Anna Arnal Estape, PhD, BS
Associate Research ScientistCards
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Contact Info
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
Veronica Chiang, MD, FAANS
Abhijit Patel, MD, PhD
Francesc Lopez-Giraldez, PhD
Harriet Kluger, MD
Katerina Politi, PhD
Neoplasm Metastasis
Tumor Microenvironment
Disease Models, Animal
Adenocarcinoma
Publications
2024
BSLM-10 MOLECULAR AND HISTOLOGICAL CHARACTERIZATION OF NSCLC PROGRESSION TO LEPTOMENINGEAL METASTASIS WITH COMORBID INTRAPARENCHYMAL DISEASE
Kandigian S, Chande S, Dolezal D, Tang T, Wang D, Arnal-Estapé A, Cheok S, McGuone D, Liu Y, Goldberg S, Blondin N, Chiang V, Nguyen D. BSLM-10 MOLECULAR AND HISTOLOGICAL CHARACTERIZATION OF NSCLC PROGRESSION TO LEPTOMENINGEAL METASTASIS WITH COMORBID INTRAPARENCHYMAL DISEASE. Neuro-Oncology Advances 2024, 6: i7-i7. PMCID: PMC11296776, DOI: 10.1093/noajnl/vdae090.020.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerLeptomeningeal diseaseCentral nervous systemLeptomeningeal metastasesParenchymal metastasesCerebrospinal fluidTumor cellsTyrosine kinase inhibitor treatmentCell lung cancerKinase inhibitor treatmentCerebrospinal fluid of patientsCell linesCerebral lateral ventriclesIntra-arterial injectionTGF-b signalingIn vivo passageIntraparenchymal diseaseMechanisms of progressionTumor microenvironmentMultiplex immunofluorescenceAggressive treatmentLeptomeningeal infiltrationPerivascular invasionIntraparenchymal metastasesMurine model154 Elucidating the Immune Landscape of Radiation Necrosis Through Single Cell Analysis of Recurrent Brain Lesions in Patients After Stereotactic Radio Surgery
Robert S, Kiziltug E, Lu B, Arnal-Estape A, Nguyen D, Chiang V. 154 Elucidating the Immune Landscape of Radiation Necrosis Through Single Cell Analysis of Recurrent Brain Lesions in Patients After Stereotactic Radio Surgery. Neurosurgery 2024, 70: 35-36. DOI: 10.1227/neu.0000000000002809_154.Peer-Reviewed Original ResearchConceptsRadiation necrosisFluorescence-activated cell sortingInterferon-stimulated genesStereotactic radiosurgeryNatural killerMyeloid cellsImmune cellsRadiosurgical treatment of brain metastasesTreatment of brain metastasesCD4+ T cellsExpression of immune cellsMorbid side effectsTreatment of RNSubpopulations of myeloid cellsStereotactic radio surgeryMetastatic brain tumorsInvasive brain biopsyCellular immune profilesInflammatory immune responseCSF of patientsRN patientsBrain metastasesCD8+Immunotherapy optionsMetastatic tumorsASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts.
Hu B, Wiesehöfer M, de Miguel F, Liu Z, Chan L, Choi J, Melnick M, Arnal Estape A, Walther Z, Zhao D, Lopez-Giraldez F, Wurtz A, Cai G, Fan R, Gettinger S, Xiao A, Yan Q, Homer R, Nguyen D, Politi K. ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts. Cancer Research 2024, 84: 1303-1319. PMID: 38359163, PMCID: PMC11142404, DOI: 10.1158/0008-5472.can-23-0438.Peer-Reviewed Original ResearchCitationsAltmetricConceptsTyrosine kinase inhibitorsPatient-derived xenograftsEGFR mutant lung cancerMutant lung cancerPre-treatment tumorsResidual diseaseDrug toleranceLung cancerResidual tumor cells in vivoEGFR mutant lung adenocarcinomaTyrosine kinase inhibitor osimertinibEGFR tyrosine kinase inhibitorsTyrosine kinase inhibitor treatmentTumor cells in vivoMutant lung adenocarcinomaMaximal tumor regressionTranscription factor Ascl1Drug-tolerant cellsTime of maximal responseEvidence of cellsCells in vivoOsimertinib treatmentTumor regressionSingle cell transcriptional profilingTumor cells
2023
BSBM-18 SINGLE-CELL PROFILING TUMOR-INFILTRATING IMMUNE CELLS REVEALS CXCL13+ FOLLICULAR HELPER-LIKE CD4+ T CELLS IN HUMAN BRAIN TUMORS
Lu B, Lucca L, DiStasio M, Liu Y, Pham G, Buitrago-Pocasangre N, Arnal-Estape A, Moliterno J, Chiang V, Omuro A, Hafler D. BSBM-18 SINGLE-CELL PROFILING TUMOR-INFILTRATING IMMUNE CELLS REVEALS CXCL13+ FOLLICULAR HELPER-LIKE CD4+ T CELLS IN HUMAN BRAIN TUMORS. Neuro-Oncology Advances 2023, 5: iii4-iii4. PMCID: PMC10402449, DOI: 10.1093/noajnl/vdad070.014.Peer-Reviewed Original ResearchConceptsT cell populationsT cell functionT cellsHigh-grade gliomasBrain metastasesHuman brain tumorsImmune cellsBrain tumorsNon-small cell lung cancer brain metastasesB cellsAnti-PD-1 therapy responseCell lung cancer brain metastasesLung cancer brain metastasesProductive antitumor immune responsesFollicular helper T cellsT-cell receptor sequencingTumor-infiltrating T cellsAntitumor T-cell functionCancer brain metastasesCo-inhibitory receptorsAntitumor immune responseCell receptor sequencingLonger overall survivalCell functionTertiary lymphoid structures465 Defining the Immune Profile of Radiation Necrosis Through Single-cell Analysis of Intracranial Lesions
Robert S, Lu B, Arnal-Estape A, Nguyen D, Chiang V. 465 Defining the Immune Profile of Radiation Necrosis Through Single-cell Analysis of Intracranial Lesions. Neurosurgery 2023, 69: 97-98. DOI: 10.1227/neu.0000000000002375_465.Peer-Reviewed Original ResearchConceptsRadiation necrosisFluorescence-activated cell sortingImmune profileNatural killer (NK) cellsIncidence of radiation necrosisManagement of brain metastasesMetastatic brain tumor patientsMorbid side effectsTreatment of RNRecurrent metastatic diseaseExpression of Foxp3Cytotoxic T cellsInvasive brain biopsyCellular immune profilesInterleukin-7 receptorBrain tumor patientsBrain metastasesMetastatic diseaseMetastatic tumorsImmune landscapeIntraoperative samplesPatient survivalT cellsBrain biopsyIntracranial lesions
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 suppression513 Surveilling Cerebrospinal Fluid Protein Biomarkers in Brain Metastasis
Cheok S, Arnal-Estape A, Wei W, Nguyen D, Chiang V. 513 Surveilling Cerebrospinal Fluid Protein Biomarkers in Brain Metastasis. Neurosurgery 2022, 68: 129-129. DOI: 10.1227/neu.0000000000001880_513.Peer-Reviewed Original ResearchConceptsBrain metastasesCerebrospinal fluidIntraparenchymal diseaseCentral nervous system pathologyCerebrospinal fluid (CSF) protein biomarkersIntraparenchymal brain metastasesManagement of patientsNormal pressure hydrocephalusNervous system pathologyCurrent diagnostic standardNon-malignant samplesWarrants further explorationCSF profilePressure hydrocephalusRadiation necrosisLung cancerSimilar pathogenesisBrain parenchymaInflammatory diseasesIntracranial diseaseBreast cancerClinical dataCSF leakTreatment responsePatients
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
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