatment optionsTreatment strategiesBCL2 inhibitorsEffective treatmentSelf-renewal capabilityCancerTumor cellsDifferent dosesCancer cellsMammary cellsCheckpoint kinase 1 inhibitorsKinase 1 inhibitorMesenchymal characteristicsMesenchymal transformationUntreated cellsNeuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake
Haskins JW, Zhang S, Means RE, Kelleher JK, Cline GW, Canfrán-Duque A, Suárez Y, Stern DF. Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake. Science Signaling 2015, 8: ra111. PMID: 26535009, PMCID: PMC4666504, DOI: 10.1126/scisignal.aac5124.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorCholesterolFemaleHumansHydroxymethylglutaryl CoA ReductasesLipoproteins, LDLMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesNeuregulin-1Proto-Oncogene Proteins c-aktReceptor, ErbB-4Receptors, LDLSterol Regulatory Element Binding Protein 2TOR Serine-Threonine KinasesConceptsIntracellular domainEGFR family membersLow-density lipoprotein uptakeCholesterol biosynthesisSREBP target genesRapamycin complex 1ErbB4 intracellular domainSite-1 proteaseCholesterol biosynthesis genesSoluble intracellular domainCholesterol biosynthetic pathwayActivation of ErbB4Mammary epithelial cellsInhibition of AktSterol regulatory elementBiosynthesis genesLipoprotein uptakeRegulatory elementsBiosynthetic pathwayTarget genesDevelopmental processesMetabolic remodelingMature formNeuregulin-1Cellular membranesPhosphoproteomic Screen Identifies Potential Therapeutic Targets in Melanoma
Tworkoski K, Singhal G, Szpakowski S, Zito CI, Bacchiocchi A, Muthusamy V, Bosenberg M, Krauthammer M, Halaban R, Stern DF. Phosphoproteomic Screen Identifies Potential Therapeutic Targets in Melanoma. Molecular Cancer Research 2011, 9: 801-812. PMID: 21521745, PMCID: PMC3117976, DOI: 10.1158/1541-7786.mcr-10-0512.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisCell Line, TumorCell MovementCell ProliferationErbB ReceptorsGene Expression Regulation, NeoplasticGene Knockdown TechniquesHEK293 CellsHumansInfant, NewbornMelanocytesMelanomaPhosphoproteinsPhosphorylationProteomicsReceptor Protein-Tyrosine KinasesReceptor, IGF Type 2RNA, Small InterferingSignal TransductionSkin NeoplasmsSTAT3 Transcription FactorConceptsTherapeutic targetReceptor tyrosine kinasesMelanoma cellsPotential therapeutic targetIdentifies potential therapeutic targetsActive receptor tyrosine kinasesTyrosine kinaseMelanoma cell migrationReceptor expressionBreast cancerAxl knockdownAutocrine circuitTherapeutic interventionsCancer subtypesReceptor tyrosine kinase activationTyrosine kinase activationNovel targetActivated receptorsAxlRNA knockdownMelanomaCell migrationHER3KnockdownIGF1RGenotype-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 mutationsMicrocephalin Is a DNA Damage Response Protein Involved in Regulation of CHK1 and BRCA1 * ♦
Xu X, Lee J, Stern DF. Microcephalin Is a DNA Damage Response Protein Involved in Regulation of CHK1 and BRCA1 * ♦. Journal Of Biological Chemistry 2004, 279: 34091-34094. PMID: 15220350, DOI: 10.1074/jbc.c400139200.Peer-Reviewed Original ResearchMeSH KeywordsBlotting, NorthernBlotting, WesternBRCA1 ProteinCell CycleCell Cycle ProteinsCell LineCheckpoint Kinase 1Cytoskeletal ProteinsDNADNA DamageDown-RegulationG2 PhaseGene Expression RegulationGene Expression Regulation, NeoplasticHistonesHumansMicroscopy, FluorescenceMitosisNerve Tissue ProteinsPhosphorylationPlasmidsPrecipitin TestsProtein KinasesProtein Structure, TertiaryRadiation, IonizingRNA, MessengerRNA, Small InterferingConceptsDNA damage-induced cellular responsesDNA damage response proteinsCellular responsesDamage response proteinsNFBD1/MDC1Regulation of BRCA1Regulation of Chk1Radiation-induced fociEndogenous BRCA1BRCT domainFirst geneResponse proteinsTranscript levelsMCPH1Primary microcephalyProteinMicrocephalinChk1Autosomal recessive diseaseBRCA1RegulationRecessive diseaseMDC1PtcbGenesErbB2 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 functionPolo-like Kinase 1 and Chk2 Interact and Co-localize to Centrosomes and the Midbody*
Tsvetkov L, Xu X, Li J, Stern DF. Polo-like Kinase 1 and Chk2 Interact and Co-localize to Centrosomes and the Midbody*. Journal Of Biological Chemistry 2002, 278: 8468-8475. PMID: 12493754, DOI: 10.1074/jbc.m211202200.Peer-Reviewed Original ResearchConceptsPhosphorylation of Chk2Polo-like kinase 1Thr-68DNA damageSimilar subcellular localization patternsDNA damage checkpoint pathwayKinase 1Damage checkpoint pathwaySubcellular localization patternsChromosome segregationMitotic exitLate mitosisNuclear fociMitotic entryIndirect immunofluorescence microscopyMitotic checkpointSer-28Early mitosisCheckpoint pathwayChk2Localization patternsCentrosomesThr-26Immunofluorescence microscopyMidbodyNFBD1/KIAA0170 Is a Chromatin-associated Protein Involved in DNA Damage Signaling Pathways*
Xu X, Stern DF. NFBD1/KIAA0170 Is a Chromatin-associated Protein Involved in DNA Damage Signaling Pathways*. Journal Of Biological Chemistry 2002, 278: 8795-8803. PMID: 12499369, DOI: 10.1074/jbc.m211392200.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceBase SequenceCell Cycle ProteinsChromatinDNA DamageDNA PrimersDNA ReplicationDNA-Binding ProteinsFluorescent Antibody Technique, IndirectG2 PhaseHeLa CellsHumansMitosisMolecular Sequence DataNuclear ProteinsPhosphorylationSequence Homology, Amino AcidSignal TransductionTrans-ActivatorsConceptsN-terminal FHA domainChromatin-associated proteinsDNA damageDNA Damage Signaling PathwayDNA double-strand breaksDiscrete nuclear fociDNA damage responseNumber of proteinsDouble-strand breaksBRCT domainFHA domainGamma-H2AX fociNuclear fociRad50 fociDamage responseDNA repairNFBD1Signaling pathwaysTandem repeatsProteinNuclear factorUntreated cellsHydroxyurea treatmentPathwayDiffuse nuclear stainingRad9 Phosphorylation Sites Couple Rad53 to the Saccharomyces cerevisiae DNA Damage Checkpoint
Schwartz MF, Duong JK, Sun Z, Morrow JS, Pradhan D, Stern DF. Rad9 Phosphorylation Sites Couple Rad53 to the Saccharomyces cerevisiae DNA Damage Checkpoint. Molecular Cell 2002, 9: 1055-1065. PMID: 12049741, DOI: 10.1016/s1097-2765(02)00532-4.Peer-Reviewed Original ResearchBinding SitesCell Cycle ProteinsCheckpoint Kinase 1Checkpoint Kinase 2DNA DamageForkhead Transcription FactorsMutationNuclear ProteinsPhosphorylationProtein KinasesProtein Serine-Threonine KinasesProtein Structure, TertiarySaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTranscription FactorsActivation 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 AlignmentSpecificity within the EGF family/ErbB receptor family signaling network
Riese D, Stern D. Specificity within the EGF family/ErbB receptor family signaling network. BioEssays 1998, 20: 41-48. PMID: 9504046, DOI: 10.1002/(sici)1521-1878(199801)20:1<41::aid-bies7>3.0.co;2-v.Peer-Reviewed Original ResearchConceptsErbB family receptorsFamily receptorsEpidermal growth factor (EGF) familyErbB receptor familyGrowth factor familyPeptide growth factorsReceptor couplingHormone-receptor interactionBiological responsesGrowth factorHormoneMultiple receptorsReceptorsReceptor familyCell proliferationErbB familyMultiple hormonesReceptor partnersTyrosine kinaseDiverse biological responsesActivation 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 phosphoproteinsPrognosisThe Cellular Response to Neuregulins Is Governed by Complex Interactions of the erbB Receptor Family
Riese D, van Raaij T, Plowman G, Andrews G, Stern D. The Cellular Response to Neuregulins Is Governed by Complex Interactions of the erbB Receptor Family. Molecular And Cellular Biology 1995, 15: 5770-5776. PMID: 7565730, PMCID: PMC230829, DOI: 10.1128/mcb.15.10.5770.Peer-Reviewed Original ResearchConceptsReceptor familyEpidermal growth factor receptor tyrosine kinase familyErbB family receptorsErbB receptor familyReceptor tyrosine kinase familyReceptor tyrosine phosphorylationPeptide agonistsFamily receptorsTyrosine kinase familyHuman cancersReceptor interactionEpidermal growth factor homology domainsCell linesCell survivalReceptorsNeuregulinCellular responsesTyrosine phosphorylationAntiserum 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 ResearchEGF‐stimulated tyrosine phosphorylation of p185neu: a potential model for receptor interactions.
Stern DF, Kamps MP. EGF‐stimulated tyrosine phosphorylation of p185neu: a potential model for receptor interactions. The EMBO Journal 1988, 7: 995-1001. PMID: 3261240, PMCID: PMC454426, DOI: 10.1002/j.1460-2075.1988.tb02906.x.Peer-Reviewed Original ResearchConceptsEGF-stimulated tyrosine phosphorylationTyrosine phosphorylationEGF receptorKinase activityReceptor-like proteinEGF receptor kinaseIntrinsic kinase activityRat-1 cellsTyrosine kinase activityEpidermal growth factor receptorReceptor kinaseGrowth factor receptorIncubation of cellsPhosphorylationEGFNeu/Factor receptorReceptor interactionSimilar kineticsGrowth factorP185ProteinP185neuReceptorsCellsp185, 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 factorP185ProteinReceptorsCoronavirus multiplication strategy. I. Identification and characterization of virus-specified RNA.
Stern DF, Kennedy SI. Coronavirus multiplication strategy. I. Identification and characterization of virus-specified RNA. Journal Of Virology 1980, 34: 665-74. PMID: 6247505, PMCID: PMC288755.Peer-Reviewed Original ResearchCoronavirus multiplication: locations of genes for virion proteins on the avian infectious bronchitis virus genome
Stern DF, Sefton BM. Coronavirus multiplication: locations of genes for virion proteins on the avian infectious bronchitis virus genome. Journal Of Virology 1984, 50: 22-29. PMID: 6321790, PMCID: PMC255576, DOI: 10.1128/jvi.50.1.22-29.1984.Peer-Reviewed Original ResearchConceptsVirion proteinsRNA AMessenger-dependent rabbit reticulocyte lysateTwo-dimensional tryptic peptide mappingPolypeptide of caSmall membrane proteinsLocation of genesAvian coronavirus infectious bronchitis virusNucleocapsid proteinRabbit reticulocyte lysateMajor virion proteinsCoronavirus infectious bronchitis virusCell-free translationInfectious bronchitis virus genomeSmall RNAsTryptic peptide mappingMembrane proteinsProtein p23Reticulocyte lysateSpecific mRNAsRNA CViral mRNAsCore polypeptidesMessenger activityVirus genome
2021
Treatment scheduling effects on the evolution of drug resistance in heterogeneous cancer cell populations
Patwardhan GA, Marczyk M, Wali VB, Stern DF, Pusztai L, Hatzis C. Treatment scheduling effects on the evolution of drug resistance in heterogeneous cancer cell populations. Npj Breast Cancer 2021, 7: 60. PMID: 34040000, PMCID: PMC8154902, DOI: 10.1038/s41523-021-00270-4.Peer-Reviewed Original ResearchHeterogeneous cancer cell populationsCancer cell populationsTriple-negative breast cancerSingle-cell RNA sequencingCell populationsFitness advantageRNA sequencingMDA-MB-231 TNBC cellsDrug resistanceMechanisms of resistanceVitro screening assaysClonal dynamicsTNBC cellsScreening assaysResistant clonesPatterns of resistanceConcomitant treatmentTherapy combinationsBreast cancerClinical studiesTreatment doseTreatment scheduleBarcodesSequencingTreatmentIdentifying modules of cooperating cancer drivers
Klein MI, Cannataro VL, Townsend JP, Newman S, Stern DF, Zhao H. Identifying modules of cooperating cancer drivers. Molecular Systems Biology 2021, 17: msb20209810. PMID: 33769711, PMCID: PMC7995435, DOI: 10.15252/msb.20209810.Peer-Reviewed Original ResearchConceptsCancer typesNRAS-mutant melanomaCombination of alterationsMultiple cancer typesClinical outcomesNFE2L2 mutationsIndividual patientsDriver alterationsEffective personalized treatmentPathway inhibitionTherapeutic potentialCancer etiologyPersonalized treatmentTumor formationTCGA cancer typesAlterationsPatientsCancer driversEtiologyMelanomaCancer