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 roleDegenerationMerTKImmunityCell 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 ResearchInflammation of the retinal pigment epithelium drives early-onset photoreceptor degeneration in Mertk-associated retinitis pigmentosa
Mercau M, Akalu Y, Mazzoni F, Gyimesi G, Alberto E, Kong Y, Hafler B, Finnemann S, Rothlin C, Ghosh S. Inflammation of the retinal pigment epithelium drives early-onset photoreceptor degeneration in Mertk-associated retinitis pigmentosa. Science Advances 2023, 9: eade9459. PMID: 36662852, PMCID: PMC9858494, DOI: 10.1126/sciadv.ade9459.Peer-Reviewed Original ResearchConceptsRetinal pigment epitheliumEarly-onset photoreceptor degenerationPR degenerationPigment epitheliumPhotoreceptor degenerationMERTK-associated retinitis pigmentosaJAK1/2 inhibitor ruxolitinibMicroglia activationMonocyte infiltrationInhibitor ruxolitinibMouse modelInflammationLoss of functionDefective phagocytosisInflammation drivesRetinitis pigmentosaDegenerationHypomorphic expressionMiceEpitheliumPhagocytosisRuxolitinibPigmentosaSeverity
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 ResearchStem cells tightly regulate dead cell clearance to maintain tissue fitness
Stewart K, Abdusselamoglu M, Tierney M, Gola A, Hur Y, Gonzales K, Yuan S, Bonny A, Yang Y, Infarinato N, Cowley C, Levorse J, Pasolli H, Ghosh S, Rothlin C, Fuchs E. Stem cells tightly regulate dead cell clearance to maintain tissue fitness. Nature 2024, 633: 407-416. PMID: 39169186, PMCID: PMC11390485, DOI: 10.1038/s41586-024-07855-6.Peer-Reviewed Original ResearchStem cellsImmune-privileged nicheHair follicle stem cellsStem cell functionFollicle stem cellsTissue fitnessMesenchymal tissue cellsBillions of cellsDendritic cellsTissue stemProgenitor cellsPreserving tissue integrityDead cell clearanceClearance genesCell clearanceCell functionFunctional evidenceDying cellsHealthy counterpartsCell deathNon-motileTissue cellsHair cycleProfessional phagocytesApoptotic corpsesThe amalgam of naive CD4+ T cell transcriptional states is reconfigured by helminth infection to dampen the amplitude of the immune response
Even Z, Meli A, Tyagi A, Vidyarthi A, Briggs N, de Kouchkovsky D, Kong Y, Wang Y, Waizman D, Rice T, De Kumar B, Wang X, Palm N, Craft J, Basu M, Ghosh S, Rothlin C. The amalgam of naive CD4+ T cell transcriptional states is reconfigured by helminth infection to dampen the amplitude of the immune response. Immunity 2024, 57: 1893-1907.e6. PMID: 39096910, PMCID: PMC11421571, DOI: 10.1016/j.immuni.2024.07.006.Peer-Reviewed Original ResearchT cell receptorImmune responseNaive CD4<sup>+</sup> T cellsCD4<sup>+</sup> T cellsIFN-IHelminth infectionsNippostrongylus brasiliensis infectionDecreased immune responseType I interferonNaive TT cellsMemory-likeUnrelated antigensTranscriptional changesExtracellular matrixSPF miceCell receptorsI interferonGerm-freeResponse to certain environmental cuesInfectionMiceFunctional changesCell transcriptional statesTranscriptional heterogeneityIn 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 cellsAllelesTREM2 function in glioblastoma immune microenvironment: Can we distinguish reality from illusion?
Ghosh S, Rothlin C. TREM2 function in glioblastoma immune microenvironment: Can we distinguish reality from illusion? Neuro-Oncology 2024, 26: 840-842. PMID: 38290471, PMCID: PMC11066908, DOI: 10.1093/neuonc/noae019.Peer-Reviewed Original Research
2023
Effector response to necroptotic cell death: an ensemble of immune and stromal cells.
Hughes L, Altun O, Nevin J, Wang M, Kluger Y, Pelorosso F, Leighton J, Rothlin C, Ghosh S. Effector response to necroptotic cell death: an ensemble of immune and stromal cells. The Journal Of Immunology 2023, 210: 72.39-72.39. DOI: 10.4049/jimmunol.210.supp.72.39.Peer-Reviewed Original ResearchApoptotic cell deathCell deathGene expression programsEffector responsesNecroptotic cell deathSingle-cell levelMyofibroblast transitionExpression programsStromal cellsTissue renewalTranscriptomic changesCellular corpsesInflammatory bowel diseaseExcessive inflammatory responseInfluence of TGFChemo-genetic approachNon-resolving inflammationMolecular pathwaysResolution of inflammationEssential roleMajor stromal cellsBowel diseaseInflammatory responseInjury modelHelminth infectionsAge-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
2022
Regulation of bone homeostasis by MERTK and TYRO3
Engelmann J, Zarrer J, Gensch V, Riecken K, Berenbrok N, Luu T, Beitzen-Heineke A, Vargas-Delgado M, Pantel K, Bokemeyer C, Bhamidipati S, Darwish I, Masuda E, Burstyn-Cohen T, Alberto E, Ghosh S, Rothlin C, Hesse E, Taipaleenmäki H, Ben-Batalla I, Loges S. Regulation of bone homeostasis by MERTK and TYRO3. Nature Communications 2022, 13: 7689. PMID: 36509738, PMCID: PMC9744875, DOI: 10.1038/s41467-022-33938-x.Peer-Reviewed Original ResearchConceptsCancer-induced bone lossBone homeostasisBone lossBone-resorbing osteoclastsBone metastasesProlong survivalOsteoanabolic therapyMultiple myelomaLung cancerBone-forming osteoblastsBone massHealthy micePreclinical modelsOsteoblast numberMerTKTyro3Bone formationMicePotent regulatorCell type-specific functionsFine equilibriumBlockadeCancerHomeostasisOsteoblast differentiation
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 NordiskHighlights from the Literature
Charest A, Ghosh S, Purow B, Soffietti R. Highlights from the Literature. Neuro-Oncology 2021, 23: 1631-1633. PMCID: PMC8485431, DOI: 10.1093/neuonc/noab201.Commentaries, Editorials and LettersHighlights from the Literature
Abounader R, Charest A, Gerstner E, Ghosh S, Soffietti R. Highlights from the Literature. Neuro-Oncology 2021, 23: 715-717. PMCID: PMC8099462, DOI: 10.1093/neuonc/noab074.Commentaries, Editorials and LettersHighlights from the Literature
Viapiano M, Khasraw M, Huse J, Ghosh S, Niclou S, Golebiewska A. Highlights from the Literature. Neuro-Oncology 2021, 23: 877-880. PMCID: PMC8168813, DOI: 10.1093/neuonc/noab086.Commentaries, Editorials and LettersHighlights from the Literature
Viapiano M, Ghosh S, Soffietti R, Abounader R, Huse J. Highlights from the Literature. Neuro-Oncology 2021, 23: 352-355. PMCID: PMC7992891, DOI: 10.1093/neuonc/noab043.Commentaries, Editorials and Letters
2020
Highlights from the Literature
Purow B, Wright K, Abounader R, Ghosh S, Charest A. Highlights from the Literature. Neuro-Oncology 2020, 22: 1725-1727. PMCID: PMC7746924, DOI: 10.1093/neuonc/noaa246.Commentaries, Editorials and LettersHighlights from the Literature
Soffietti R, Viapiano M, Hegi M, Ghosh S, Purow B. Highlights from the Literature. Neuro-Oncology 2020, 22: 1564-1567. PMCID: PMC7690345, DOI: 10.1093/neuonc/noaa220.Commentaries, Editorials and Letters