2018
aPKCζ-dependent Repression of Yap is Necessary for Functional Restoration of Irradiated Salivary Glands with IGF-1
Chibly AM, Wong WY, Pier M, Cheng H, Mu Y, Chen J, Ghosh S, Limesand KH. aPKCζ-dependent Repression of Yap is Necessary for Functional Restoration of Irradiated Salivary Glands with IGF-1. Scientific Reports 2018, 8: 6347. PMID: 29679075, PMCID: PMC5910385, DOI: 10.1038/s41598-018-24678-4.Peer-Reviewed Original Research
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 erythrocytes
2014
Local Translation and Retrograde Axonal Transport of CREB Regulates IL-6-Induced Nociceptive Plasticity
Melemedjian OK, Tillu DV, Moy JK, Asiedu MN, Mandell EK, Ghosh S, Dussor G, Price TJ. Local Translation and Retrograde Axonal Transport of CREB Regulates IL-6-Induced Nociceptive Plasticity. Molecular Pain 2014, 10: 1744-8069-10-45. PMID: 24993495, PMCID: PMC4091745, DOI: 10.1186/1744-8069-10-45.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonal TransportBrain-Derived Neurotrophic FactorCells, CulturedColchicineCREB-Binding ProteinDisease Models, AnimalGanglia, SpinalGene Expression RegulationInterleukin-6MaleMiceMice, Inbred ICRNociceptive PainNocodazoleProtein TransportQuinazolinonesSciatic NerveSensory Receptor CellsTubulin ModulatorsConceptsCyclic AMP response element binding proteinDorsal root gangliaInterleukin-6Retrograde axonal transportNerve growth factorHyperalgesic primingMechanical hypersensitivityAxonal transportNociceptive plasticitySensory neuronsRetrograde transportExpression of BDNFPrimary sensory neuronsExpression of CREBHr post injectionIL-6 treatmentAxonal traffickingActivity-dependent translationAMP response element binding proteinResponse element-binding proteinCREB DNA bindingIntrathecal injectionHindpaw injectionNociceptive sensitizationInflammatory model
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 effectsmTORC1 inhibition induces pain via IRS-1-dependent feedback activation of ERK
Melemedjian OK, Khoutorsky A, Sorge RE, Yan J, Asiedu MN, Valdez A, Ghosh S, Dussor G, Mogil JS, Sonenberg N, Price TJ. mTORC1 inhibition induces pain via IRS-1-dependent feedback activation of ERK. Pain 2013, 154: 1080-1091. PMID: 23607966, PMCID: PMC3742001, DOI: 10.1016/j.pain.2013.03.021.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDown-RegulationEnzyme ActivationFeedback, PhysiologicalInsulin Receptor Substrate ProteinsMaleMAP Kinase Signaling SystemMechanistic Target of Rapamycin Complex 1MiceMice, Inbred C57BLMice, Inbred ICRMultiprotein ComplexesPainRatsRats, Sprague-DawleySensory Receptor CellsSirolimusTOR Serine-Threonine KinasesConceptsSpontaneous painMechanical hypersensitivitySensory neuronsDevelopment of painPotential treatment optionSensory neuron sensitizationRapamycin complex 1 (mTORC1) inhibitorsExtracellular signal-regulated kinase (ERK) pathwaySignal-regulated kinase pathwaySuppression of S6K1Chronic treatmentPain conditionsPain therapeuticsTransplant rejectionAdenosine monophosphate-activated protein kinase (AMPK) activatorProtein kinase activatorsTreatment optionsAntidiabetic drugsPainSensory hypersensitivityMTOR pathwayNegative feedback loopCertain cancersMammalian targetMTORC1 inhibitionBDNF Regulates Atypical PKC at Spinal Synapses to Initiate and Maintain a Centralized Chronic Pain State
Melemedjian OK, Tillu DV, Asiedu MN, Mandell EK, Moy JK, Blute VM, Taylor CJ, Ghosh S, Price TJ. BDNF Regulates Atypical PKC at Spinal Synapses to Initiate and Maintain a Centralized Chronic Pain State. Molecular Pain 2013, 9: 1744-8069-9-12. PMID: 23510079, PMCID: PMC3608966, DOI: 10.1186/1744-8069-9-12.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain-Derived Neurotrophic FactorCalcium-Calmodulin-Dependent Protein Kinase Type 2Cerebral CortexChronic PainEukaryotic Initiation Factor-4FExtracellular Signal-Regulated MAP KinasesMaleMAP Kinase Signaling SystemMiceMice, Inbred ICRMitogen-Activated Protein Kinase KinasesModels, BiologicalPhosphorylationPosterior Horn CellsProtein BiosynthesisProtein Kinase CProtein TransportSynapsesTime FactorsTOR Serine-Threonine KinasesConceptsChronic pain statesPain statesPersistent nociceptive sensitizationSpinal synapsesChronic painNociceptive sensitizationPotential therapeutic targetImportant medical problemNeurotrophic factorBDNF regulationPersistent sensitizationBDNFTherapeutic targetMedical problemsPainNovel therapeuticsEssential mediatorSensitizationPermanent reversalSynapsesMolecular linkPKMζKey regulator
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 ResearchConceptsRostral 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
2011
Spinal Protein Kinase M ζ Underlies the Maintenance Mechanism of Persistent Nociceptive Sensitization
Asiedu MN, Tillu DV, Melemedjian OK, Shy A, Sanoja R, Bodell B, Ghosh S, Porreca F, Price TJ. Spinal Protein Kinase M ζ Underlies the Maintenance Mechanism of Persistent Nociceptive Sensitization. Journal Of Neuroscience 2011, 31: 6646-6653. PMID: 21543593, PMCID: PMC3090264, DOI: 10.1523/jneurosci.6286-10.2011.Peer-Reviewed Original ResearchConceptsLate long-term potentiationInterleukin-6Intraplantar injectionPersistent nociceptive sensitizationIntrathecal injectionNociceptive sensitizationResolution of hypersensitivitySpinal dorsal hornClinical pain disordersProtein kinase M ζLong-term potentiationAllodynic statePlantar incisionDorsal hornPain pathwaysPain statesAgonist injectionPain disordersAgonist DHPGNocifensive behaviorNocifensive responsesPKMζ inhibitorSpinal cordAllodyniaTherapeutic benefit