2020
Longitudinal analyses reveal immunological misfiring in severe COVID-19
Lucas C, Wong P, Klein J, Castro TBR, Silva J, Sundaram M, Ellingson MK, Mao T, Oh JE, Israelow B, Takahashi T, Tokuyama M, Lu P, Venkataraman A, Park A, Mohanty S, Wang H, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Muenker MC, Fournier JB, Campbell M, Odio CD, Casanovas-Massana A, Herbst R, Shaw A, Medzhitov R, Schulz W, Grubaugh N, Dela Cruz C, Farhadian S, Ko A, Omer S, Iwasaki A. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 2020, 584: 463-469. PMID: 32717743, PMCID: PMC7477538, DOI: 10.1038/s41586-020-2588-y.Peer-Reviewed Original ResearchConceptsSevere COVID-19Moderate COVID-19Immune signaturesDisease outcomeCOVID-19Disease trajectoriesInterleukin-5Early immune signaturesInnate cell lineagesType 2 effectorsT cell numbersPoor clinical outcomeWorse disease outcomesImmune response profileCoronavirus disease 2019Distinct disease trajectoriesCytokine levelsImmunological correlatesImmune profileClinical outcomesEarly elevationImmune profilingIL-13Immunoglobulin EDisease 2019
2015
Co-occurring Genomic Alterations Define Major Subsets of KRAS-Mutant Lung Adenocarcinoma with Distinct Biology, Immune Profiles, and Therapeutic Vulnerabilities
Skoulidis F, Byers LA, Diao L, Papadimitrakopoulou VA, Tong P, Izzo J, Behrens C, Kadara H, Parra ER, Canales JR, Zhang J, Giri U, Gudikote J, Cortez MA, Yang C, Fan Y, Peyton M, Girard L, Coombes KR, Toniatti C, Heffernan TP, Choi M, Frampton GM, Miller V, Weinstein JN, Herbst RS, Wong KK, Zhang J, Sharma P, Mills GB, Hong WK, Minna JD, Allison JP, Futreal A, Wang J, Wistuba II, Heymach JV. Co-occurring Genomic Alterations Define Major Subsets of KRAS-Mutant Lung Adenocarcinoma with Distinct Biology, Immune Profiles, and Therapeutic Vulnerabilities. Cancer Discovery 2015, 5: 860-877. PMID: 26069186, PMCID: PMC4527963, DOI: 10.1158/2159-8290.cd-14-1236.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesCell Line, TumorCluster AnalysisDNA-Binding ProteinsGene ExpressionGene Expression ProfilingGenetic VariationGenomicsHumansInflammationLung NeoplasmsMutationOxidative StressPrognosisProtein Serine-Threonine KinasesRas ProteinsSignal TransductionTranscription FactorsTumor Suppressor ProteinsConceptsKRAS-mutant lung adenocarcinomaCo-occurring genomic alterationsLung adenocarcinomaDistinct biologyTherapeutic vulnerabilitiesSTK11/LKB1Hsp90 inhibitor therapyRelapse-free survivalDrug sensitivity patternsGenomic alterationsCDKN2A/BKC tumorsInflammatory markersMucinous histologyImmune markersImmune profilePD-L1AdenocarcinomaSensitivity patternMajor subsetNKX2-1 transcription factorLow expressionTumorsGenetic alterationsEffector molecules
2013
An Epithelial–Mesenchymal Transition Gene Signature Predicts Resistance to EGFR and PI3K Inhibitors and Identifies Axl as a Therapeutic Target for Overcoming EGFR Inhibitor Resistance
Byers LA, Diao L, Wang J, Saintigny P, Girard L, Peyton M, Shen L, Fan Y, Giri U, Tumula PK, Nilsson MB, Gudikote J, Tran H, Cardnell RJ, Bearss DJ, Warner SL, Foulks JM, Kanner SB, Gandhi V, Krett N, Rosen ST, Kim ES, Herbst RS, Blumenschein GR, Lee JJ, Lippman SM, Ang KK, Mills GB, Hong WK, Weinstein JN, Wistuba II, Coombes KR, Minna JD, Heymach JV. An Epithelial–Mesenchymal Transition Gene Signature Predicts Resistance to EGFR and PI3K Inhibitors and Identifies Axl as a Therapeutic Target for Overcoming EGFR Inhibitor Resistance. Clinical Cancer Research 2013, 19: 279-290. PMID: 23091115, PMCID: PMC3567921, DOI: 10.1158/1078-0432.ccr-12-1558.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxl Receptor Tyrosine KinaseCarcinoma, Non-Small-Cell LungCell Line, TumorCluster AnalysisDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionErbB ReceptorsGene Expression ProfilingHumansLung NeoplasmsMiceNeoplasm MetastasisPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProteomeProteomicsProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesRecurrenceReproducibility of ResultsConceptsEpithelial-mesenchymal transitionPotential therapeutic targetEGFR inhibitor resistanceTherapeutic targetEMT signatureInhibitor resistanceMesenchymal transition gene signatureMesenchymal cellsCell linesBiomarker-Integrated ApproachesPI3K/Akt pathway inhibitorNon-small cell lung carcinoma cell lineEGFR mutation statusReceptor tyrosine kinase AXLNSCLC cell linesPI3K/Akt inhibitorCell lung carcinoma cell lineGene expression profilesTyrosine kinase AXLLung carcinoma cell linePI3K inhibitorsDrug response analysisAkt pathway inhibitorCarcinoma cell linesErlotinib resistance