Anna Arnal Estape, PhD, BS
Associate Research ScientistCards
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About
Titles
Associate Research Scientist
Appointments
Medical Oncology
Associate Research ScientistPrimary
Other Departments & Organizations
Education & Training
- Associate Research Scientist
- Yale University (2022)
- Postdoctoral Associate
- Yale University (2018)
- Postdoctoral Associate
- Albert Einstein School of Medicine (2014)
- PhD
- Universitat de Barcelona, Biomedicine (2011)
- BS
- Universitat Pompeu Fabra, Biology (2006)
Research
Overview
Cancer cells disobey signaling networks that control cell division and differentiation during tumor progression and metastasis. My early work during my PhD focused on the role of a breast cancer oncogenic signal, ERBB2, in the evasion of two tumor suppressor mechanisms in breast cancer cells, namely TGFb cytostasis and oncogene-induced senescence. We identified C/EBPb as the molecular link between ERBB2 oncogenic signal and the evasion of these two potent suppressive functions in tumor cells. Despite improvement in primary tumor targeted, metastasis accounts for 90% of solid tumors-related death. We performed an in vivo screen that identified mediators of bone metastasis in breast cancer cells. We validated Noggin and Maf as key effectors of bone metastasis. These publications report the need for stratification of breast cancer patients to determine those with increased risk of bone relapse that will benefit from the therapeutic targeting of these pathways.
In my postdoctoral training at Albert Einstein, I acquired expertise in genetically engineered mouse models (GEMMs) of prostate cancer and microenvironmental cues that promotes tumor progression and metastasis such as angiogenesis and the autonomous nervous system. We identified that adrenergic signaling is responsible for a metabolic switch on endothelial cells that allow prostate progression from PIN stage to adenocarcinoma.
In 2014 I joined the laboratory of Don Nguyen in the Pathology department to continue my studies of tumor biology and metastasis of non-small cell lung cancers (NSCLCs). We are interested in determining the function of a transcriptional network, which normally controls epithelial differentiation in the airways, in different NSCLC subtypes. We found that this transcriptional network correlates with poor outcome in patients with lung adenocarcinoma (LUAD), a distinct subtype of NSCLC. To this end, we have developed several GEMMs of LUAD to interrogate the requirements of the metastasis suppressors Hopx and Gata6 in tumor initiation.
I believe science requires a collaborative environment for success. During my PhD and postdoctoral training, I developed my research in tight collaboration with different coworkers within the laboratory as well as researchers from different institutions. From these fruitful collaborations, several projects were published in high impact journals within our field.
Medical Subject Headings (MeSH)
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Don Nguyen, PhD, BSc
Veronica Chiang, MD, FAANS
Francesc Lopez-Giraldez, PhD
Harriet Kluger, MD
Abhijit Patel, MD, PhD
Amer Balabaki
Tumor Microenvironment
Disease Models, Animal
Adenocarcinoma
Neoplasm Metastasis
Publications
2022
Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer
Adua S, Arnal-Estapé A, Zhao M, Qi B, Liu Z, Kravitz C, Hulme H, Strittmatter N, López-Giráldez F, Chande S, Albert A, Melnick M, Hu B, Politi K, Chiang V, Colclough N, Goodwin R, Cross D, Smith P, Nguyen D. Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer. Nature Communications 2022, 13: 7690. PMID: 36509758, PMCID: PMC9744876, DOI: 10.1038/s41467-022-34889-z.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsGene expression programsRas homolog family member ACancer cellsFamily member AEpidermal growth factor receptorExpression programsMetastatic cancer cellsSRF signalingGrowth factor receptorTumor microenvironmentLung cancerFunctional linkExtracellular lamininDrug-resistant cancer cellsMutant non-small cell lung cancerNon-small cell lung cancerCentral nervous system relapseMolecular studiesMember AEGFR-mutant lung cancerFactor receptorNervous system relapseCell lung cancerDisseminated tumor cellsBrain tumor microenvironmentHuman WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation
Cai WL, Chen JF, Chen H, Wingrove E, Kurley SJ, Chan LH, Zhang M, Arnal-Estape A, Zhao M, Balabaki A, Li W, Yu X, Krop ED, Dou Y, Liu Y, Jin J, Westbrook TF, Nguyen DX, Yan Q. Human WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation. ELife 2022, 11: e78163. PMID: 36043466, PMCID: PMC9584608, DOI: 10.7554/elife.78163.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsBreast cancer cellsMetastatic breast cancerBreast cancerRibosomal gene expressionCancer cellsKnockdown of WDR5Vivo genetic screenReversible epigenetic mechanismsGenetic screenTranslation regulationTriple-negative breast cancerEpigenetic regulatorsEpigenetic mechanismsBreast cancer growthCancer-related deathTranslation efficiencyWDR5Novel therapeutic strategiesTranslation rateGene expressionCell growthAdvanced diseaseEffective therapyMetastatic capabilityPotent suppression
2021
Preclinical Models for the Study of Lung Cancer Pathogenesis and Therapy Development
Arnal-Estapé A, Foggetti G, Starrett JH, Nguyen DX, Politi K. Preclinical Models for the Study of Lung Cancer Pathogenesis and Therapy Development. Cold Spring Harbor Perspectives In Medicine 2021, 11: a037820. PMID: 34518338, PMCID: PMC8634791, DOI: 10.1101/cshperspect.a037820.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCitationsAltmetricMeSH Keywords and ConceptsConceptsPatient-derived xenograftsPreclinical modelsLung cancer translational researchExperimental preclinical modelsLung cancer pathogenesisLung cancer cell linesNumerous preclinical modelsLung cancer subtypesLung cancer researchCancer translational researchCancer cell linesMouse modelNew therapeutic vulnerabilitiesCancer subtypesTumor progressionCancer pathogenesisTherapeutic vulnerabilitiesTranslational researchTherapy developmentCell linesCancer researchThree-dimensional culture systemCulture systemPathogenesisXenograftsTumor DNA Mutations From Intraparenchymal Brain Metastases Are Detectable in CSF
Cheok SK, Narayan A, Arnal-Estape A, Gettinger S, Goldberg SB, Kluger HM, Nguyen D, Patel A, Chiang V. Tumor DNA Mutations From Intraparenchymal Brain Metastases Are Detectable in CSF. JCO Precision Oncology 2021, 5: 163-172. PMID: 34250381, PMCID: PMC8232069, DOI: 10.1200/po.20.00292.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsIntraparenchymal brain metastasesBrain metastasesCell-free DNAExtracranial tumorsBrain metastasis tissuesProgressive brain metastasesThird of patientsNormal pressure hydrocephalusTumor DNA mutationsPrimary cancer typeAnalysis of CSFSamples of CSFLeptomeningeal diseaseEffective surrogate markerBrain biopsyPressure hydrocephalusLumbar punctureSurrogate markerCancer-associated genesMetastasis tissuesPatientsMetastasisDiscordant responsesRenal cellsGenomic profiling
2020
Tumor progression and chromatin landscape of lung cancer are regulated by the lineage factor GATA6
Arnal-Estapé A, Cai WL, Albert AE, Zhao M, Stevens LE, López-Giráldez F, Patel KD, Tyagi S, Schmitt EM, Westbrook TF, Nguyen DX. Tumor progression and chromatin landscape of lung cancer are regulated by the lineage factor GATA6. Oncogene 2020, 39: 3726-3737. PMID: 32157212, PMCID: PMC7190573, DOI: 10.1038/s41388-020-1246-z.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsChromatin landscapeTranscription factorsBone morphogenetic protein (BMP) signalingDiverse transcriptional programsAlters chromatin accessibilityMultiple genomic lociMorphogenetic protein signalingDistal enhancer elementsSelective transcription factorsEpithelial cell typesSurfactant protein CChromatin accessibilityGenomic lociTranscriptional programsLung adenocarcinoma progressionTumor progressionEpigenetic mechanismsProtein signalingBiological functionsLUAD progressionLUAD cellsEnhancer elementsLineage dependencyTumor suppressionLung cancer cellsSpecific chromatin landscapes and transcription factors couple breast cancer subtype with metastatic relapse to lung or brain
Cai WL, Greer CB, Chen JF, Arnal-Estapé A, Cao J, Yan Q, Nguyen DX. Specific chromatin landscapes and transcription factors couple breast cancer subtype with metastatic relapse to lung or brain. BMC Medical Genomics 2020, 13: 33. PMID: 32143622, PMCID: PMC7060551, DOI: 10.1186/s12920-020-0695-0.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsOpen chromatin signaturesTranscription factorsChromatin landscapeChromosome conformation captureOpen chromatin landscapeSpecific chromatin landscapesHomophilic cell adhesionTransposase-accessible chromatinEnhancer-promoter interactionsSpecific transcription factorsActive chromatin sitesATAC-seq dataMetastatic cellsGene expression dataChromatin signaturesConformation captureChromatin sitesActive chromatinATAC-seqEpigenomic propertiesChIP-seqChromatin immunoprecipitationEndothelial cell migrationEpigenomic analysisTranscriptomic differences
2019
Nestin+NG2+ Cells Form a Reserve Stem Cell Population in the Mouse Prostate
Hanoun M, Arnal-Estapé A, Maryanovich M, Zahalka AH, Bergren SK, Chua CW, Leftin A, Brodin PN, Shen MM, Guha C, Frenette PS. Nestin+NG2+ Cells Form a Reserve Stem Cell Population in the Mouse Prostate. Stem Cell Reports 2019, 12: 1201-1211. PMID: 31130357, PMCID: PMC6565923, DOI: 10.1016/j.stemcr.2019.04.019.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsReserve stem cell populationLineage-tracing analysisStem cell populationStem cell activityProstate stem cellsEpithelial cellsBipotential capacityProstate epithelial cellsTissue maintenanceLuminal epithelial cellsMesenchymal cellsStem cellsCell populationsOrgan damageProstate organoidsNG2 expressionRegenerative capacityRare subsetMouse prostateProstate epitheliumTransgenic miceTissue graftCell activityClonal levelCellsTranscriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis
Wingrove E, Liu ZZ, Patel KD, Arnal-Estapé A, Cai WL, Melnick MA, Politi K, Monteiro C, Zhu L, Valiente M, Kluger HM, Chiang VL, Nguyen DX. Transcriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis. Cell Reports 2019, 27: 1277-1292.e7. PMID: 31018140, PMCID: PMC6592283, DOI: 10.1016/j.celrep.2019.03.085.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsBrain metastasesBrain tumor microenvironmentLineage programTumor microenvironmentTumor plasticityStromal gene expressionTranscriptomic hallmarksGene expressionTranscriptional hallmarksMultiple tumor typesMolecular landscapeStromal interactionsMajor siteIntact tissueNeuroinflammatory responseSyngeneic modelPatient biopsiesTumor typesMetastasisMalignant cellsDifferent subtypesTumor cellsHallmarkTranscriptomeCells
2018
Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment.
Stevens LE, Arnal-Estapé A, Nguyen DX. Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment. Journal Of Visualized Experiments 2018 PMID: 30010648, PMCID: PMC6102009, DOI: 10.3791/56650.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsCancer cell engraftmentAirways of miceLung cancer cellsCell engraftmentLung cancerTumor cellsTumorigenic capacityNew orthotopic modelNon-physiological sitesTumor cell injectionCancer cellsLung tumor incidenceTreatment-refractory diseaseFull clinical spectrumLung cancer subtypesLung adenocarcinoma subtypesAdditional animal modelsStrains of miceFlanks of miceRefractory diseaseThoracic malignanciesAdenocarcinoma subtypeClinical spectrumOrthotopic transplantationTumor incidenceMSK1 regulates luminal cell differentiation and metastatic dormancy in ER+ breast cancer.
Gawrzak S, Rinaldi L, Gregorio S, Arenas EJ, Salvador F, Urosevic J, Figueras-Puig C, Rojo F, Del Barco Barrantes I, Cejalvo JM, Palafox M, Guiu M, Berenguer-Llergo A, Symeonidi A, Bellmunt A, Kalafatovic D, Arnal-Estapé A, Fernández E, Müllauer B, Groeneveld R, Slobodnyuk K, Stephan-Otto Attolini C, Saura C, Arribas J, Cortes J, Rovira A, Muñoz M, Lluch A, Serra V, Albanell J, Prat A, Nebreda AR, Benitah SA, Gomis RR. MSK1 regulates luminal cell differentiation and metastatic dormancy in ER+ breast cancer. Nature Cell Biology 2018, 20: 211-221. PMID: 29358704, DOI: 10.1038/s41556-017-0021-z.Peer-Reviewed Original Research
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