David F. Stern, PhD
Professor of PathologyCards
Appointments
Additional Titles
Vice Chair for Basic and Translational Sciences, Pathology
Associate Cancer Center Director, Shared Resources
Contact Info
Appointments
Additional Titles
Vice Chair for Basic and Translational Sciences, Pathology
Associate Cancer Center Director, Shared Resources
Contact Info
Appointments
Additional Titles
Vice Chair for Basic and Translational Sciences, Pathology
Associate Cancer Center Director, Shared Resources
Contact Info
About
Titles
Professor of Pathology
Vice Chair for Basic and Translational Sciences, Pathology; Associate Cancer Center Director, Shared Resources
Biography
Dr. Stern earned a BS in Biology at MIT in 1976. He received a PhD in Biology in 1983 at University of California, San Diego, and the Salk Institute with S.I.T. Kennedy and Bart Sefton for dissertation research that elucidated the coronavirus lytic cycle. Dr. Stern returned to R.A. Weinberg’s lab at the MIT Cancer Center and Whitehead Institute for Biomedical Research in 1983. There, Dr. Stern’s postdoctoral work pioneered analysis of neu/ErbB2/HER2, an important human oncogene. As a Yale Pathology faculty member since 1988, Dr. Stern’s research has focused on the roles of eleven growth factors and four receptors of the EGF family in malignant transformation, especially in breast cancer, and he has also made significant contributions to the understanding of DNA damage response signaling pathways. Dr. Stern’s current work in breast cancer and melanoma includes developing approaches to countering rapid resistance to anti-cancer agents that target cancer signaling pathways. Dr. Stern is active in cancer training at Yale and in the Yale Cancer Center scientific leadership. He is Associate Director of Shared Resources at Yale Cancer Center.
Appointments
Pathology
ProfessorPrimary
Other Departments & Organizations
- Cancer Signaling Networks
- Computational Biology and Biomedical Informatics
- Dean's Workshops
- K12 Calabresi Immuno-Oncology Training Program (IOTP)
- Molecular Medicine, Pharmacology, and Physiology
- Pathology
- Pathology and Molecular Medicine
- Pathology Research
- SPORE in Skin Cancer
- Stern Lab
- Yale Cancer Center
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
Education & Training
- Postdoctoral Fellow
- Whitehead Institute for Biomedical Research at Mass. Institute of Technology (1988)
- PhD
- University of California, San Diego (1983)
- BS
- Massachusetts Institute of Technology, Biology (1976)
Research
Overview
1. The receptor tyrosine kinase ErbB2/HER2 drives 25% of breast cancers. This receptor is the target for two drugs in use for breast cancer treatment, Herceptin/Trastuzumab and Tykerb/Lapatinib. In order to understand why this receptor is so important in human cancer, and to improve therapeutic targeting of ErbB2/HER2, we investigate normal and pathological functions of this receptor in mammary tissue. Our work spans from fundamental studies on signal transduction to analysis of ERBB2 in human cancer. ERBB2 works in close partnership with other members of the EGF receptor (ERBB family) of tyrosine kinases, so we also study differential signaling by the three related receptors (EGF receptor [HER]), ERBB3 [HER3], ErbB4[HER4).
2. The growing availability of cancer drugs that target receptors and other signaling proteins has created a need to develop integrated methods for best matching of patients to the appropriate target drugs. We are investigating use of DNA-based and functional approaches for predicting response to targeted therapies, in breast cancer, lung cancer, pancreatic cancer, and melanoma.
Medical Subject Headings (MeSH)
ORCID
0000-0003-4018-5348- View Lab Website
Stern Lab
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
David Rimm, MD, PhD
Goran Micevic, MD, PhD
Zhaoxia Sun, PhD
Gary Bellinger
Lakshmi Bangalore, PhD
Michael DiGiovanna, MD, PhD
Signal Transduction
DNA Damage
Breast Neoplasms
Melanoma
Neoplasms
Publications
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 ResearchAltmetricConceptsBreast 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsMutant 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH 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 ResearchCitationsMeSH Keywords and ConceptsConceptsKinase 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPhosphorylation 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH 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 ResearchCitationsMeSH KeywordsBinding 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 ResearchCitationsAltmetricMeSH Keywords3T3 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 Alignment
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Brady Memorial Laboratory
310 Cedar Street, Ste BML 348A
New Haven, CT 06510
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203.785.2443Appointments
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