2018
Axon Regeneration: Antagonistic Signaling Pairs in Neuronal Polarization
Hapak SM, Ghosh S, Rothlin CV. Axon Regeneration: Antagonistic Signaling Pairs in Neuronal Polarization. Trends In Molecular Medicine 2018, 24: 615-629. PMID: 29934283, DOI: 10.1016/j.molmed.2018.05.007.BooksMeSH KeywordsAnimalsAxonsCentral Nervous SystemHumansNeuronsRecovery of FunctionRegenerationSignal TransductionSpinal Cord InjuriesPAR3–PAR6–atypical PKC polarity complex proteins in neuronal polarization
Hapak SM, Rothlin CV, Ghosh S. PAR3–PAR6–atypical PKC polarity complex proteins in neuronal polarization. Cellular And Molecular Life Sciences 2018, 75: 2735-2761. PMID: 29696344, PMCID: PMC11105418, DOI: 10.1007/s00018-018-2828-6.BooksConceptsPar3-Par6Neuronal polarityNeuronal polarizationPolarity complex proteinsAPKC kinase activityEukaryotic cell typesProtein complexesComplex proteinsKinase activityPar6APKCSignaling mechanismCell typesPar3Effector moleculesProteinImportant roleEffector functionsPolarityComplexesFundamental featuresPathwayRoleAssemblyCells
2017
TAM receptor tyrosine kinases as emerging targets of innate immune checkpoint blockade for cancer therapy
Akalu YT, Rothlin CV, Ghosh S. TAM receptor tyrosine kinases as emerging targets of innate immune checkpoint blockade for cancer therapy. Immunological Reviews 2017, 276: 165-177. PMID: 28258690, PMCID: PMC5381815, DOI: 10.1111/imr.12522.BooksMeSH KeywordsAdaptive ImmunityAnimalsAntibodies, MonoclonalAxl Receptor Tyrosine KinaseC-Mer Tyrosine KinaseCostimulatory and Inhibitory T-Cell ReceptorsDrug Therapy, CombinationHumansImmunity, InnateImmunotherapyNeoplasmsProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSignal TransductionTumor EscapeConceptsCheckpoint blockadeAdaptive anti-tumor immune responsesT cell checkpoint blockadeT-cell checkpoint inhibitorsAnti-tumor immune responseInnate immune cell functionDendritic cell activityInnate immune checkpointImmune checkpoint blockadeSubset of patientsInnate immune cellsAnti-tumoral immunityProduction of chemokinesImmune cell functionMode of treatmentTAM receptor tyrosine kinasesTremendous clinical successCheckpoint inhibitorsImmune checkpointsCancer immunotherapyUnresponsive patientsImmune cellsT cellsImmune responseAdaptive immunity
2015
Endosomal regulation of contact inhibition through the AMOT:YAP pathway
Cox CM, Mandell EK, Stewart L, Lu R, Johnson DL, McCarter SD, Tavares A, Runyan R, Ghosh S, Wilson JM. Endosomal regulation of contact inhibition through the AMOT:YAP pathway. Molecular Biology Of The Cell 2015, 26: 2673-2684. PMID: 25995376, PMCID: PMC4501364, DOI: 10.1091/mbc.e15-04-0224.Peer-Reviewed Original ResearchConceptsEndosomal membranesYAP activitySubconfluent cellsOrgan growth controlTranscription coactivator YesPhosphorylation-dependent regulationIntegral membrane proteinsConfluent cellsAmot proteinsEndosomal regulationContact-mediated inhibitionCytoplasmic domainEndotubinMembrane proteinsOvergrowth phenotypeInduces translocationAngiomotinYAP interactionDirect bindingGrowth controlContact inhibitionFamily membersCell growthYAPYAP pathwayTAM Receptor Signaling in Immune Homeostasis
Rothlin CV, Carrera-Silva EA, Bosurgi L, Ghosh S. TAM Receptor Signaling in Immune Homeostasis. Annual Review Of Immunology 2015, 33: 1-37. PMID: 25594431, PMCID: PMC4491918, DOI: 10.1146/annurev-immunol-032414-112103.BooksMeSH KeywordsAnimalsDisease SusceptibilityHomeostasisHumansImmunityLigandsReceptor Protein-Tyrosine KinasesSignal TransductionConceptsImmune homeostasisTAM receptor signalingFunction of TAMsResolution of inflammationInnate immune responseTAM receptor tyrosine kinasesImmune settingsAutoimmune diseasesImmune responseInfectious diseasesVascular integrityReceptor tyrosine kinasesReceptor signalingDiseaseApoptotic cellsTyrosine kinaseNegative regulationRecent studiesFunctional importanceHomeostasisEssential roleInflammationCancerAxlMerTK
2014
Targeting aPKC disables oncogenic signaling by both the EGFR and the proinflammatory cytokine TNFα in glioblastoma
Kusne Y, Carrera-Silva EA, Perry AS, Rushing EJ, Mandell EK, Dietrich JD, Errasti AE, Gibbs D, Berens ME, Loftus JC, Hulme C, Yang W, Lu Z, Aldape K, Sanai N, Rothlin CV, Ghosh S. Targeting aPKC disables oncogenic signaling by both the EGFR and the proinflammatory cytokine TNFα in glioblastoma. Science Signaling 2014, 7: ra75. PMID: 25118327, PMCID: PMC4486020, DOI: 10.1126/scisignal.2005196.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinogenesisDrug Delivery SystemsEnzyme-Linked Immunosorbent AssayEpidermal Growth FactorErbB ReceptorsErlotinib HydrochlorideFlow CytometryFluorescent Antibody TechniqueGlioblastomaHumansImmunoblottingImmunohistochemistryImmunoprecipitationKaplan-Meier EstimateMiceNF-kappa BParacrine CommunicationProtein Kinase CQuinazolinesReverse Transcriptase Polymerase Chain ReactionSignal TransductionTumor Necrosis Factor-alphaConceptsAtypical protein kinase CEpidermal growth factor receptorEGFR kinase inhibitorsHuman glioblastoma tumor cellsReceptor tyrosine kinasesProtein kinase CTNFα-dependent activationKinase inhibitorsTranscription factor nuclear factor κBGlioblastoma tumor cellsGrowth factor receptorKinase activityMolecular approachesTyrosine kinaseKinase CNuclear factor κBFactor receptorGlioblastoma microenvironmentFactor κBProinflammatory cytokine TNFαAbundanceTumor necrosis factorGlioblastoma therapyTumor growthGrade IV glioblastomaTyro3, Axl, and Mertk Receptor Signaling in Inflammatory Bowel Disease and Colitis-associated Cancer
Rothlin CV, Leighton JA, Ghosh S. Tyro3, Axl, and Mertk Receptor Signaling in Inflammatory Bowel Disease and Colitis-associated Cancer. Inflammatory Bowel Diseases 2014, 20: 1472-1480. PMID: 24846720, PMCID: PMC4343000, DOI: 10.1097/mib.0000000000000050.BooksConceptsInflammatory bowel diseaseBowel diseaseImmune responseT-cell-dependent adaptive immune responsesApoptotic cellsReceptor tyrosine kinasesProinflammatory cytokine productionSuppression of inflammationAdaptive immune responsesInnate immune responseTAM receptor tyrosine kinasesPotent therapeutic opportunityDisease remissionTyrosine kinaseIntestinal inflammationCytokine productionInflammatory responseLigand Gas6Potent negative regulatorTherapeutic opportunitiesGenetic ablationInflammationProtein SReceptor signalingSuccessful management
2013
Contrasting effects of chronic, systemic treatment with mTOR inhibitors rapamycin and metformin on adult neural progenitors in mice
Kusne Y, Goldberg EL, Parker SS, Hapak SM, Maskaykina IY, Chew WM, Limesand KH, Brooks HL, Price TJ, Sanai N, Nikolich-Zugich J, Ghosh S. Contrasting effects of chronic, systemic treatment with mTOR inhibitors rapamycin and metformin on adult neural progenitors in mice. GeroScience 2013, 36: 199-212. PMID: 23949159, PMCID: PMC3889877, DOI: 10.1007/s11357-013-9572-5.Peer-Reviewed Original ResearchConceptsSystemic administrationMTOR inhibitorsImproved health spanAdult-born neuronsHealth spanEffects of chronicNeural progenitorsAdult neural stem cellsMTOR inhibitor rapamycinInhibition of mTORPotential adverse effectsAdult neural progenitorsNeural stem cellsSystemic treatmentDendate gyrusMouse hippocampusSubventricular regionOrgan functionMetforminBehavioral healthInhibitor rapamycinAdverse effectsPharmacological inhibitorsMTORRapamycinParadoxical role of the proto-oncogene Axl and Mer receptor tyrosine kinases in colon cancer
Bosurgi L, Bernink JH, Cuevas V, Gagliani N, Joannas L, Schmid ET, Booth CJ, Ghosh S, Rothlin CV. Paradoxical role of the proto-oncogene Axl and Mer receptor tyrosine kinases in colon cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 13091-13096. PMID: 23878224, PMCID: PMC3740859, DOI: 10.1073/pnas.1302507110.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisAxl Receptor Tyrosine KinaseAzoxymethaneC-Mer Tyrosine KinaseColitisColonColonic NeoplasmsCytokinesDextran SulfateFemaleFlow CytometryGene ExpressionMacrophagesMaleMiceMice, Inbred StrainsMice, KnockoutMucous MembraneNeutrophilsPhagocytosisProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesReverse Transcriptase Polymerase Chain ReactionSignal TransductionConceptsTumor-promoting environmentMer receptor tyrosine kinaseSystemic anticancer therapyDextran sulfate sodiumAnticancer therapyIntestinal lamina propriaAnti-inflammatory functionsInflammation-associated cancerPotential adverse effectsInflammatory signatureDendritic cellsSulfate sodiumIntestinal macrophagesProinflammatory cytokinesLamina propriaColon cancerTherapeutic targetingOncogenic roleMer inhibitorsApoptotic neutrophilsAxlMultiple cancer hallmarksReceptor tyrosine kinasesTumor cellsAdverse effectsT Cell-Derived Protein S Engages TAM Receptor Signaling in Dendritic Cells to Control the Magnitude of the Immune Response
Silva E, Chan PY, Joannas L, Errasti AE, Gagliani N, Bosurgi L, Jabbour M, Perry A, Smith-Chakmakova F, Mucida D, Cheroutre H, Burstyn-Cohen T, Leighton JA, Lemke G, Ghosh S, Rothlin CV. T Cell-Derived Protein S Engages TAM Receptor Signaling in Dendritic Cells to Control the Magnitude of the Immune Response. Immunity 2013, 39: 160-170. PMID: 23850380, PMCID: PMC4017237, DOI: 10.1016/j.immuni.2013.06.010.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsCells, CulturedColitisCytokinesDendritic CellsFlow CytometryGene ExpressionHumansImmunoblottingLymphocyte ActivationMiceMice, KnockoutMice, TransgenicProtein SReceptor Protein-Tyrosine KinasesReverse Transcriptase Polymerase Chain ReactionSignal TransductionT-LymphocytesConceptsImmune responseDC activationProtein STAM receptor signalingDendritic cell activationExaggerated immune responseTAM receptor tyrosine kinasesDendritic cellsChronic inflammationCostimulatory moleculesImmune homeostasisAdaptive immunityCell activationInnate immunityGenetic ablationReceptor tyrosine kinasesReceptor signalingImmune defenseNegative feedback mechanismMouse TImmunityActivationTyrosine kinaseCellsPROS1
2012
Contribution of PKMζ-dependent and independent amplification to components of experimental neuropathic pain
King T, Qu C, Okun A, Melemedjian OK, Mandell EK, Maskaykina IY, Navratilova E, Dussor GO, Ghosh S, Price TJ, Porreca F. Contribution of PKMζ-dependent and independent amplification to components of experimental neuropathic pain. Pain 2012, 153: 1263-1273. PMID: 22482911, PMCID: PMC3358498, DOI: 10.1016/j.pain.2012.03.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDizocilpine MaleateGyrus CinguliMaleNeuralgiaPeptidesProtein Kinase CRatsRats, Sprague-DawleySignal TransductionSpinal CordSpinal NervesConceptsRostral anterior cingulate cortexExperimental neuropathic painNeuropathic painMK-801Spontaneous painN-methyl-D-aspartate receptor blockadeSpinal nerve ligation injuryNerve ligation injurySpinal dorsal hornLong-term potentiationAnterior cingulate cortexPseudosubstrate inhibitory peptideDorsal hornReceptor blockadeTime-dependent mannerLigation injuryPain processingSingle administrationSpinal cordPainCingulate cortexFull recoveryInhibitory peptidesInhibition of PKMζIndependent mechanisms
2008
Instructive role of aPKCζ subcellular localization in the assembly of adherens junctions in neural progenitors
Ghosh S, Marquardt T, Thaler JP, Carter N, Andrews SE, Pfaff SL, Hunter T. Instructive role of aPKCζ subcellular localization in the assembly of adherens junctions in neural progenitors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 335-340. PMID: 18162555, PMCID: PMC2224213, DOI: 10.1073/pnas.0705713105.Peer-Reviewed Original ResearchConceptsAdherens junctionsNeural progenitorsNeural tubeApical-basal polarityCell fate determinantsNeuronal precursorsApical adherens junctionsApical membranePKCzeta/lambdaCell-cell adhesionChicken neural tubeStem cell proliferationPostmitotic neuronal precursorsAsymmetric inheritanceApical assemblyFate determinantsAsymmetric localizationNeural stem cell proliferationSubcellular compartmentalizationSubcellular localizationNeural stem cellsKinase activityInstructive signalsNeurogenic divisionsInstructive role
2007
TAM Receptors Are Pleiotropic Inhibitors of the Innate Immune Response
Rothlin CV, Ghosh S, Zuniga EI, Oldstone MB, Lemke G. TAM Receptors Are Pleiotropic Inhibitors of the Innate Immune Response. Cell 2007, 131: 1124-1136. PMID: 18083102, DOI: 10.1016/j.cell.2007.10.034.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxl Receptor Tyrosine KinaseC-Mer Tyrosine KinaseDendritic CellsGene Expression RegulationImmunity, InnateInflammationMiceMice, KnockoutOncogene ProteinsProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesReceptor, Interferon alpha-betaSignal TransductionSTAT1 Transcription FactorSuppressor of Cytokine Signaling 1 ProteinSuppressor of Cytokine Signaling 3 ProteinSuppressor of Cytokine Signaling ProteinsToll-Like ReceptorsUbiquitinationConceptsToll-like receptorsDendritic cellsImmune responseChronic inflammatory milieuInnate immune responseTAM receptor tyrosine kinasesRapid inflammatory responseType I interferon receptorCytokine-dependent activationTAM inhibitionTLR inductionInflammatory milieuInflammatory responseProinflammatory pathwaysTAM receptorsTLR signalingPleiotropic inhibitorInflammationReceptor tyrosine kinasesTranscription factor STAT1Interferon receptorEssential stimulatorReceptorsTyrosine kinaseTAM system
2005
Coexpressed EphA Receptors and Ephrin-A Ligands Mediate Opposing Actions on Growth Cone Navigation from Distinct Membrane Domains
Marquardt T, Shirasaki R, Ghosh S, Andrews SE, Carter N, Hunter T, Pfaff SL. Coexpressed EphA Receptors and Ephrin-A Ligands Mediate Opposing Actions on Growth Cone Navigation from Distinct Membrane Domains. Cell 2005, 121: 127-139. PMID: 15820684, DOI: 10.1016/j.cell.2005.01.020.Peer-Reviewed Original ResearchConceptsDistinct membrane domainsMembrane domainsGrowth conesContact-dependent signalingEph receptor tyrosine kinasesReceptor tyrosine kinasesNeuronal growth conesGrowth cone navigationEphA receptorsMotor neuron growth conesSubcellular arrangementGuidance receptorsNeuron growth conesTyrosine kinaseEphrin proteinsReceptor proteinCell typesEphrinProteinPathological processes
2003
Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of β-catenin, and enhanced tumor cell invasion
Lu Z, Ghosh S, Wang Z, Hunter T. Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of β-catenin, and enhanced tumor cell invasion. Cancer Cell 2003, 4: 499-515. PMID: 14706341, DOI: 10.1016/s1535-6108(03)00304-0.Peer-Reviewed Original ResearchMeSH KeywordsBeta CateninCadherinsCaveolaeCaveolin 1CaveolinsCell AdhesionCell MovementCell NucleusCytoskeletal ProteinsDNA-Binding ProteinsDown-RegulationEndocytosisEpidermal Growth FactorErbB ReceptorsGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHumansIntercellular JunctionsNeoplasm MetastasisRNA, AntisenseSignal TransductionSnail Family Transcription FactorsTrans-ActivatorsTranscription FactorsTranscriptional ActivationTumor Cells, CulturedConceptsTranscriptional activityCaveolin-1Cell-cell adhesion proteinsCaveolin-1 functionCell-cell adhesionEGF receptor overexpressionE-cadherinCaveolin-dependent endocytosisTCF/LEFTranscriptional repressor SnailComplex cellular changesCaveolin-1 expressionChronic EGF treatmentTumor cell invasionEGF-induced effectsCaveolin-1 downregulationAdhesion proteinsNegative regulationTranscriptional downregulationAntisense RNAGSK-3betaE-cadherin expressionEGF treatmentHuman tumor cellsCell invasion