2019
The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma
Truini A, Starrett JH, Stewart T, Ashtekar K, Walther Z, Wurtz A, Lu D, Park JH, DeVeaux M, Song X, Gettinger S, Zelterman D, Lemmon MA, Goldberg SB, Politi K. The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma. Clinical Cancer Research 2019, 25: 6382-6391. PMID: 31182434, PMCID: PMC6825535, DOI: 10.1158/1078-0432.ccr-19-0780.Peer-Reviewed Original Research
2014
Acquired Resistance of EGFR-Mutant Lung Adenocarcinomas to Afatinib plus Cetuximab Is Associated with Activation of mTORC1
Pirazzoli V, Nebhan C, Song X, Wurtz A, Walther Z, Cai G, Zhao Z, Jia P, de Stanchina E, Shapiro EM, Gale M, Yin R, Horn L, Carbone DP, Stephens PJ, Miller V, Gettinger S, Pao W, Politi K. Acquired Resistance of EGFR-Mutant Lung Adenocarcinomas to Afatinib plus Cetuximab Is Associated with Activation of mTORC1. Cell Reports 2014, 7: 999-1008. PMID: 24813888, PMCID: PMC4074596, DOI: 10.1016/j.celrep.2014.04.014.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAfatinibAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorCetuximabDrug Resistance, NeoplasmErbB ReceptorsHumansLung NeoplasmsMechanistic Target of Rapamycin Complex 1MiceMice, NudeMice, TransgenicMultiprotein ComplexesMutationQuinazolinesRandom AllocationTOR Serine-Threonine KinasesXenograft Model Antitumor AssaysConceptsTyrosine kinase inhibitorsFirst-generation tyrosine kinase inhibitorEGFR-mutant lung adenocarcinomaLung adenocarcinomaMechanisms of resistanceEGFR antibody cetuximabPotential therapeutic strategyBiopsy specimensAntibody cetuximabDrug combinationsMouse modelTherapeutic strategiesAfatinibAddition of rapamycinCetuximabDual inhibitionAcquired ResistanceKinase inhibitorsGenomic alterationsAdenocarcinomaPatientsActivationGenomic mechanismsDrugsMTORC1 activationReduced NF1 Expression Confers Resistance to EGFR Inhibition in Lung Cancer
de Bruin EC, Cowell C, Warne PH, Jiang M, Saunders RE, Melnick MA, Gettinger S, Walther Z, Wurtz A, Heynen GJ, Heideman DA, Gómez-Román J, García-Castaño A, Gong Y, Ladanyi M, Varmus H, Bernards R, Smit EF, Politi K, Downward J. Reduced NF1 Expression Confers Resistance to EGFR Inhibition in Lung Cancer. Cancer Discovery 2014, 4: 606-619. PMID: 24535670, PMCID: PMC4011693, DOI: 10.1158/2159-8290.cd-13-0741.Peer-Reviewed Original ResearchConceptsLung cancerMAP-ERK kinase (MEK) inhibitorsEGF receptorEGFR-mutant lung adenocarcinomaKinase inhibitorsHuman lung cancer cell linesResistance of lungSubgroup of patientsLung cancer cell linesCancer cell linesClinical responsivenessCombination therapyEGFR-TKIEGFR mutationsErlotinib resistanceLung adenocarcinomaRAS-ERK signalingEGFR inhibitionMEK inhibitorsErlotinibReduced expressionNF1 expressionPatientsCell linesNeurofibromin levels
2012
MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice
Hoshi N, Schenten D, Nish SA, Walther Z, Gagliani N, Flavell RA, Reizis B, Shen Z, Fox JG, Iwasaki A, Medzhitov R. MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice. Nature Communications 2012, 3: 1120. PMID: 23047678, PMCID: PMC3521499, DOI: 10.1038/ncomms2113.Peer-Reviewed Original ResearchConceptsToll-like receptorsInterleukin-10Mononuclear phagocytesIL-10-deficient miceT helper 17 responsesColonic mononuclear phagocytesDevelopment of colitisInflammatory bowel diseaseColitis developmentBowel diseaseInterleukin-23MyD88 expressionInterleukin-1βInterleukin-6Intestinal homeostasisEpithelial expressionMyD88Multiple cell typesMiceCell typesReceptorsPhagocytesBacterial sensingDistinct populationsHigh levels
2011
Mitochondrial Genome Instability and ROS Enhance Intestinal Tumorigenesis in APCMin/+ Mice
Woo DK, Green PD, Santos JH, D'Souza AD, Walther Z, Martin WD, Christian BE, Chandel NS, Shadel GS. Mitochondrial Genome Instability and ROS Enhance Intestinal Tumorigenesis in APCMin/+ Mice. American Journal Of Pathology 2011, 180: 24-31. PMID: 22056359, PMCID: PMC3338350, DOI: 10.1016/j.ajpath.2011.10.003.Peer-Reviewed Original ResearchConceptsMitochondrial genome instabilityGenome instabilityMtDNA instabilityMaintenance of mtDNAMitochondrial transcription factor AMitochondrial dysfunctionIntestinal tumorigenesisTranscription factor AWnt/β-catenin signalingMitochondrial oxidative phosphorylationMitochondrial ROS productionΒ-catenin signalingOxidative mtDNA damageReactive oxygen species productionMitochondrial DNAOxygen species productionMouse cellsOxidative phosphorylationOvert phenotypeMitochondrial ROSMtDNA damageMtDNA depletionCancer phenotypeAltered amountsTumorigenesis
2009
CASK Deletion in Intestinal Epithelia Causes Mislocalization of LIN7C and the DLG1/Scrib Polarity Complex without Affecting Cell Polarity
Lozovatsky L, Abayasekara N, Piawah S, Walther Z. CASK Deletion in Intestinal Epithelia Causes Mislocalization of LIN7C and the DLG1/Scrib Polarity Complex without Affecting Cell Polarity. Molecular Biology Of The Cell 2009, 20: 4489-4499. PMID: 19726564, PMCID: PMC2770937, DOI: 10.1091/mbc.e09-04-0280.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorEpithelial polarityNormal localizationBasolateral membranePolarity complexMammalian orthologsCell polarityCaenorhabditis elegansMAGUK familyProtein complexesIntestinal epitheliumGrowth factor receptorLIN7CBasolateral localizationComplete knockoutCASK expressionTumor suppressorSubcellular distributionDlg1CASK deletionFactor receptorImmunofluorescence analysisErbB-2Intestinal homeostasisAppropriate localizationIsospora cholangiopathy: case study with histologic characterization and molecular confirmation
Walther Z, Topazian MD. Isospora cholangiopathy: case study with histologic characterization and molecular confirmation. Human Pathology 2009, 40: 1342-1346. PMID: 19447468, DOI: 10.1016/j.humpath.2009.01.020.Peer-Reviewed Case Reports and Technical NotesMeSH KeywordsAcquired Immunodeficiency SyndromeAdultAnimalsAnti-Infective AgentsAntiparasitic AgentsBile Ducts, ExtrahepaticBile Ducts, IntrahepaticBiopsyCholangiopancreatography, Endoscopic RetrogradeCholangitis, SclerosingHumansIsosporaIsosporiasisIvermectinMalePolymerase Chain ReactionTreatment OutcomeTrimethoprim, Sulfamethoxazole Drug CombinationConceptsAIDS patientsBile ductIsospora belliCommon bile duct biopsiesPolymerase chain reaction-based molecular analysisBile duct biopsyPrimary sclerosing cholangitisExtrahepatic bile ductRare opportunistic pathogenEndoscopic retrograde cholangiopancreatographyIntracellular protozoan parasiteDuct biopsySclerosing cholangitisUncommon causeAcute illnessHIV statusRadiologic findingsRetrograde cholangiopancreatographyTravelers' diarrheaWest African menHepatobiliary diseaseHistologic characterizationSmall intestineDiarrheaIsosporiasis
2008
A PDZ‐Binding Motif Controls Basolateral Targeting of Syndecan‐1 Along the Biosynthetic Pathway in Polarized Epithelial Cells
Maday S, Anderson E, Chang HC, Shorter J, Satoh A, Sfakianos J, Fölsch H, Anderson JM, Walther Z, Mellman I. A PDZ‐Binding Motif Controls Basolateral Targeting of Syndecan‐1 Along the Biosynthetic Pathway in Polarized Epithelial Cells. Traffic 2008, 9: 1915-1924. PMID: 18764819, PMCID: PMC2820280, DOI: 10.1111/j.1600-0854.2008.00805.x.Peer-Reviewed Original ResearchConceptsPolarized epithelial cellsBiosynthetic pathwayPDZ domain-containing proteinsType II PDZDomain-containing proteinsPDZ-Binding MotifSyndecan-1Cell surface proteoglycansEpithelial cellsBasolateral targetingNormal epithelial morphologyBasolateral domainMotif leadPlasma membranePDZBasolateral localizationSurface proteoglycansBasolateral surfaceApical surfaceEpithelial morphologyMotifPotential rolePathwayCellsMislocalization
2006
The Unique-5 and -6 Motifs of ZO-1 Regulate Tight Junction Strand Localization and Scaffolding Properties
Fanning AS, Little BP, Rahner C, Utepbergenov D, Walther Z, Anderson JM. The Unique-5 and -6 Motifs of ZO-1 Regulate Tight Junction Strand Localization and Scaffolding Properties. Molecular Biology Of The Cell 2006, 18: 721-731. PMID: 17182847, PMCID: PMC1805089, DOI: 10.1091/mbc.e06-08-0764.Peer-Reviewed Original ResearchConceptsProper cellular locationMAGUK protein familyZO-1Tight junction transmembrane proteinsGUK domainTight junctionsMAGUK proteinsProtein familyScaffolding functionsTransmembrane proteinComplex protein bindingCellular locationLateral cell membranesRegulatory functionsC-terminalCultured cellsCell membraneJunction strandsVariable regionsMotifProteinBindingU5Protein bindingMAGUKs
1998
Human CASK/LIN-2 Binds Syndecan-2 and Protein 4.1 and Localizes to the Basolateral Membrane of Epithelial Cells
Cohen A, Wood D, Marfatia S, Walther Z, Chishti A, Anderson J. Human CASK/LIN-2 Binds Syndecan-2 and Protein 4.1 and Localizes to the Basolateral Membrane of Epithelial Cells. Journal Of Cell Biology 1998, 142: 129-138. PMID: 9660868, PMCID: PMC2133028, DOI: 10.1083/jcb.142.1.129.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium-Calmodulin-Dependent Protein KinasesCarrier ProteinsCloning, MolecularCytoskeletal ProteinsEpithelial CellsGuanylate KinasesHelminth ProteinsHumansMembrane GlycoproteinsMembrane ProteinsMicrofilament ProteinsNeuropeptidesNucleoside-Phosphate KinaseProteoglycansRabbitsRatsRecombinant Fusion ProteinsSpectrinSyndecan-2ConceptsProtein 4.1LIN-2Membrane domainsRas/MAP kinase pathwayMembrane-associated guanylate kinase (MAGUK) familySyndecan-2Membrane-associated guanylate kinaseVulval precursor cellsTwo-hybrid screenBasal plasma membrane domainsPlasma membrane domainsExtracellular matrixCASK/LINHeparan sulfate proteoglycan syndecan-2Basal membrane domainsMAP kinase pathwayProteoglycan syndecan-2Receptor tyrosine kinasesDifferent epithelial cell typesEpithelial cell typesLET-23Caenorhabditis elegansPDZ domainActin cytoskeletonGuanylate kinase
1996
The kinesin-homologous protein encoded by the Chlamydomonas FLA10 gene is associated with basal bodies and centrioles
Vashishtha M, Walther Z, Hall J. The kinesin-homologous protein encoded by the Chlamydomonas FLA10 gene is associated with basal bodies and centrioles. Journal Of Cell Science 1996, 109: 541-549. PMID: 8907700, DOI: 10.1242/jcs.109.3.541.Peer-Reviewed Original ResearchConceptsBasal bodiesMitotic spindleHomologous proteinsCell cycleUni linkage groupFamily of proteinsMotor domainCarboxy-terminal thirdTemperature-sensitive defectKinesin-related proteinEukaryotic evolutionFlagellar assemblyFlagellar developmentLinkage groupsFlagellar componentsSubcellular localizationPunctate structuresSea urchinsMolecular defectsProteinCentriolesAnalogous roleDirect roleMitosisGenes
1995
The uni chromosome of Chlamydomonas: histone genes and nucleosome structure
Walther Z, Hall J. The uni chromosome of Chlamydomonas: histone genes and nucleosome structure. Nucleic Acids Research 1995, 23: 3756-3763. PMID: 7479007, PMCID: PMC307276, DOI: 10.1093/nar/23.18.3756.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceCell DivisionChlamydomonas reinhardtiiChromatinChromosomesCloning, MolecularDNA, ProtozoanGene DosageGene Expression RegulationGenes, ProtozoanGenetic LinkageHistonesMolecular Sequence DataMultigene FamilyNucleosomesRestriction MappingRNA, MessengerRNA, ProtozoanSequence Analysis, DNAConceptsUni linkage groupHistone genesReplication-dependent histonesGene-specific probesNuclease protection experimentsAmino acid sequenceBasal body complexH4 genesHigher eukaryotesGenomic organizationHistone proteinsH3-H4Nucleosome structureLinkage groupsChlamydomonas reinhardtiiSouthern analysisAcid sequenceNorthern analysisProtection experimentsGenomic sequencingGenesBanding patternsNorthern blotS phaseChromosomes
1994
The Chlamydomonas FLA10 gene encodes a novel kinesin-homologous protein.
Walther Z, Vashishtha M, Hall JL. The Chlamydomonas FLA10 gene encodes a novel kinesin-homologous protein. Journal Of Cell Biology 1994, 126: 175-188. PMID: 8027176, PMCID: PMC2120091, DOI: 10.1083/jcb.126.1.175.Peer-Reviewed Original ResearchMeSH KeywordsAlgal ProteinsAmino Acid SequenceAnimalsBase SequenceCell CycleChlamydomonas reinhardtiiCloning, MolecularFlagellaGenes, ProtozoanKinesinsMicrotubule-Associated ProteinsMolecular Sequence DataMorphogenesisProtozoan ProteinsRestriction MappingRNA, MessengerSequence Analysis, DNASequence Homology, Amino AcidConceptsFlagellar assemblyAmino-terminal motor domainUni linkage groupCarboxy-terminal tailKinesin heavy chainTemperature-sensitive defectKinesin-related proteinCentral pair complexMotility mutantsMouse geneLinkage groupsCell divisionFla genesGene productsGenomic DNAFlagellar apparatusNovel roleWestern blot analysisGenesSynchronized culturesNucleotide sequencingAMP-PNPMolecular analysisAxonemeFLA10
1988
slit: An EGF-homologous locus of D. melanogaster involved in the development of the embryonic central nervous system
Rothberg J, Hartley D, Walther Z, Artavanis-Tsakonas S. slit: An EGF-homologous locus of D. melanogaster involved in the development of the embryonic central nervous system. Cell 1988, 55: 1047-1059. PMID: 3144436, DOI: 10.1016/0092-8674(88)90249-8.Peer-Reviewed Original ResearchConceptsEmbryonic central nervous systemD. melanogasterDeduced protein sequenceCentral nervous systemMidline glial cellsLongitudinal axon tractsEGF-like repeatsHigh-level expressionMolecular dataNervous systemProtein sequencesLoci resultsFamily of lociExtracellular localizationLevel expressionLociMelanogasterSitu hybridizationAxon tractsGenesEmbryosGlial cellsAntibody stainingPossible roleSequence