2023
Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection
Wei J, Patil A, Collings C, Alfajaro M, Liang Y, Cai W, Strine M, Filler R, DeWeirdt P, Hanna R, Menasche B, Ökten A, Peña-Hernández M, Klein J, McNamara A, Rosales R, McGovern B, Luis Rodriguez M, García-Sastre A, White K, Qin Y, Doench J, Yan Q, Iwasaki A, Zwaka T, Qi J, Kadoch C, Wilen C. Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection. Nature Genetics 2023, 55: 471-483. PMID: 36894709, PMCID: PMC10011139, DOI: 10.1038/s41588-023-01307-z.Peer-Reviewed Original ResearchConceptsMSWI/SNF complexesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionHost-directed therapeutic targetSyndrome coronavirus 2 infectionSARS-CoV-2 infectionSWItch/Sucrose Non-Fermentable (SWI/SNF) chromatinSARS-CoV-2 susceptibilityNon-fermentable (SWI/SNF) chromatinCoronavirus 2 infectionEnzyme 2 (ACE2) expressionSARS-CoV-2 variantsHuman cell typesPrimary human cell typesAirway epithelial cellsDrug-resistant variantsNew drug targetsChromatin accessibilitySNF complexACE2 locusACE2 expressionFactor complexHost determinantsTherapeutic targetConfer resistance
2022
Diversification of aminoacyl-tRNA synthetase activities via genomic duplication
Krahn N, Söll D, Vargas-Rodriguez O. Diversification of aminoacyl-tRNA synthetase activities via genomic duplication. Frontiers In Physiology 2022, 13: 983245. PMID: 36060688, PMCID: PMC9437257, DOI: 10.3389/fphys.2022.983245.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsGenomic duplicationSynthetase familyRecent bioinformatic analysisAminoacyl-tRNA synthetase familySynthetic biology applicationsDomains of lifeNew drug targetsAminoacyl-tRNA synthetase activityGene duplicationPhylogenetic diversityEvolutionary eventsGenetic codeBioinformatics analysisImportant bioactive moleculesAdaptive advantageBiological functionsBiological processesBiology applicationsDrug targetsDuplicationAaRSsCatalytic siteSynthetase activityProteinBioactive moleculesFurther delineation of familial polycystic ovary syndrome (PCOS) via whole‐exome sequencing: PCOS‐related rare FBN3 and FN1 gene variants are identified
Karakaya C, Çil AP, Bilguvar K, Çakir T, Karalok MH, Karabacak RO, Caglayan AO. Further delineation of familial polycystic ovary syndrome (PCOS) via whole‐exome sequencing: PCOS‐related rare FBN3 and FN1 gene variants are identified. Journal Of Obstetrics And Gynaecology Research 2022, 48: 1202-1211. PMID: 35141985, PMCID: PMC9050819, DOI: 10.1111/jog.15187.Peer-Reviewed Original ResearchConceptsPolycystic ovary syndromeWhole-exome sequencingFurther functional studiesMissense variantsNew drug targetsGerm-line DNAWhole-exome sequencing dataThree-dimensional structurePolycystic ovary syndrome patientsFunctional predictionChemogenomic analysisCandidate proteinsSequencing dataBiological pathwaysDrug targetsFunctional studiesCandidate variantsSequencingPCOS familiesRotterdam criteriaOvary syndromeFBN3Syndrome patientsPathwayPCOS probands
2021
Abnormal levels of mitochondrial proteins in plasma neuronal extracellular vesicles in major depressive disorder
Goetzl EJ, Wolkowitz OM, Srihari VH, Reus VI, Goetzl L, Kapogiannis D, Heninger GR, Mellon SH. Abnormal levels of mitochondrial proteins in plasma neuronal extracellular vesicles in major depressive disorder. Molecular Psychiatry 2021, 26: 7355-7362. PMID: 34471251, PMCID: PMC8872999, DOI: 10.1038/s41380-021-01268-x.Peer-Reviewed Original ResearchConceptsNeuron-derived extracellular vesiclesMitochondrial proteinsCyclophilin DMitofusin 2Extracellular vesiclesFunctional mitochondrial proteinsElectron transport complexes INuclear respiratory factorOpen-reading frameNeuronal extracellular vesiclesNew drug targetsΓ coactivator 1αPenultimate enzymeTranscription factorsMajor depressive disorderLeucine zipperMyosin VIGene responsesMitochondrial biogenesisPotential biomarker proteinsProtein componentsSelective serotonin reuptake inhibitorsPPAR-γ coactivator 1αComplex IDrug targets
2020
Preclinical insights into therapeutic targeting of KCC2 for disorders of neuronal hyperexcitability
Duy PQ, He M, He Z, Kahle KT. Preclinical insights into therapeutic targeting of KCC2 for disorders of neuronal hyperexcitability. Expert Opinion On Therapeutic Targets 2020, 24: 629-637. PMID: 32336175, PMCID: PMC8104019, DOI: 10.1080/14728222.2020.1762174.Peer-Reviewed Original ResearchConceptsNeuronal hyperexcitabilityKCC2 functionSynaptic inhibitionKCC2 activityPreclinical insightsRole of KCC2Treatment of epilepsyCommon neurological disorderNovel therapeutic strategiesPotential adverse effectsDrug targetsKCC2 dysfunctionSeizure reductionUnprovoked seizuresIntractable epilepsySeizure activityEpilepsy therapyCotransporter KCC2Clinical urgencyPreclinical proofTherapeutic benefitTherapeutic strategiesNew drug targetsTherapeutic targetingKCC2
2018
Druggable negative allosteric site of P2X3 receptors
Wang J, Wang Y, Cui W, Huang Y, Yang Y, Liu Y, Zhao W, Cheng X, Sun W, Cao P, Zhu M, Wang R, Hattori M, Yu Y. Druggable negative allosteric site of P2X3 receptors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: 4939-4944. PMID: 29674445, PMCID: PMC5948998, DOI: 10.1073/pnas.1800907115.Peer-Reviewed Original ResearchConceptsAllosteric siteNegative allosteric siteDruggable allosteric sitesG protein-coupled receptorsAllosteric modulationLeft flipperProtein-coupled receptorsNew drug targetsDorsal fin domainLB domainsClinical trialsP2X receptorsAllosteric changesAllosteric inhibitorsChannel mutantsDrug targetsPhase II clinical trialFunctional studiesFin domainRefractory chronic coughIdiopathic pulmonary fibrosisIon channelsLower bodyX-ray crystallographyNegative allosteric modulation
2014
Troponin I-Interacting Protein Kinase
Lal H, Ahmad F, Parikh S, Force T. Troponin I-Interacting Protein Kinase. Circulation Journal 2014, 78: 1514. PMID: 24899531, PMCID: PMC4151348, DOI: 10.1253/circj.cj-14-0543.Peer-Reviewed Original ResearchConceptsIR injuryMyocardial infarctionCardiomyocyte deathNew drug targetsNovel genetic animal modelsEffective myocardial reperfusionAcute coronary syndromeIschemia-reperfusion injuryPercutaneous coronary interventionCoronary artery diseaseCause of deathProfound oxidative stressPromising new drug targetGenetic animal modelsCardiac troponin ITNNI3KDrug targetsCoronary syndromeCoronary interventionArtery diseaseMyocardial reperfusionReperfusion injuryCardiac dysfunctionIschemic injuryInfarct size
2012
Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation
Tautz L, Sergienko E, Xu J, Liu W, Dahl R, Critton D, Su Y, Brown B, Chan X, Yang L, Bobkova E, Vasile S, Yuan H, Rascon J, Colayco S, Sidique S, Cosford N, Chung T, Mustelin T, Page R, Lombroso P. Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation. The FASEB Journal 2012, 26: 766.12-766.12. DOI: 10.1096/fasebj.26.1_supplement.766.12.Peer-Reviewed Original ResearchHematopoietic protein tyrosine phosphataseP38 activationProtein tyrosine phosphataseUnique amino acid residuesAmino acid residuesNew drug targetsCell cycle arrestMAP kinases ERK1/2Activation of ERK1/2Tyrosine phosphataseHePTPMutagenesis experimentsMAP kinaseKinases ERK1/2Acid residuesCatalytic pocketDrug targetsTransient activationCycle arrestT-cell acute lymphoblastic leukemiaERK1/2Prolonged activationHuman T cellsPharmacological inhibitionCancer cellsPathogenesis in tuberculosis: transcriptomic approaches to unraveling virulence mechanisms and finding new drug targets
Mukhopadhyay S, Nair S, Ghosh S. Pathogenesis in tuberculosis: transcriptomic approaches to unraveling virulence mechanisms and finding new drug targets. FEMS Microbiology Reviews 2012, 36: 463-485. PMID: 22092372, DOI: 10.1111/j.1574-6976.2011.00302.x.Peer-Reviewed Original ResearchConceptsMajor health problemHost immune responseEmergence of strainsDrug targetsDendritic cellsEffective drug targetsInhibition of apoptosisImmune responseNew drug targetsHealth problemsLipid metabolismMultiple drugsTuberculosisComplex etiologyMycobacterium tuberculosisIntracellular life styleTranscriptome signaturesVirulence mechanismsGenome-wide expression profilingDrugsAntibiotic drugsExpression profilingProtein secretionLife stylePoor understanding
2011
Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation
Sergienko E, Xu J, Liu WH, Dahl R, Critton DA, Su Y, Brown BT, Chan X, Yang L, Bobkova EV, Vasile S, Yuan H, Rascon J, Colayco S, Sidique S, Cosford ND, Chung TD, Mustelin T, Page R, Lombroso PJ, Tautz L. Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation. ACS Chemical Biology 2011, 7: 367-377. PMID: 22070201, PMCID: PMC3288537, DOI: 10.1021/cb2004274.Peer-Reviewed Original ResearchConceptsHematopoietic protein tyrosine phosphataseP38 activationMitogen-activated protein kinases ERK1/2Protein tyrosine phosphataseUnique amino acid residuesSmall molecule modulatorsProtein kinases ERK1/2Amino acid residuesRegulation of MAPKNew drug targetsCell cycle arrestTyrosine phosphataseHePTPMutagenesis experimentsKinases ERK1/2Acid residuesCatalytic pocketCell senescenceDrug targetsTransient activationCycle arrestT-cell acute lymphoblastic leukemiaHematopoietic cellsERK1/2Prolonged activation
2010
Glycobiology of the Leishmania parasite and emerging targets for antileishmanial drug discovery
Chandra S, Ruhela D, Deb A, Vishwakarma R. Glycobiology of the Leishmania parasite and emerging targets for antileishmanial drug discovery. Expert Opinion On Therapeutic Targets 2010, 14: 739-757. PMID: 20536412, DOI: 10.1517/14728222.2010.495125.Peer-Reviewed Original ResearchConceptsDrug targetsUpcoming drug targetsNew drug targetsPurine salvage pathwayDrug discoveryPromising drug targetSalvage pathwayNovel pathwayRelated biochemistryAnchored glycoconjugatesLeishmania speciesPathwayDrug resistanceLeishmania parasitesAntileishmanial drug discoveryDiscoveryGlycosomesTargetGenomicsGlycosylphosphatidylinositolGlycobiologySpeciesBioinformaticsParasitic diseasesProtozoa
2006
Chromosome-Wide Analysis of Gene Function by RNA Interference in the African Trypanosome
Subramaniam C, Veazey P, Redmond S, Hayes-Sinclair J, Chambers E, Carrington M, Gull K, Matthews K, Horn D, Field M. Chromosome-Wide Analysis of Gene Function by RNA Interference in the African Trypanosome. MSphere 2006, 5: 1539-1549. PMID: 16963636, PMCID: PMC1563588, DOI: 10.1128/ec.00141-06.Peer-Reviewed Original ResearchConceptsOpen reading frameRNA interferenceGene functionChromosome IT. bruceiDrug targetsChromosome-wide analysisBloodstream form parasitesCell cycle progressionPotential drug targetsNew drug targetsTrypanosome genomeGrowth defectOrder KinetoplastidaGenome sequenceAffected cell growthI geneParasite biologyReading frameGene productsTrypanosoma bruceiBasic biologyParasitic organismsAfrican trypanosomesCycle progression
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply