Featured Publications
Cell death in development, maintenance, and diseases of the nervous system
Mercau ME, Patwa S, Bhat KPL, Ghosh S, Rothlin CV. Cell death in development, maintenance, and diseases of the nervous system. Seminars In Immunopathology 2022, 44: 725-738. PMID: 35508671, DOI: 10.1007/s00281-022-00938-4.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCell deathTissue-level responsesNervous system homeostasisNervous systemCentral nervous system tumorsMolecular modalitiesAcute brain injuryNervous system tumorsChronic neurodegenerative diseasesSystem homeostasisDead cellsNew therapeutic strategiesNeurodegenerative diseasesMechanisms of disposalGlial cellsNovel understandingAdult neurogenesisSystem tumorsBrain injuryPathological responseDisease statesTherapeutic strategiesCellsRecent studiesDeathDNA methylation of the promoter region at the CREB1 binding site is a mechanism for the epigenetic regulation of brain-specific PKMζ
Pramio D, Vieceli F, Varella-Branco E, Goes C, Kobayashi G, da Silva Pelegrina D, de Moraes B, El Allam A, De Kumar B, Jara G, Farfel J, Bennett D, Kundu S, Viapiano M, Reis E, de Oliveira P, Dos Santos E Passos-Bueno M, Rothlin C, Ghosh S, Schechtman D. DNA methylation of the promoter region at the CREB1 binding site is a mechanism for the epigenetic regulation of brain-specific PKMζ. Biochimica Et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 2023, 1866: 194909. PMID: 36682583, PMCID: PMC10037092, DOI: 10.1016/j.bbagrm.2023.194909.Peer-Reviewed Original ResearchConceptsInduced pluripotent stem cellsInternal promoterNeuronal differentiationEpigenetic mechanismsDNA methylationUpstream promoterProtein kinase C ζHuman neuronal differentiationSite-specific hypermethylationAberrant DNA hypermethylationPluripotent stem cellsEpigenetic regulationSame epigenetic mechanismsLong-term memory formationDNA hypermethylationDemethylated regionsEpigenetic factorsPromoter regionTissue specificityMolecular mechanismsPRKCZ geneDifferentiated neuronsPromoterProtein kinase M zetaLong-term potentiationWhen aging gets on the way of disposal: Senescent cell suppression of efferocytosis
Rothlin C, Ghosh S. When aging gets on the way of disposal: Senescent cell suppression of efferocytosis. Journal Of Cell Biology 2023, 222: e202212023. PMID: 36602762, PMCID: PMC9827511, DOI: 10.1083/jcb.202212023.Peer-Reviewed Original Research
2024
Feeding the wrath with myelin
Ghosh S, Rothlin C. Feeding the wrath with myelin. Trends In Immunology 2024, 45: 729-731. PMID: 39341708, PMCID: PMC11471388, DOI: 10.1016/j.it.2024.09.004.Peer-Reviewed Original Research
2023
Age-dependent differences in efferocytosis determine the outcome of opsonophagocytic protection from invasive pathogens
Bee G, Lokken-Toyli K, Yeung S, Rodriguez L, Zangari T, Anderson E, Ghosh S, Rothlin C, Brodin P, Khanna K, Weiser J. Age-dependent differences in efferocytosis determine the outcome of opsonophagocytic protection from invasive pathogens. Immunity 2023, 56: 1255-1268.e5. PMID: 37059107, PMCID: PMC10330046, DOI: 10.1016/j.immuni.2023.03.018.Peer-Reviewed Original ResearchConceptsAge-dependent differencesNeonatal neutrophilsEarly lifeModulation of CD11bCD11b surface expressionAge-dependent susceptibilitySpn infectionPeripheral bloodMore CD11bMouse modelInfection outcomesStreptococcus pneumoniaeNeutrophilsCD11bEfferocytosisSystemic expressionSurface expressionNeonatesOpsonophagocytosisInvasive pathogensOutcomesPopulation levelCD169PathogensExpression
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 delayRoleHomeostasisAstrocytesLifting the innate immune barriers to antitumor immunity
Rothlin CV, Ghosh S. Lifting the innate immune barriers to antitumor immunity. Journal For ImmunoTherapy Of Cancer 2020, 8: e000695. PMID: 32273348, PMCID: PMC7254113, DOI: 10.1136/jitc-2020-000695.BooksConceptsImmune responseImmune systemInnate immunityT-cell checkpoint inhibitorsMyeloid-derived suppressor cellsInnate immune cell functionBenefit of immunotherapyNatural killer cellsT cell activityInnate immune barrierInnate immune cellsT cell checkpointAnticancer immune responseAdaptive immune responsesImmune cell functionActivated T cellsAnticancer treatment modalitiesLarger patient poolCheckpoint inhibitorsAntitumor immunitySuppressor cellsDendritic cellsPD-L1Exaggerated inflammationKiller cells
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/scarringBringing on the itch
Waizman DA, Ghosh S, Rothlin CV. Bringing on the itch. ELife 2019, 8: e52931. PMID: 31782733, PMCID: PMC6884404, DOI: 10.7554/elife.52931.BooksCracking the Cell Death Code
Rothlin CV, Ghosh S. Cracking the Cell Death Code. Cold Spring Harbor Perspectives In Biology 2019, 12: a036343. PMID: 31548182, PMCID: PMC7197433, DOI: 10.1101/cshperspect.a036343.Peer-Reviewed Original ResearchInduction of sterile type 2 inflammation
de Kouchkovsky DA, Ghosh S, Rothlin CV. Induction of sterile type 2 inflammation. Nature Materials 2019, 18: 193-194. PMID: 30783225, PMCID: PMC7081377, DOI: 10.1038/s41563-019-0300-0.Commentaries, Editorials and Letters
2018
Cenabis Bene: Treg Cells Invite Macrophages to Dine
Hughes LD, Ghosh S, Rothlin CV. Cenabis Bene: Treg Cells Invite Macrophages to Dine. Immunity 2018, 49: 579-582. PMID: 30332622, DOI: 10.1016/j.immuni.2018.10.002.Commentaries, Editorials and LettersCoagulopathies and inflammatory diseases: ‘…glimpse of a Snark’
del Carmen S, Hapak SM, Ghosh S, Rothlin CV. Coagulopathies and inflammatory diseases: ‘…glimpse of a Snark’. Current Opinion In Immunology 2018, 55: 44-53. PMID: 30268838, PMCID: PMC6366937, DOI: 10.1016/j.coi.2018.09.005.BooksConceptsAnti-pathogen defenseUnderlying molecular basisInflammatory diseasesMolecular basisSelective pressureHost defense mechanismsSubset of patientsDefense mechanismsVertebratesRegulation of inflammationHuman populationThrombophilic stateTherapeutic roleDefenseDiseaseInvertebratesCoagulopathyInflammationPhysical injuryMutationsRegulationPathogensCascadeApixabanThrombophiliaAxon 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.BooksPAR3–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
Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage
Chang CF, Goods BA, Askenase MH, Hammond MD, Renfroe SC, Steinschneider AF, Landreneau MJ, Ai Y, Beatty HE, da Costa LHA, Mack M, Sheth KN, Greer DM, Huttner A, Coman D, Hyder F, Ghosh S, Rothlin CV, Love JC, Sansing LH. Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage. Journal Of Clinical Investigation 2017, 128: 607-624. PMID: 29251628, PMCID: PMC5785262, DOI: 10.1172/jci95612.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisAxl Receptor Tyrosine KinaseBrain InjuriesCerebral HemorrhageC-Mer Tyrosine KinaseErythrocytesHematomaHumansImmunity, InnateInflammationMacrophagesMaleMiceMice, Inbred C57BLMice, TransgenicPhagocytosisPhenotypeProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSolubilityTreatment OutcomeConceptsMonocyte-derived macrophagesIntracerebral hemorrhageEryptotic erythrocytesNeurological recoveryHematoma clearanceExperimental intracerebral hemorrhageReceptor tyrosine kinase AXLHuman monocyte-derived macrophagesTyrosine kinase AXLICH onsetFunctional outcomeBrain injuryTissue injurySoluble AxlDynamic phenotypic changesAlternative activationPhenotypic changesMacrophage phenotypeIron depositionMurine brainMacrophage responseRestorative functionEfferocytosisMacrophagesEngulfment of erythrocytesDeath begets a new beginning
Bosurgi L, Hughes LD, Rothlin CV, Ghosh S. Death begets a new beginning. Immunological Reviews 2017, 280: 8-25. PMID: 29027219, PMCID: PMC5658037, DOI: 10.1111/imr.12585.BooksConceptsCell deathBillions of cellsApoptotic cell deathEnvironmental cuesSpecific functionsHomeostatic conditionsTissue microenvironmentApoptotic cellsDead cellsTissue repairGrowth factorCellsPhagocytosisPerpetual featureSevere tissue injuryDeathInductionAppropriate responseMicroenvironmentPhagocytesCuesThe 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 activityInflammationCancerTAM 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 immunityNegative Regulation of Type 2 Immunity
de Kouchkovsky DA, Ghosh S, Rothlin CV. Negative Regulation of Type 2 Immunity. Trends In Immunology 2017, 38: 154-167. PMID: 28082101, PMCID: PMC5510550, DOI: 10.1016/j.it.2016.12.002.BooksConceptsType 2 immunityProtective host responseType 2 responsesAllergic rhinitisAtopic diseasesAtopic dermatitisMillions of individualsHost responseImmune systemImmunityInappropriate activationNegative regulationEnvironmental substancesParasitic helminthsIndustrialized worldHelminthsRhinitisImmunopathologyKey playersAsthmaDermatitisAllergensDiseaseIndividuals