2025
Pivotal Results of SELECT-MDS-1 Phase 3 Study of Tamibarotene with Azacitidine in Newly Diagnosed Higher-Risk MDS
DeZern A, Thepot S, de Botton S, Patriarca A, Deeren D, Torregrossa-Diaz J, Marconi G, Bernal T, Burgues J, Xicoy B, Jonášová A, Zeidan A, Dimicoli-Salazar S, Simand C, Valcarcel D, Campelo M, Chai-Ho W, Saini L, Garnier A, Geissler K, Ofran Y, Nagy Z, Krishnamurthy P, Lübbert M, Basak G, Carraway H, Sallman D, Borate U, Santini V, Campbell V, Fenaux P, Braun T, Lanza F, Zaucha J, Roth D, Paul S, Roy P, Kelly M, Volkert A, Chisholm J, Malak T, Klimek V, Cluzeau T, Group T. Pivotal Results of SELECT-MDS-1 Phase 3 Study of Tamibarotene with Azacitidine in Newly Diagnosed Higher-Risk MDS. Blood Advances 2025 PMID: 40334070, DOI: 10.1182/bloodadvances.2025016229.Peer-Reviewed Original ResearchHigher-risk MDSIPSS-RBlast count >5%Higher-risk MDS patientsMDS-EB-1Bone marrow blastsPhase 3 studyHigher-risk featuresBlood-based assayGene overexpressionMarrow blastsCR ratePrimary MDSBaseline characteristicsAzacitidineResponse rateNatural historyPatientsTamibaroteneOverexpressionP-valueTreatment effectsExploration of alternative approachesRARAGroupType I Interferon-Induced Modification of Yellow Fever Virus NS5 Enhances Binding to Human STAT2
Laurent-Rolle M, Morrison J. Type I Interferon-Induced Modification of Yellow Fever Virus NS5 Enhances Binding to Human STAT2. Methods In Molecular Biology 2025, 2913: 73-78. PMID: 40249426, DOI: 10.1007/978-1-0716-4458-4_7.Peer-Reviewed Original ResearchConceptsHuman STAT2Yellow fever virusStudy of virus-host interactionsNonstructural protein 5Human signal transducerVirus-host interactionsInnate immune responseNS5 proteinType III interferonsSignal transducerOverexpression techniquesSTAT2Immunoprecipitation methodProtein 5Cell linesIII interferonsFever virusPathogenic virusesTreated with type ITreated with interferonImmune responseVirusImmunoprecipitationNS5OverexpressionA widespread and ancient bacterial machinery assembles cytochrome OmcS nanowires essential for extracellular electron transfer
Shen C, Salazar-Morales A, Jung W, Erwin J, Gu Y, Coelho A, Gupta K, Yalcin S, Samatey F, Malvankar N. A widespread and ancient bacterial machinery assembles cytochrome OmcS nanowires essential for extracellular electron transfer. Cell Chemical Biology 2025, 32: 239-254.e7. PMID: 39818215, PMCID: PMC11845295, DOI: 10.1016/j.chembiol.2024.12.013.Peer-Reviewed Original ResearchConceptsExtracellular electron transferPhylogenetically diverse speciesATP-dependent mannerMicrobial extracellular electron transferBacterial machineryDiverse prokaryotesDiverse speciesBiotechnological applicationsGeobacter sulfurreducensCell growthSurface-displayedMorphology maintenanceBiophysical methodsMulti-heme cytochromesCytochromeElectron transferOsCHSProkaryotesPhylogeneticallySulfurreducensGeobacterOverexpressionSpeciesMachinery
2024
RNA and condensates: Disease implications and therapeutic opportunities
Han T, Portz B, Young R, Boija A, Klein I. RNA and condensates: Disease implications and therapeutic opportunities. Cell Chemical Biology 2024, 31: 1593-1609. PMID: 39303698, DOI: 10.1016/j.chembiol.2024.08.009.Peer-Reviewed Original ResearchConceptsRegulate key cellular processesDiverse RNA speciesRNA speciesTarget RNACompartmentalizing proteinsCellular processesRNA moleculesMembraneless organellesRNA roleBiomolecular condensatesRNA-based therapiesComplex diseasesRNA abnormalitiesRNADisease pathogenesisCondensate formationProperties of condensatesTherapeutic strategiesSmall moleculesOrganellesMislocalizationOverexpressionProteinSpeciesNeurological disordersCentral neurocytoma exhibits radial glial cell signatures with FGFR3 hypomethylation and overexpression
Lee Y, Chowdhury T, Kim S, Yu H, Kim K, Kang H, Kim M, Kim J, Kim Y, Ji S, Hwang K, Han J, Hwang J, Yoo S, Lee K, Choe G, Won J, Park S, Lee Y, Shin J, Park C, Kim C, Kim J. Central neurocytoma exhibits radial glial cell signatures with FGFR3 hypomethylation and overexpression. Experimental & Molecular Medicine 2024, 56: 975-986. PMID: 38609519, PMCID: PMC11059271, DOI: 10.1038/s12276-024-01204-3.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingNeuronal development pathwaysDrivers of tumorigenesisGlial cell differentiationMethylation sequencingGenomic eventsPI3K-Akt activationDownstream eventsGene markersMultiomics approachCell differentiationRadial glial cellsHypomethylationOverexpressionSequenceTumorigenesisFGFR3Cell signaturesGlial cellsPotential roleCellsTumor cellsCentral nervous systemMultiomicsOntogeny
2023
A kinesin-1 adaptor complex controls bimodal slow axonal transport of spectrin in Caenorhabditis elegans
Glomb O, Swaim G, Munoz LLancao P, Lovejoy C, Sutradhar S, Park J, Wu Y, Cason S, Holzbaur E, Hammarlund M, Howard J, Ferguson S, Gramlich M, Yogev S. A kinesin-1 adaptor complex controls bimodal slow axonal transport of spectrin in Caenorhabditis elegans. Developmental Cell 2023, 58: 1847-1863.e12. PMID: 37751746, PMCID: PMC10574138, DOI: 10.1016/j.devcel.2023.08.031.Peer-Reviewed Original ResearchIntegrative genetic and genomic networks identify microRNA associated with COPD and ILD
Pavel A, Garrison C, Luo L, Liu G, Taub D, Xiao J, Juan-Guardela B, Tedrow J, Alekseyev Y, Yang I, Geraci M, Sciurba F, Schwartz D, Kaminski N, Beane J, Spira A, Lenburg M, Campbell J. Integrative genetic and genomic networks identify microRNA associated with COPD and ILD. Scientific Reports 2023, 13: 13076. PMID: 37567908, PMCID: PMC10421936, DOI: 10.1038/s41598-023-39751-w.Peer-Reviewed Original ResearchConceptsSeed sequenceGene expressionShort RNA sequencingAirway differentiationIntegrative network analysisExpression networksRNA sequencingGenomic networksMiRNA regulatorsMiRNA isoformsNotch pathwayIsomiRsDistinct subclustersSNP microarraysGenesMicroRNAsMolecular heterogeneityILD pathogenesisDisease networkOverexpressionSequenceExpressionNetwork analysisDifferentiationGrb2Serendipitous Discovery of T Cell–Produced KLK1b22 as a Regulator of Systemic Metabolism
Arwood M, Sun I, Patel C, Sun I, Oh M, Bettencourt I, Claiborne M, Chan-Li Y, Zhao L, Waickman A, Mavrothalassitis O, Wen J, Aja S, Powell J. Serendipitous Discovery of T Cell–Produced KLK1b22 as a Regulator of Systemic Metabolism. ImmunoHorizons 2023, 7: 493-507. PMID: 37358498, PMCID: PMC10580127, DOI: 10.4049/immunohorizons.2300016.Peer-Reviewed Original ResearchConceptsGlucose toleranceT cellsSystemic metabolismGenome ProjectWild-type T cellsMicroarray analysisCell differentiationNovel roleRhebMammalian targetInsulin receptorT cell differentiationReduced glucose toleranceMarked increaseStrains of miceBeige fatExpressionInsulin sensitivityOverexpressionSystemic overexpressionMetabolismCellsMiceToleranceFurther studiesEctopic RING activity at the ER membrane differentially impacts ERAD protein quality control pathways
Mehrtash A, Hochstrasser M. Ectopic RING activity at the ER membrane differentially impacts ERAD protein quality control pathways. Journal Of Biological Chemistry 2023, 299: 102927. PMID: 36682496, PMCID: PMC9950527, DOI: 10.1016/j.jbc.2023.102927.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulum-associated degradationProtein quality control pathwaysQuality control pathwaysER membraneE3 complexControl pathwaysRING-type E3 ubiquitin ligasesE3 ubiquitin ligasesDominant negative mutantDoa10 substratesMisfolded proteinsUbiquitin ligasesERAD factorsMammalian cellsRING domainUBC6Substrate turnoverLuminal substratesDoa10OverexpressionPathway defectsYeastPathwayRing activityMembrane
2022
Overexpression of UCP3 decreases mitochondrial efficiency in mouse skeletal muscle in vivo
Codella R, Alves TC, Befroy DE, Choi CS, Luzi L, Rothman DL, Kibbey RG, Shulman GI. Overexpression of UCP3 decreases mitochondrial efficiency in mouse skeletal muscle in vivo. FEBS Letters 2022, 597: 309-319. PMID: 36114012, DOI: 10.1002/1873-3468.14494.Peer-Reviewed Original ResearchConceptsOverexpression of UCP3ATP synthesisMitochondrial oxidationMitochondrial transmembrane proteinInner mitochondrial membraneSkeletal muscleMitochondrial oxidative phosphorylationMitochondrial oxidative metabolismMuscle-specific overexpressionMouse skeletal muscleTransmembrane proteinMitochondrial membraneProton leakPrecise functionOxidative phosphorylationMitochondrial efficiencyUCP3 expressionMitochondrial inefficiencyOverexpressionProtein 3UCP3Oxidative metabolismVivoMagnetic resonance spectroscopyPhosphorylationA translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility
Voloudakis G, Vicari J, Venkatesh S, Hoffman G, Dobrindt K, Zhang W, Beckmann N, Higgins C, Argyriou S, Jiang S, Hoagland D, Gao L, Corvelo A, Cho K, Lee K, Bian J, Lee J, Iyengar S, Luoh S, Akbarian S, Striker R, Assimes T, Schadt E, Lynch J, Merad M, tenOever B, Charney A, Brennand K, Fullard J, Roussos P. A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility. Npj Genomic Medicine 2022, 7: 52. PMID: 36064543, PMCID: PMC9441828, DOI: 10.1038/s41525-022-00324-x.Peer-Reviewed Original ResearchCandidate gene targetsGene targetsTranslational genomics approachesHost susceptibilityGenomic approachesGenetic susceptibility variantsGenetic lociDruggable genesGene expressionMolecular pathwaysSusceptibility variantsCOVID-19 susceptibilityGenetic findingsApproach identifiesExpressionCOVID-19 patient bloodCritical next stepGenesLociOverexpressionTargetPathwaySusceptibilityIL10RBRecent effortsIdentification of growth hormone receptor as a relevant target for precision medicine in low‐EGFR expressing glioblastoma
Verreault M, Vilchis I, Rosenberg S, Lemaire N, Schmitt C, Guehennec J, Royer‐Perron L, Thomas J, Lam TT, Dingli F, Loew D, Ducray F, Paris S, Carpentier C, Marie Y, Laigle‐Donadey F, Rousseau A, Pigat N, Boutillon F, Bielle F, Mokhtari K, Frank SJ, de Reyniès A, Hoang‐Xuan K, Sanson M, Goffin V, Idbaih A. Identification of growth hormone receptor as a relevant target for precision medicine in low‐EGFR expressing glioblastoma. Clinical And Translational Medicine 2022, 12: e939. PMID: 35808822, PMCID: PMC9270581, DOI: 10.1002/ctm2.939.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorGrowth hormone receptorPatient-derived cell linesOncogenic mechanismsGene expression profilesCell linesGain of functionHormone receptorsExpression of proteinsCellular movementGrowth factor receptorHuman GBM samplesExpression profilesCell migrationCommon oncogenic mechanismThird of patientsDistinct molecular subsetsGBM samplesPromoter hypermethylationNew therapeutic approachesFactor receptorCell proliferationPharmacological inhibitionRelevant targetsOverexpressionMycobacterium tuberculosis encodes a YhhN family membrane protein with lysoplasmalogenase activity that protects against toxic host lysolipids
Jurkowitz MS, Azad AK, Monsma PC, Keiser TL, Kanyo J, Lam TT, Bell CE, Schlesinger LS. Mycobacterium tuberculosis encodes a YhhN family membrane protein with lysoplasmalogenase activity that protects against toxic host lysolipids. Journal Of Biological Chemistry 2022, 298: 101849. PMID: 35314194, PMCID: PMC9052158, DOI: 10.1016/j.jbc.2022.101849.Peer-Reviewed Original ResearchConceptsMembrane proteinsIntegral membrane proteinsVinyl ether bondHuman macrophagesPathogen Mycobacterium tuberculosisSn-1 positionSubclass of glycerophospholipidsGrowth advantageHost lipidsProteinFatty aldehydesMycobacterium smegmatisPhospholipase ASn-2 carbonSpheroplastsGlycerol backboneCell densityPlasmalogensCellsMycobacterium tuberculosisMacrophagesGenesOverexpressionLysoplasmenylcholinePLPC
2021
Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome
Chandra S, Mannino PJ, Thaller DJ, Ader NR, King MC, Melia TJ, Lusk CP. Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome. Journal Of Cell Biology 2021, 220: e202103030. PMID: 34714326, PMCID: PMC8575018, DOI: 10.1083/jcb.202103030.Peer-Reviewed Original ResearchMeSH KeywordsAutophagosomesAutophagyAutophagy-Related ProteinsCytoplasmic VesiclesGreen Fluorescent ProteinsNuclear EnvelopeProtein DomainsReceptors, Cytoplasmic and NuclearSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsStructure-Activity RelationshipTime FactorsVacuolesVesicular Transport ProteinsConceptsInner nuclear membraneNuclear envelope lumenOuter nuclear membraneNuclear membraneSplit-GFP reporterNuclear envelope localizationINM proteinsAutophagy apparatusEnvelope localizationLumenal vesiclesLumenal domainCargo adaptorsAtg39Sequence elementsCorrelative lightVesiclesAutophagosomesMembraneNucleophagyAdaptorReporterProteinOverexpressionMotifTSC2 regulates lysosome biogenesis via a non-canonical RAGC and TFEB-dependent mechanism
Alesi N, Akl EW, Khabibullin D, Liu HJ, Nidhiry AS, Garner ER, Filippakis H, Lam HC, Shi W, Viswanathan SR, Morroni M, Ferguson SM, Henske EP. TSC2 regulates lysosome biogenesis via a non-canonical RAGC and TFEB-dependent mechanism. Nature Communications 2021, 12: 4245. PMID: 34253722, PMCID: PMC8275687, DOI: 10.1038/s41467-021-24499-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCarcinoma, Renal CellCell NucleusCell ProliferationFemaleGene Expression RegulationHEK293 CellsHeLa CellsHumansKidney NeoplasmsLysosomesMiceMice, Inbred NODMice, SCIDMonomeric GTP-Binding ProteinsOrganelle BiogenesisPhosphorylationPhosphoserineProtein TransportProto-Oncogene ProteinsTranscription, GeneticTuberous Sclerosis Complex 2 ProteinTumor Suppressor ProteinsConceptsTranscription factor EBTSC2-deficient cellsLysosome biogenesisLysosomal biogenesisDeficient cellsRapamycin complex 1TSC1/2 complexTFEB phosphorylationTuberous sclerosis complexTSC proteinsMaster regulatorBiogenesisMechanistic targetRagCCritical regulatorFolliculinPhosphorylationDependent sitesRegulatorProteinOverexpressionTSC2 mutationsCellsGTPaseMTORC1UBX Domain Protein 6 Positively Regulates JAK-STAT1/2 Signaling.
Ketkar H, Harrison A, Graziano V, Geng T, Yang L, Vella A, Wang P. UBX Domain Protein 6 Positively Regulates JAK-STAT1/2 Signaling. The Journal Of Immunology 2021, 206: 2682-2691. PMID: 34021047, PMCID: PMC8164993, DOI: 10.4049/jimmunol.1901337.Peer-Reviewed Original ResearchConceptsTyrosine kinase 2Domain-containing proteinsExpression of hundredsComplex cellular regulationRNA viral replicationJAK/STATCellular regulationType I/III IFNsKinase 2JAK/Type I/III IFNProtein 6IFN expressionGenesViral infectionSignalingExpressionViral replicationExpression of IFNCellsType IProteinSTATOverexpressionDeletionNTRK genomic alterations in Latin-American cancer patients.
Carvajal D, Salas C, Marcelain K, Perez F, Rivas S, Feliu E, Schalper K, Arminsen R. NTRK genomic alterations in Latin-American cancer patients. Journal Of Clinical Oncology 2021, 39: e15088-e15088. DOI: 10.1200/jco.2021.39.15_suppl.e15088.Peer-Reviewed Original ResearchReceptor kinaseIndependent patient seriesChimeric proteinLatin American patientsDownstream signalingOncomine Comprehensive AssayTropomyosin receptor kinaseNTRK1-3Patient seriesTertiary hospitalActionable alterationsFFPE tumor samplesTRK fusionsNGS panelFocus assayTumor samplesComprehensive assayAssaysKinaseGenesSignalingMultiple institutionsOncogeneProteinOverexpressionAcute Myeloid Leukemia Leading to Central Diabetes Insipidus
Wojeck B, Gossmann M, Zeidan A, Inzucchi S. Acute Myeloid Leukemia Leading to Central Diabetes Insipidus. Journal Of The Endocrine Society 2021, 5: a570-a571. PMCID: PMC8090637, DOI: 10.1210/jendso/bvab048.1163.Peer-Reviewed Original ResearchCentral diabetes insipidusAcute myeloid leukemiaLeukemic infiltrationMonosomy 7Antidiuretic hormoneWhite blood cell countEVI-1 overexpressionBlood cell countAML patientsAML casesHypothalamic secretionMyeloid leukemiaDiabetes insipidusCell countPituitary glandNormal plateletsPatientsMolecular evaluationInfiltrationOverexpressionComplicationsAnemiaInsipidusLeukemiaAbnormalitiesTargeted degradation of transcription factors by TRAFTACs: TRAnscription Factor TArgeting Chimeras
Samarasinghe KTG, Jaime-Figueroa S, Burgess M, Nalawansha DA, Dai K, Hu Z, Bebenek A, Holley SA, Crews CM. Targeted degradation of transcription factors by TRAFTACs: TRAnscription Factor TArgeting Chimeras. Cell Chemical Biology 2021, 28: 648-661.e5. PMID: 33836141, PMCID: PMC8524358, DOI: 10.1016/j.chembiol.2021.03.011.Peer-Reviewed Original ResearchConceptsTranscription factorsTargeted degradationTranscription factor degradationDNA-binding proteinsMultiple signaling pathwaysGeneralizable strategyDCas9 proteinProtein familyLigandable sitesProteasomal pathwaySignaling pathwaysOverexpression of oncoproteinsAberrant activationChimeric oligonucleotideProteinChimerasFactor degradationNF-κBPathwayHaloTagDegradationBrachyuryOverexpressionOncoproteinOligonucleotide
2020
Twist2 is NFkB-responsive when p120-catenin is inactivated and EGFR is overexpressed in esophageal keratinocytes
Lehman H, Kidacki M, Stairs D. Twist2 is NFkB-responsive when p120-catenin is inactivated and EGFR is overexpressed in esophageal keratinocytes. Scientific Reports 2020, 10: 18829. PMID: 33139779, PMCID: PMC7608670, DOI: 10.1038/s41598-020-75866-0.Peer-Reviewed Original ResearchConceptsEsophageal squamous cell carcinomaCancer typesYear of diagnosisSquamous cell carcinomaEsophageal keratinocytesOverexpression of EGFRHuman esophageal keratinocytesAggressive cell typesFatal cancer typePoor prognosisCell carcinomaTwist2 expressionEGFR overexpressionEGFREMT-inducing geneNFkBResponsive targetsTwist2Paucity of researchCell typesPresent studyKeratinocytesP120-cateninOverexpressionComplete loss
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