2025
VAC14 oligomerization is essential for the function of the FAB1/PIKfyve-VAC14-FIG4 complex.
Zhang L, Uygun T, Hahn H, Liu Y, Rivero-Ríos P, Li D, Navratna V, Bristow E, Luo G, Kovarzin A, Bo Y, Gadde S, Côté M, Ko D, Mosalaganti S, Reinisch K, Weisman L. VAC14 oligomerization is essential for the function of the FAB1/PIKfyve-VAC14-FIG4 complex. Molecular Biology Of The Cell 2025, 36: ar78. PMID: 40305106, DOI: 10.1091/mbc.e24-11-0490.Peer-Reviewed Original ResearchMeSH KeywordsCryoelectron MicroscopyFlavoproteinsHexosyltransferasesHumansIntracellular Signaling Peptides and ProteinsMembrane ProteinsMutationPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPhosphoric Monoester HydrolasesPhosphotransferases (Alcohol Group Acceptor)Protein BindingProtein MultimerizationSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsVesicular Transport ProteinsConceptsPatient mutationsFluorescence-detection size-exclusion chromatographyPI(3,5)P<sub>2</sub>Phosphatidylinositol 3,5-bisphosphatePull-down assaysMedium-resolution structureYeast mutationsPediatric neurodegenerative diseaseVac14Signaling lipidsCell lysatesMutationsOligomerizationNeurodegenerative diseasesElectron microscopy mappingKnockoutFab1/PIKfyveYeastEndosomesFIG4PIKfyveLysatesColocalizationComplexRegulationCCL17 Influences Borrelia burgdorferi Infection in the Heart
Tang X, Yu Q, Cui Y, Hart T, Rivas-Giorgi F, Calloway K, Mohapatra A, Fikrig E. CCL17 Influences Borrelia burgdorferi Infection in the Heart. The Journal Of Infectious Diseases 2025, jiaf011. PMID: 39777514, DOI: 10.1093/infdis/jiaf011.Peer-Reviewed Original ResearchSerum levels of proinflammatory cytokinesLevels of proinflammatory cytokinesVector-Borne PathogensB. burgdorferiReduce pathogen loadImmune alterationsMacrophage infiltrationProinflammatory cytokinesCCL17B. burgdorferi infectionIxodes ticksPathogen loadControl animalsChemokinesBorrelia burgdorferiInfectious diseasesInfectionDiverse illnessesKnockoutLyme diseaseDisease
2024
Mice deficient in TWIK-1 are more susceptible to kainic acid-induced seizures
Kim A, Bae Y, Gadhe C, Jung H, Yang E, Kim H, Lee J, Shim C, Sung Y, Noh J, Kim E, Kang D, Pae A, Hwang E, Park J. Mice deficient in TWIK-1 are more susceptible to kainic acid-induced seizures. IScience 2024, 28: 111587. PMID: 39811670, PMCID: PMC11732521, DOI: 10.1016/j.isci.2024.111587.Peer-Reviewed Original ResearchAnopheles gambiae lacking AgTRIO probe inefficiently on a mammalian host
Chuang Y, Dong Y, Stone H, Abouneameh S, Tang X, Raduwan H, Dimopoulos G, Fikrig E. Anopheles gambiae lacking AgTRIO probe inefficiently on a mammalian host. Cell Reports 2024, 43: 114600. PMID: 39126653, PMCID: PMC11407849, DOI: 10.1016/j.celrep.2024.114600.Peer-Reviewed Original ResearchVertebrate hostsAnopheles gambiaePlasmodium sporozoitesCRISPR-Cas9-mediated genome editingPlasmodium transmissionTransmit malariaMosquito probingMosquito salivaTransmit PlasmodiumBlood resourcesMalariaRepetitive probesBloodPlasmodiumMammalian hostsAbility of mosquitoesBlood mealGenome editingA. gambiaeKnockoutVertebratesGambiaHostMealSalivaNADPH oxidase in B cells and macrophages protects against murine lupus by regulation of TLR7
Gordon R, Cosgrove H, Marinov A, Gingras S, Tilstra J, Campbell A, Bastacky S, Kashgarian M, Perl A, Nickerson K, Shlomchik M. NADPH oxidase in B cells and macrophages protects against murine lupus by regulation of TLR7. JCI Insight 2024, 9: e178563. PMID: 39042716, PMCID: PMC11343599, DOI: 10.1172/jci.insight.178563.Peer-Reviewed Original ResearchSystemic lupus erythematosusB cellsRegulation of TLR7Cell lineagesNADPH oxidaseHematopoietic cell lineagesNF-kB signalingSLE pathologyNOX2 deficiencyMyeloid compartmentMurine lupusLupus nephritisLupus erythematosusTLR7 signalingGlobal deletionInterstitial nephritisImmunomodulatory effectsGlobal knockoutConditional knockoutCYBBNOX2NephritisKnockoutTLR7Chimera approach
2023
Manipulating mitochondrial electron flow enhances tumor immunogenicity
Mangalhara K, Varanasi S, Johnson M, Burns M, Rojas G, Esparza Moltó P, Sainz A, Tadepalle N, Abbott K, Mendiratta G, Chen D, Farsakoglu Y, Kunchok T, Hoffmann F, Parisi B, Rincon M, Vander Heiden M, Bosenberg M, Hargreaves D, Kaech S, Shadel G. Manipulating mitochondrial electron flow enhances tumor immunogenicity. Science 2023, 381: 1316-1323. PMID: 37733872, PMCID: PMC11034774, DOI: 10.1126/science.abq1053.Peer-Reviewed Original ResearchConceptsElectron transport chainMethylation-controlled J proteinMitochondrial electron transport chainElectron flowMitochondrial electron flowJ-proteinsEpigenetic activationTransport chainMitochondrial respirationTumor growthPresentation genesElectron entryNoncancer cellsMelanoma tumor growthCommon mechanismTherapeutic potentialGenesRelative contributionProteinGrowthKnockoutAntigen presentationRespirationT cell-mediated killingExpression
2021
Intracellular C3 prevents hepatic steatosis by promoting autophagy and very‐low‐density lipoprotein secretion
Li Y, Sha Y, Wang H, He L, Li L, Wen S, Sheng L, Hu W, Zhou H. Intracellular C3 prevents hepatic steatosis by promoting autophagy and very‐low‐density lipoprotein secretion. The FASEB Journal 2021, 35: e22037. PMID: 34762761, DOI: 10.1096/fj.202100856r.Peer-Reviewed Original ResearchConceptsVery-low-density lipoprotein secretionVery-low-density lipoproteinProtein disulfide isomeraseExpression of protein disulfide isomeraseMicrosomal TG transfer proteinPathogen recognitionHepatic lipid accumulationDisulfide isomeraseEndoplasmic reticulumIntracellular functionsAutophagy-relatedExtracellular milieuDisrupt interactionsVLDL secretionTransfer proteinLipoprotein secretionLipid accumulationIntracellular C3C3<sup>-/-</sup> miceComplement component C3C3 knockoutHepatic steatosisConvergence pointWild type miceKnockoutTET1-mediated DNA hydroxymethylation regulates adult remyelination in mice
Moyon S, Frawley R, Marechal D, Huang D, Marshall-Phelps KLH, Kegel L, Bøstrand SMK, Sadowski B, Jiang YH, Lyons DA, Möbius W, Casaccia P. TET1-mediated DNA hydroxymethylation regulates adult remyelination in mice. Nature Communications 2021, 12: 3359. PMID: 34099715, PMCID: PMC8185117, DOI: 10.1038/s41467-021-23735-3.Peer-Reviewed Original ResearchConceptsDNA hydroxymethylationSolute carrier gene familyNeuro-glial communicationZebrafish mutantsGene familyTranscriptomic analysisMyelin interfaceTen-ElevenAdult central nervous systemCentral nervous systemTET1Overexpressing cellsAdult remyelinationExpression levelsMutantsHydroxymethylationGenesNervous systemRepairMyelin repairTransportersKnockoutMiceRegulationAged miceNoncanonical open reading frames encode functional proteins essential for cancer cell survival
Prensner J, Enache O, Luria V, Krug K, Clauser K, Dempster J, Karger A, Wang L, Stumbraite K, Wang V, Botta G, Lyons N, Goodale A, Kalani Z, Fritchman B, Brown A, Alan D, Green T, Yang X, Jaffe J, Roth J, Piccioni F, Kirschner M, Ji Z, Root D, Golub T. Noncanonical open reading frames encode functional proteins essential for cancer cell survival. Nature Biotechnology 2021, 39: 697-704. PMID: 33510483, PMCID: PMC8195866, DOI: 10.1038/s41587-020-00806-2.Peer-Reviewed Original ResearchConceptsCancer cell linesOpen reading framePotential therapeutic targetCell linesGrowth inhibitory effectsCancer cell survivalInduced gene expression changesBreast cancerTherapeutic targetHuman cancer cell linesReading frameProtein expressionActive proteinProtein 1Gene expression changesCell survivalBiological effectsExpression changesViability defectsHuman genomeGenomic analysisCodon mutagenesisEctopic expressionFunctional proteinsKnockoutA simple and effective F0 knockout method for rapid screening of behaviour and other complex phenotypes
Kroll F, Powell GT, Ghosh M, Gestri G, Antinucci P, Hearn TJ, Tunbak H, Lim S, Dennis HW, Fernandez JM, Whitmore D, Dreosti E, Wilson SW, Hoffman EJ, Rihel J. A simple and effective F0 knockout method for rapid screening of behaviour and other complex phenotypes. ELife 2021, 10: e59683. PMID: 33416493, PMCID: PMC7793621, DOI: 10.7554/elife.59683.Peer-Reviewed Original ResearchConceptsKnockout methodComplex mutant phenotypesLarge genetic screenRapid genetic screeningGenetic screenMutant phenotypeEffective CRISPRBiallelic knockoutMolecular rhythmsHuman genesInjected embryosCircadian clockLarval zebrafishBehavioral phenotypesMultiple genesComplex phenotypesCurrent CRISPRTriple knockoutAttractive modelGenesGenetic contributionZebrafishPhenotypeKnockoutCRISPR
2020
Phosphoinositide 3′-Kinase γ Facilitates Polyomavirus Infection
Clark P, Gee GV, Albright BS, Assetta B, Han Y, Atwood WJ, DiMaio D. Phosphoinositide 3′-Kinase γ Facilitates Polyomavirus Infection. Viruses 2020, 12: 1190. PMID: 33092168, PMCID: PMC7589550, DOI: 10.3390/v12101190.Peer-Reviewed Original ResearchConceptsCRISPR/Cas9-mediated knockoutGenetic knockdown approachesCas9-mediated knockoutDNA tumor virusesProgressive multifocal leukoencephalopathyInfection defectPolyomavirus infectionCellular proteinsKnockdown approachSVG-A cellsPolyomavirus entryMolecular eventsVirus internalizationTumor virusPI3Kγ pathwayPIK3R5PI3KγGlial cellsKnockoutMultifocal leukoencephalopathyImmunosuppressed peopleCellsHuman polyomavirusesJC polyomavirusPolyomavirus
2019
High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation
Abeler-Dörner L, Laing A, Lorenc A, Ushakov D, Clare S, Speak A, Duque-Correa M, White J, Ramirez-Solis R, Saran N, Bull K, Morón B, Iwasaki J, Barton P, Caetano S, Hng K, Cambridge E, Forman S, Crockford T, Griffiths M, Kane L, Harcourt K, Brandt C, Notley G, Babalola K, Warren J, Mason J, Meeniga A, Karp N, Melvin D, Cawthorne E, Weinrick B, Rahim A, Drissler S, Meskas J, Yue A, Lux M, Song-Zhao G, Chan A, Ballesteros Reviriego C, Abeler J, Wilson H, Przemska-Kosicka A, Edmans M, Strevens N, Pasztorek M, Meehan T, Powrie F, Brinkman R, Dougan G, Jacobs W, Lloyd C, Cornall R, Maloy K, Grencis R, Griffiths G, Adams D, Hayday A. High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation. Nature Immunology 2019, 21: 86-100. PMID: 31844327, PMCID: PMC7338221, DOI: 10.1038/s41590-019-0549-0.Peer-Reviewed Original ResearchConceptsHigh-throughput genetic screensImmune variationHigh-throughput phenotypingMouse gene knockoutsAssociated with immunocompetenceGenetic screeningLoss of functionContribution of geneticsPhysiological traitsGenetic resourcesGene knockoutIndividual immune parametersImmune parametersCorrelation networkPhenotypeImmunological structureTolerance to lossGenesHitsGeneticsStructural underpinningsTraitsKnockoutStructural perspectiveVariationApical-Basal Polarity Signaling Components, Lgl1 and aPKCs, Control Glutamatergic Synapse Number and Function
Scott J, Thakar S, Mao Y, Qin H, Hejran H, Lee SY, Yu T, Klezovitch O, Cheng H, Mu Y, Ghosh S, Vasioukhin V, Zou Y. Apical-Basal Polarity Signaling Components, Lgl1 and aPKCs, Control Glutamatergic Synapse Number and Function. IScience 2019, 20: 25-41. PMID: 31546104, PMCID: PMC6817635, DOI: 10.1016/j.isci.2019.09.005.Peer-Reviewed Original ResearchAtypical protein kinase CsApical-basal polarity proteinsPolarity proteinsPlanar cell polarity proteinsCell polarity proteinsConditional knockoutSynapse formationProtein kinase CsSmith-Magenis syndromeGlutamatergic synapse developmentSynapse numberKnockout embryosSignaling ComponentsSynapse developmentNormal synapse formationLgl1ProteinPostsynaptic densityCultured cortical neuronsKnockoutSynaptosome fractionVangl2EmbryosImpaired plasticityCortical neuronsGSAP modulates γ-secretase specificity by inducing conformational change in PS1
Wong E, Liao G, Chang J, Xu P, Li Y, Greengard P. GSAP modulates γ-secretase specificity by inducing conformational change in PS1. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 6385-6390. PMID: 30850537, PMCID: PMC6442608, DOI: 10.1073/pnas.1820160116.Peer-Reviewed Original Research
2017
Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration
Patterson M, Barske L, Van Handel B, Rau CD, Gan P, Sharma A, Parikh S, Denholtz M, Huang Y, Yamaguchi Y, Shen H, Allayee H, Crump JG, Force TI, Lien CL, Makita T, Lusis AJ, Kumar SR, Sucov HM. Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration. Nature Genetics 2017, 49: 1346-1353. PMID: 28783163, PMCID: PMC5736145, DOI: 10.1038/ng.3929.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, Genetically ModifiedCells, CulturedDiploidyGene Expression ProfilingHeartImmunoblottingIn Situ Hybridization, FluorescenceMice, Inbred C57BLMice, KnockoutMice, TransgenicMicroscopy, ConfocalMyocardiumMyocytes, CardiacProtein KinasesProtein Serine-Threonine KinasesRegenerationZebrafish
2016
The Dual NOD1/NOD2 Agonism of Muropeptides Containing a Meso-Diaminopimelic Acid Residue
Dagil Y, Arbatsky N, Alkhazova B, L’vov V, Mazurov D, Pashenkov M. The Dual NOD1/NOD2 Agonism of Muropeptides Containing a Meso-Diaminopimelic Acid Residue. PLOS ONE 2016, 11: e0160784. PMID: 27513337, PMCID: PMC4981496, DOI: 10.1371/journal.pone.0160784.Peer-Reviewed Original ResearchConceptsMeso-DAPNucleotide-Binding Oligomerization DomainMeso-diaminopimelic acidGram-negative peptidoglycanFragments of peptidoglycanHEK293T cellsCRISPR/Cas9-mediated knockoutGram-negative bacteriaInnate immune responseActivating nucleotide-binding oligomerization domainOverexpression systemOligomerization domainMuropeptidesActivate NOD1Non-terminal positionNOD1Cell typesNOD2 geneNOD2PeptidoglycanResiduesPeptide chainKnockoutBiological activityMicromolar concentrations
2013
Chronic treatment with LY341495 decreases 5-HT2A receptor binding and hallucinogenic effects of LSD in mice
Moreno JL, Holloway T, Rayannavar V, Sealfon SC, González-Maeso J. Chronic treatment with LY341495 decreases 5-HT2A receptor binding and hallucinogenic effects of LSD in mice. Neuroscience Letters 2013, 536: 69-73. PMID: 23333599, PMCID: PMC3578056, DOI: 10.1016/j.neulet.2012.12.053.Peer-Reviewed Original ResearchMeSH KeywordsAmino AcidsAnimalsDrug AntagonismEarly Growth Response Protein 1Early Growth Response Protein 2HallucinogensLysergic Acid DiethylamideMaleMiceMice, KnockoutProto-Oncogene Proteins c-fosRadioligand AssayReceptor, Serotonin, 5-HT2AReceptors, Metabotropic GlutamateSomatosensory CortexStereotyped BehaviorXanthenesConceptsLysergic acid diethylamideChronic treatmentHallucinogenic drugsHallucinogenic effectsHead-twitch behaviorHallucinogenic 5MGlu2 receptorLast injectionSomatosensory cortexLY341495Serotonin 5Receptor bindingAcid diethylamideC-fosReceptor ligandsMiceDrugsTreatmentEgr-2Egr-1ReceptorsBehavioral responsesKnockoutHigh affinityMetabotropicThe contribution of TWIK-1 channels to astrocyte K+ current is limited by retention in intracellular compartments
Wang W, Putra A, Schools GP, Ma B, Chen H, Kaczmarek LK, Barhanin J, Lesage F, Zhou M. The contribution of TWIK-1 channels to astrocyte K+ current is limited by retention in intracellular compartments. Frontiers In Cellular Neuroscience 2013, 7: 246. PMID: 24368895, PMCID: PMC3856854, DOI: 10.3389/fncel.2013.00246.Peer-Reviewed Original ResearchTWIK-1 channelsTWIK-1Plasma membraneIntracellular compartmentsMature hippocampal astrocytesTwo-pore domainWild-type animalsFractionation experimentsTwo-poreKnockout miceCytoplasmic fractionExpression of Kir4.1Compartment fractionsType animalsPhysiological conditionsTREK-1Whole-cell currentsLow-level presenceKnockoutLinear current-voltage relationshipCompartmentsMembraneMild effect
2008
The evolution of courtship behaviors through the origination of a new gene in Drosophila
Dai H, Chen Y, Chen S, Mao Q, Kennedy D, Landback P, Eyre-Walker A, Du W, Long M. The evolution of courtship behaviors through the origination of a new gene in Drosophila. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 7478-7483. PMID: 18508971, PMCID: PMC2396706, DOI: 10.1073/pnas.0800693105.Peer-Reviewed Original ResearchConceptsMale-male courtshipD. melanogasterChimeric geneCourtship behaviorNew genesRelated Drosophila speciesNew chimeric genesDrosophila speciesAdaptive evolutionMutant phenotypeDrosophila melanogasterAncestral conditionUnrelated genesPhenotypic effectsMelanogasterNovel phenotypesCombination of sequenceMating behaviorChimeric structureGenesCourtshipSpeciesPhenotypeDrosophilaKnockoutA Critical Role for Vascular Smooth Muscle in Acute Glucocorticoid-Induced Hypertension
Goodwin JE, Zhang J, Geller DS. A Critical Role for Vascular Smooth Muscle in Acute Glucocorticoid-Induced Hypertension. Journal Of The American Society Of Nephrology 2008, 19: 1291-1299. PMID: 18434569, PMCID: PMC2440298, DOI: 10.1681/asn.2007080911.Peer-Reviewed Original ResearchConceptsVascular smooth muscleAcute hypertensive responseHypertensive responseKO miceSmooth muscleGC receptorChronic hypertensive responseGlucocorticoid-Induced HypertensionNormal circadian variationBaseline BPTissue-specific knockoutMineralocorticoid receptorMouse modelHypertensionExcess reabsorptionCircadian variationCritical roleMiceReceptorsPromiscuous activationMuscleVivoKnockoutResponseGlucocorticoids
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