Featured Publications
Tissue-specific modifier alleles determine Mertk loss-of-function traits
Akalu YT, Mercau ME, Ansems M, Hughes LD, Nevin J, Alberto EJ, Liu XN, He LZ, Alvarado D, Keler T, Kong Y, Philbrick WM, Bosenberg M, Finnemann SC, Iavarone A, Lasorella A, Rothlin CV, Ghosh S. Tissue-specific modifier alleles determine Mertk loss-of-function traits. ELife 2022, 11: e80530. PMID: 35969037, PMCID: PMC9433089, DOI: 10.7554/elife.80530.Peer-Reviewed Original ResearchConceptsAnti-tumor immunityKO miceRetinal pigment epitheliumRetinal degenerationPigment epitheliumPro-inflammatory tumor microenvironmentSyngeneic mouse tumor modelsKO mice displayEarly-onset retinal degenerationSevere retinal degenerationMouse tumor modelsFailure of macrophagesKnockout mouse modelPhotoreceptor outer segmentsMouse modelMice displayTumor modelTumor microenvironmentMacrophage phagocytosisReceptor tyrosine kinasesMiceCritical roleDegenerationMerTKImmunity
2024
In the Eyes of the Beholder—New Mertk Knockout Mouse and Re-Evaluation of Phagocytosis versus Anti-Inflammatory Functions of MERTK
Ghosh S, Finnemann S, Vollrath D, Rothlin C. In the Eyes of the Beholder—New Mertk Knockout Mouse and Re-Evaluation of Phagocytosis versus Anti-Inflammatory Functions of MERTK. International Journal Of Molecular Sciences 2024, 25: 5299. PMID: 38791338, PMCID: PMC11121519, DOI: 10.3390/ijms25105299.Peer-Reviewed Original ResearchReceptor tyrosine kinasesFamily of receptor tyrosine kinasesTAM family of receptor tyrosine kinasesEarly-onset photoreceptor degenerationKnockout mouse modelMolecular functionsNegative regulator of inflammationKnockout phenotypesNegative regulatorMouse geneticsRegulation of inflammationMolecular approachesEmbryonic stem cellsAnti-inflammatory functionsRetinal degenerationTyrosine kinasePhotoreceptor degenerationKnockout miceKnockout modelsMouse modelRodent modelsTAM familyMerTK functionStem cellsAlleles
2021
Prothrombotic Phenotype of a Protein S Mutant Lacking Anticoagulant Activity
Springborn S, Ghosh S, Schulte M, Rothlin C, Branchford B. Prothrombotic Phenotype of a Protein S Mutant Lacking Anticoagulant Activity. Blood 2021, 138: 2098. DOI: 10.1182/blood-2021-153904.Peer-Reviewed Original ResearchProtein STAM familyPlatelet activationReceptor tyrosine kinasesCremaster muscle microvasculatureProtein CPulmonary embolism modelWild-type littermatesWild-type animalsTyrosine kinaseVascular injuryMuscle microvasculaturePlatelet responsivenessProthrombotic phenotypeInjury siteCoagulation factor VTail veinEmbolism modelHeterozygous littermatesLaser injuryVitamin KHomozygous miceMiceAnticoagulant activityNovo Nordisk
2020
Astrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo
Damisah EC, Hill RA, Rai A, Chen F, Rothlin CV, Ghosh S, Grutzendler J. Astrocytes and microglia play orchestrated roles and respect phagocytic territories during neuronal corpse removal in vivo. Science Advances 2020, 6: eaba3239. PMID: 32637606, PMCID: PMC7319765, DOI: 10.1126/sciadv.aba3239.Peer-Reviewed Original ResearchConceptsCorpse removalPrecise spatiotemporal resolutionApoptotic cell removalReceptor tyrosine kinasesGlial cellsOrchestrated rolesTyrosine kinaseApoptotic bodiesCell deathSpecialized roleCoordinated interactionPhagocytic interactionSingle cellsBrain homeostasisCellsCell removalIntravital optical imagingSpatiotemporal resolutionRole of phagocytesSynchronized fashionKinaseMarked delayRoleHomeostasisAstrocytes
2019
Funerals and Feasts: The Immunological Rites of Cell Death.
Galimberti VE, Rothlin CV, Ghosh S. Funerals and Feasts: The Immunological Rites of Cell Death. The Yale Journal Of Biology And Medicine 2019, 92: 663-674. PMID: 31866781, PMCID: PMC6913811.BooksConceptsReceptor tyrosine kinasesCell deathMolecular mechanismsCell death modalitiesUnscheduled cell deathNon-self recognitionImportant negative regulatorDead cellsMulticellular organismsAdult organismDeath modalitiesProper immune responseNegative regulatorTyrosine kinaseMolecular processesInjury/infectionImmune responseMolecular modalitiesOmnipresent processOrganismsDefective developmentMost tissuesImmune system functionTAM familyFibrosis/scarring
2017
The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer
Uribe DJ, Mandell EK, Watson A, Martinez JD, Leighton JA, Ghosh S, Rothlin CV. The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer. PLOS ONE 2017, 12: e0179979. PMID: 28727830, PMCID: PMC5519024, DOI: 10.1371/journal.pone.0179979.Peer-Reviewed Original ResearchConceptsColorectal cancerTAM receptor tyrosine kinasesReceptor tyrosine kinasesLate-stage colorectal cancerColitis-associated cancerStage colorectal cancerAnti-inflammatory effectsReceptor tyrosine kinase AXLTyro3 receptor tyrosine kinasesSufficient therapeutic benefitTyrosine kinase AXLNumber of cancersTYRO3 expressionChronic inflammationAllergic responsesTherapeutic benefitTumor cell migrationImmunological diseasesExpression associatesIndiscriminate inhibitionGene signatureAxlAxl kinase activityInflammationCancer
2016
The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity
Chan PY, Carrera Silva EA, De Kouchkovsky D, Joannas LD, Hao L, Hu D, Huntsman S, Eng C, Licona-Limón P, Weinstein JS, Herbert DR, Craft JE, Flavell RA, Repetto S, Correale J, Burchard EG, Torgerson DG, Ghosh S, Rothlin CV. The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity. Science 2016, 352: 99-103. PMID: 27034374, PMCID: PMC4935984, DOI: 10.1126/science.aaf1358.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsAsthmaBlood ProteinsDendritic CellsDisease Models, AnimalGene Knockout TechniquesHost-Parasite InteractionsHumansImmunity, InnateInterleukin-4MiceMice, Inbred C57BLMice, KnockoutNippostrongylusProtein SPyroglyphidaeReceptor Protein-Tyrosine KinasesStrongylida InfectionsT-LymphocytesConceptsType 2 immunityType 2 responsesType 2 cytokinesHuman dendritic cellsInnate immune cellsDendritic cellsAllergic diseasesImmune cellsT cellsAdaptive immunityInterleukin-4Host responseFunctional neutralizationGenetic ablationReceptor tyrosine kinasesImmunityProtective functionTyro3Tyrosine kinaseNegative regulatorPROS1CellsResponseCytokinesDisease
2015
TAM 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.BooksConceptsImmune 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
Paradoxical 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
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