2023
Human nucleolar protein 7 (NOL7) is required for early pre-rRNA accumulation and pre-18S rRNA processing
McCool M, Bryant C, Huang H, Ogawa L, Farley-Barnes K, Sondalle S, Abriola L, Surovtseva Y, Baserga S. Human nucleolar protein 7 (NOL7) is required for early pre-rRNA accumulation and pre-18S rRNA processing. RNA Biology 2023, 20: 257-271. PMID: 37246770, PMCID: PMC10228412, DOI: 10.1080/15476286.2023.2217392.Peer-Reviewed Original ResearchConceptsPre-rRNA accumulationRibosome biogenesisNonessential roleEukaryotic ribosome biogenesisEssential cellular processesNucleolar stress responsePre-rRNA levelsRRNA processingLikely orthologCellular processesAssociated proteinsTumor suppressorStress responseHuman cellsProtein synthesisProtein 7Human counterpartBiogenesisYeastOrthologsHomologSubcomplexAccumulationRRNATranscriptionEngineered cardiac tissue model of restrictive cardiomyopathy for drug discovery
Wang B, Nash T, Zhang X, Rao J, Abriola L, Kim Y, Zakharov S, Kim M, Luo L, Morsink M, Liu B, Lock R, Fleischer S, Tamargo M, Bohnen M, Welch C, Chung W, Marx S, Surovtseva Y, Vunjak-Novakovic G, Fine B. Engineered cardiac tissue model of restrictive cardiomyopathy for drug discovery. Cell Reports Medicine 2023, 4: 100976. PMID: 36921598, PMCID: PMC10040415, DOI: 10.1016/j.xcrm.2023.100976.Peer-Reviewed Original ResearchConceptsRestrictive cardiomyopathyElevated ventricular filling pressuresVentricular filling pressurePrecision medicine approachVariety of cardiomyopathiesPluripotent stem cell-derived cardiomyocytesStem cell-derived cardiomyocytesDiastolic relaxationCardiomyocyte relaxationFilamin CMyocardial relaxationCell-derived cardiomyocytesFilling pressurePotential therapyRelaxation velocityMyocardial stiffnessCalcium kineticsMedicine approachCardiomyopathyTranslational potentialIsogenic control linesCardiac tissuePassive tensionScreening identifiesTissue model
2022
RASGRF1 Fusions Activate Oncogenic RAS Signaling and Confer Sensitivity to MEK Inhibition.
Hunihan L, Zhao D, Lazowski H, Li M, Qian Y, Abriola L, Surovtseva YV, Muthusamy V, Tanoue LT, Rothberg BE, Schalper KA, Herbst RS, Wilson FH. RASGRF1 Fusions Activate Oncogenic RAS Signaling and Confer Sensitivity to MEK Inhibition. Clinical Cancer Research 2022, 28: 3091-3103. PMID: 35247929, PMCID: PMC9288503, DOI: 10.1158/1078-0432.ccr-21-4291.Peer-Reviewed Original ResearchConceptsLung adenocarcinomaSmoking historyPack-year smoking historyMinimal smoking historySubset of patientsPancreatic ductal adenocarcinoma cell linesPotential treatment strategyTight junction protein occludinJunction protein occludinWhole-exome sequencingAdenocarcinoma cell lineAdvanced malignanciesCancer Genome AtlasRaf-MEKAdvanced tumorsMultiple malignanciesTreatment strategiesKRAS mutationsTherapeutic strategiesTherapeutic targetOncogenic RAS SignalingRelated commentaryOncogenic driversMEK inhibitionOncogenic alterations
2021
Phosphorylated WNK kinase networks in recoded bacteria recapitulate physiological function
Schiapparelli P, Pirman NL, Mohler K, Miranda-Herrera PA, Zarco N, Kilic O, Miller C, Shah SR, Rogulina S, Hungerford W, Abriola L, Hoyer D, Turk BE, Guerrero-Cázares H, Isaacs FJ, Quiñones-Hinojosa A, Levchenko A, Rinehart J. Phosphorylated WNK kinase networks in recoded bacteria recapitulate physiological function. Cell Reports 2021, 36: 109416. PMID: 34289367, PMCID: PMC8379681, DOI: 10.1016/j.celrep.2021.109416.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell Line, TumorCell MovementCell ProliferationEscherichia coliFemaleGlioblastomaHEK293 CellsHumansMaleMice, NudeMiddle AgedPhosphorylationPhosphoserineProtein Serine-Threonine KinasesRecombinant ProteinsSignal TransductionSmall Molecule LibrariesSubstrate SpecificityWNK Lysine-Deficient Protein Kinase 1ConceptsKinase networkAuthentic post-translational modificationsGenetic code expansionPost-translational modificationsProduction of proteinsSmall molecule kinase inhibitorsKinase inhibitorsGenetic codePhosphorylated proteinsCode expansionKinase proteinWNK kinasesPhysiological functionsWNK4 kinaseBiochemical propertiesGlioblastoma cellsKinaseBacterial strainsProteinDistinct sitesPhosphoserineSPAKBacteriaCellular systemsCellsIncreased numbers of nucleoli in a genome-wide RNAi screen reveal proteins that link the cell cycle to RNA polymerase I transcription
Ogawa LM, Buhagiar AF, Abriola L, Leland BA, Surovtseva YV, Baserga SJ. Increased numbers of nucleoli in a genome-wide RNAi screen reveal proteins that link the cell cycle to RNA polymerase I transcription. Molecular Biology Of The Cell 2021, 32: 956-973. PMID: 33689394, PMCID: PMC8108525, DOI: 10.1091/mbc.e20-10-0670.Peer-Reviewed Original ResearchConceptsRNA polymerase INumber of nucleoliRibosome biogenesisNucleolar organizer regionsPolymerase ICell cycleRNA polymerase I transcriptionPolymerase I transcriptionCell cycle regulationHigh-throughput quantitative imagingHuman diploid genomeIdentification of proteinsEukaryotic cellsG2/M phaseDiploid genomeNuclear condensatesRibosomal DNACycle regulationHuman breast epithelial cell lineBreast epithelial cell lineI transcriptionNovel regulatorEpithelial cell lineCycle progressionFunctional analysis
2020
An allosteric site on MKP5 reveals a strategy for small-molecule inhibition
Gannam Z, Min K, Shillingford SR, Zhang L, Herrington J, Abriola L, Gareiss PC, Pantouris G, Tzouvelekis A, Kaminski N, Zhang X, Yu J, Jamali H, Ellman JA, Lolis E, Anderson KS, Bennett AM. An allosteric site on MKP5 reveals a strategy for small-molecule inhibition. Science Signaling 2020, 13 PMID: 32843541, PMCID: PMC7569488, DOI: 10.1126/scisignal.aba3043.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric SiteAmino Acid SequenceAnimalsCell DifferentiationCell LineDual-Specificity PhosphatasesEnzyme InhibitorsFemaleHigh-Throughput Screening AssaysHumansKineticsMiceMice, KnockoutMitogen-Activated Protein Kinase PhosphatasesMyoblastsProtein BindingSequence Homology, Amino AcidSignal TransductionSmall Molecule LibrariesConceptsDystrophic muscle diseaseMitogen-activated protein kinaseMuscle diseaseTGF-β1Promising therapeutic targetP38 mitogen-activated protein kinaseTherapeutic strategiesTherapeutic targetSmall molecule inhibitionSmad2 phosphorylationDiseasePotential targetSmall-molecule screenInhibitorsTreatmentInhibition
2014
Identification of Inhibitors of Inositol 5‑Phosphatases through Multiple Screening Strategies
Pirruccello M, Nandez R, Idevall-Hagren O, Alcazar-Roman A, Abriola L, Berwick SA, Lucast L, Morel D, De Camilli P. Identification of Inhibitors of Inositol 5‑Phosphatases through Multiple Screening Strategies. ACS Chemical Biology 2014, 9: 1359-1368. PMID: 24742366, PMCID: PMC4076014, DOI: 10.1021/cb500161z.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedDermisElectrophoretic Mobility Shift AssayEnzyme InhibitorsFibroblastsFluorescence PolarizationHigh-Throughput Screening AssaysHumansInositol Polyphosphate 5-PhosphatasesMolecular StructurePhosphatidylinositol PhosphatesPhosphoric Monoester HydrolasesRosaniline DyesSignal TransductionSmall Molecule LibrariesThiadiazolesTriazolesConceptsPhosphoinositide-metabolizing enzymesGrowth factor signalingSmall molecule modulatorsIdentification of inhibitorsFamily of enzymesMembrane traffickingActin nucleationCytoskeletal dynamicsCell cortexPhosphoinositide levelsCatalytic domainFactor signalingMolecule modulatorsHigh-throughput screeningLiving cellsSpecific inhibitorActivity assaysMembrane phospholipidsDirect interactionCell proliferationChemical scaffoldsPowerful research toolPotential therapeutic applicationsOCRLPhosphoinositide