2025
The ABCs of psychedelics: a preclinical roadmap for drug discovery
Kwan A, Mantsch J, McCorvy J. The ABCs of psychedelics: a preclinical roadmap for drug discovery. Trends In Pharmacological Sciences 2025 PMID: 40877079, PMCID: PMC12404667, DOI: 10.1016/j.tips.2025.07.017.Peer-Reviewed Original ResearchActivity-dependent gene expressionSerotonin 2APsychiatric disordersBehavioral phenotypesTherapeutic efficacyNeural remodelingPsychedelicsCellular plasticityReceptor selectivityDrug developmentGene expressionAutomated video analysisDrugSignal transductionDrug discoveryAgonistsDisordersDiscovery pipelineA molecular systems perspective on calcium oscillations beyond ion fluxes
Xiong D, Tong C, Wu M. A molecular systems perspective on calcium oscillations beyond ion fluxes. Current Opinion In Cell Biology 2025, 94: 102523. PMID: 40311263, PMCID: PMC12113571, DOI: 10.1016/j.ceb.2025.102523.Peer-Reviewed Original ResearchEmerging Concept of Receptor Endocytosis and Signaling
Kumar A, Panda A, Kumar S, Ranjan K. Emerging Concept of Receptor Endocytosis and Signaling. The Receptors 2025, 2: 61-84. DOI: 10.1007/978-3-031-81991-9_3.Peer-Reviewed Original ResearchReceptor endocytosisMaintenance of cell polarityRegulation of receptor internalizationRare human diseasesInternalization of ligand-receptor complexesMechanisms of endocytosisIntracellular signal transductionEndocytic adaptorsMembrane lipid compositionReceptor sortingEndocytic signalEndocytosis signalCell polarityCellular processesEndocytic mechanismsSignal transductionKinase proteinLigand-receptor complexesHuman diseasesEndocytosisEssential functionReceptor internalizationCellular environmentNutrient uptakeIntracellular mechanisms
2024
Spatiotemporal control of subcellular O-GlcNAc signaling using Opto-OGT
Ong Q, Lim L, Goh C, Liao Y, Chan S, Lim C, Kam V, Yap J, Tseng T, Desrouleaux R, Wang L, Ler S, Lim S, Kim S, Sobota R, Bennett A, Han W, Yang X. Spatiotemporal control of subcellular O-GlcNAc signaling using Opto-OGT. Nature Chemical Biology 2024, 21: 300-308. PMID: 39543398, PMCID: PMC12279475, DOI: 10.1038/s41589-024-01770-7.Peer-Reviewed Original ResearchO-GlcNAc transferaseO-GlcNAcLocalized to specific subcellular sitesResponse to insulin stimulationPost-translational modification of intracellular proteinsModification of intracellular proteinsO-GlcNAc signalingPost-translational modificationsTargeting O-GlcNAc transferaseSpatiotemporal controlMulticellular organismsOGT activityOrganelle functionO-GlcNAcylationSubcellular sitesMTORC activitySignal transductionIntracellular proteinsNutrient-sensing signalsCell signalingInsulin stimulationPlasma membraneGene expressionRegulatory mechanismsAkt phosphorylationA Molecular-Based Ecosystem to Improve Personalized Medicine in Patients with Chronic Myelomonocytic Leukemia (CMML)
Lanino L, Hunter A, Gagelmann N, Robin M, Sala C, Dall'Olio D, Gurnari C, Dall'Olio L, Wang Y, Pleyer L, Xicoy B, Montalban-Bravo G, Shih L, Haque T, Abdel-Wahab O, Geissler K, Bataller A, Bazinet A, Meggendorfer M, Casetti I, Sauta E, Travaglino E, Palomo L, Zamora L, Quintela D, Jerez A, Cornejo E, Garcia Martin P, Díaz-Beyá M, Avendaño Pita A, Roldan V, Fiallo Suarez D, Cerezo Velasco E, Calabuig M, Such E, Sanz G, Kubasch A, Castilla-Llorente C, Bulabois C, Souchet L, Awada H, Bernardi M, Chiusolo P, Curti A, Giaccone L, Onida F, Borin L, Passamonti F, Diral E, Vucinic V, Bergonzi G, Voso M, Hou H, Chou W, Yao C, Lin C, Tien H, Campagna A, Ubezio M, Russo A, Todisco G, Maggioni G, Tentori C, Buizza A, Asti G, Zampini M, Riva E, Delleani M, Consagra A, Ficara F, Santoro A, Carota L, Sanavia T, Rollo C, Kiwan A, VanOudenhove J, Fariselli P, Al Ali N, Sallman D, Kern W, Garcia-Manero G, Thota S, Griffiths E, Follo M, Finelli C, Platzbecker U, Sole F, Diez-Campelo M, Maciejewski J, Bejar R, Thol F, Kröger N, Fenaux P, Itzykson R, Graubert T, Fontenay M, Zeidan A, Komrokji R, Santini V, Haferlach T, Germing U, D'Amico S, Castellani G, Patnaik M, Solary E, Padron E, Della Porta M. A Molecular-Based Ecosystem to Improve Personalized Medicine in Patients with Chronic Myelomonocytic Leukemia (CMML). Blood 2024, 144: 1003-1003. DOI: 10.1182/blood-2024-200104.Peer-Reviewed Original ResearchChronic myelomonocytic leukemiaLeukemia-free survivalMyeloid neoplasmsProportion of patientsOverall survivalMolecular-based toolsMolecular informationEvaluation of mutation statusInfluence disease phenotypeGenomic overlapScoring systemGenomic associationsGenomic featuresSplicing machineryConcordance indexGenomic characterizationChronic myelomonocytic leukemia patientsMedian leukemia-free survivalProbability of disease relapseAllogeneic stem cell transplantationSignal transductionGenomic heterogeneityRisk of disease progressionMulti-color flow cytometryMutation screeningSomatic gene mutations involved in DNA damage response/Fanconi anemia signaling are tissue- and cell-type specific in human solid tumors
Kumar S, Du W, Zhang J, Yu H, Deng Y, Fei P. Somatic gene mutations involved in DNA damage response/Fanconi anemia signaling are tissue- and cell-type specific in human solid tumors. Frontiers In Medicine 2024, 11: 1462810. PMID: 39421870, PMCID: PMC11483370, DOI: 10.3389/fmed.2024.1462810.Peer-Reviewed Original ResearchDNA damage responsePotential driver mutationsFanconi anemiaCellular defense networkHuman cancersStudy of DNA damage responseAlteration frequencyDriver mutationsFA proteinsPan-cancer samplesSignal transductionSomatic gene mutationsDamage responseFA signalingUBE2TMutated genesCellular insultsDevelopment of effective therapeutic strategiesCell-typeMutational signaturesGene alteration patternsGenesMutationsDefense networkProstate cancerThe Caenorhabditis elegans protein SOC-3 permits an alternative mode of signal transduction by the EGL-15 FGF receptor
Rodriguez Torres C, Wicker N, Puccini de Castro V, Stefinko M, Bennett D, Bernhardt B, Garcia Montes de Oca M, Jallow S, Flitcroft K, Palalay J, Payán Parra O, Stern Y, Koelle M, Voisine C, Woods I, Lo T, Stern M, de la Cova C. The Caenorhabditis elegans protein SOC-3 permits an alternative mode of signal transduction by the EGL-15 FGF receptor. Developmental Biology 2024, 516: 183-195. PMID: 39173814, PMCID: PMC11488645, DOI: 10.1016/j.ydbio.2024.08.014.Peer-Reviewed Original ResearchC-terminal domainEGL-15MPK-1 activationSex myoblastsSem-5CLR-1SOC-1Regulating animal developmentMode of signal transductionPTP-2Cell signaling modulatorsCell-specific differencesRAS pathway activationTissue-specific mechanismsMPK-1IRS proteinsAnimal developmentSOC-3Homeostasis defectsCaenorhabditis elegansGenetic screeningHyp7Kinase RafSignal transductionFGF signalingInhibition of GSK3α,β rescues cognitive phenotypes in a preclinical mouse model of CTNNB1 syndrome
Alexander J, Vazquez-Ramirez L, Lin C, Antonoudiou P, Maguire J, Wagner F, Jacob M. Inhibition of GSK3α,β rescues cognitive phenotypes in a preclinical mouse model of CTNNB1 syndrome. EMBO Molecular Medicine 2024, 16: 2109-2131. PMID: 39103699, PMCID: PMC11393422, DOI: 10.1038/s44321-024-00110-5.Peer-Reviewed Original ResearchHeterozygous loss-of-function variantsLoss-of-function variantsWnt signal transductionWnt target gene expressionSynaptic adhesion complexesTarget gene expressionB-cateninCognitive phenotypesHeterozygous mouse linePreclinical mouse modelsWild-type littermatesBrain functionAdhesion complexesSignal transductionEfficacious treatmentNeuronal functional propertiesRegulation of changesGene expressionMotor deficitsHeterozygous miceN-cadherinNa/K-ATPaseBrainMotor disabilityMouse modelNonlinear dynamics in phosphoinositide metabolism
Fung S, Xǔ X, Wu M. Nonlinear dynamics in phosphoinositide metabolism. Current Opinion In Cell Biology 2024, 88: 102373. PMID: 38797149, PMCID: PMC11186694, DOI: 10.1016/j.ceb.2024.102373.Peer-Reviewed Original ResearchMetabolic networksPhosphoinositide metabolismNegative feedback loopCellular physiologyEnzymatic functionSignaling ComplexSignal transductionMembrane dynamicsNetwork motifsMetabolic pathwaysLipid fluxCellular behaviorMolecular circuitsPhosphoinositideFeedforward loopProducts of metabolismMetabolismFeedback loopExperimental challengeNonlinear dynamicsMotifFramework of nonlinear dynamicsTransductionExcited statesComprehensive understandingEGFR targeting PhosTACs as a dual inhibitory approach reveals differential downstream signaling
Hu Z, Chen P, Li W, Krone M, Zheng S, Saarbach J, Velasco I, Hines J, Liu Y, Crews C. EGFR targeting PhosTACs as a dual inhibitory approach reveals differential downstream signaling. Science Advances 2024, 10: eadj7251. PMID: 38536914, PMCID: PMC10971414, DOI: 10.1126/sciadv.adj7251.Peer-Reviewed Original ResearchConceptsInhibit cancer cell viabilityProteome-wide levelCancer cell viabilityDifferential signaling pathwaysPhosphoproteomic approachTyrosine dephosphorylationProtein dephosphorylationSignal transductionActivating dephosphorylationInduce apoptosisReceptor tyrosine kinase inhibitorsRTK activationSignaling pathwayInhibition of kinasesDephosphorylationEpidermal growth factor receptorGrowth factor receptorCell viabilityFactor receptorInhibitory approachesTyrosineTyrosine kinase inhibitorsInhibitory effectInhibitory potentialKinase inhibitorsMechanism of Insulin Action
White M. Mechanism of Insulin Action. 2024, 111-127. DOI: 10.1002/9781119697473.ch9.Peer-Reviewed Original ResearchReceptor tyrosine kinasesTyrosine kinaseGrowth factor signalingSecrete sufficient insulinDysregulated insulin signalingPancreatic beta cellsMuscle insulin resistanceEnvironmental signalsSignal transductionInsulin signalingMuscle-specific deletionSystemic insulin actionSystemic insulin resistanceAdequate insulin responseFactor signalingInsulin-like growth factor signalingPlasma membraneInsulin resistanceInsulin receptorLigand bindingBeta cellsMetabolic stressChronic insulin resistanceGlucose transportTransphosphorylation
2023
Separation of B- and T-Cell-Specific Signaling Molecules Prevents Oncogenic Transformation in Lymphoid Malignancies
Ketzer F, Klemm L, Robinson M, Loucks C, Arce D, Cosgun K, Kothari S, Müschen M. Separation of B- and T-Cell-Specific Signaling Molecules Prevents Oncogenic Transformation in Lymphoid Malignancies. Blood 2023, 142: 1396. DOI: 10.1182/blood-2023-189221.Peer-Reviewed Original ResearchKinase ZAP70Transcriptional regulationTranscription factorsKinase SykDownstream activationT-cell signaling proteinsCRISPR/Cas9-mediated knockoutComparative proteomic analysisNegative selectionFunction of proteinsWild-type cellsCas9-mediated knockoutCo-expressed proteinsPre-malignant cellsT cell linesCellular fitnessTranscription machinerySLP-76Signaling proteinsMalignant transformationSignal transductionAberrant transcriptionProteomic analysisChIP-qPCRNovel key mechanismStructure of the native chemotaxis core signaling unit from phage E-protein lysed E. coli cells
Cassidy C, Qin Z, Frosio T, Gosink K, Yang Z, Sansom M, Stansfeld P, Parkinson J, Zhang P. Structure of the native chemotaxis core signaling unit from phage E-protein lysed E. coli cells. MBio 2023, 14: e00793-23. PMID: 37772839, PMCID: PMC10653900, DOI: 10.1128/mbio.00793-23.Peer-Reviewed Original ResearchConceptsCore signalling unitChemosensory arraysLyse E. coli cellsCryo-electron tomographyBacterial chemotaxisSignal transductionCell movementEscherichia coli</i>.Sensing machinerySensory signal transductionSignaling unitStructural basisMolecular mechanismsMechanistic hypothesesDesign new experimentsChemotaxisCellsComplete structurePhageMotilityTransductionMachineryUbiquitous behaviorBiomolecular Condensation of SH2 Domain-Containing Proteins on Membranes
Zeng L, Su X. Biomolecular Condensation of SH2 Domain-Containing Proteins on Membranes. Methods In Molecular Biology 2023, 2705: 371-379. PMID: 37668985, DOI: 10.1007/978-1-0716-3393-9_20.Peer-Reviewed Original ResearchConceptsSH2 domainSH2 domain-containing proteinsDomain-containing proteinsT cell receptorReceptors/adaptorsReceptor pathwayContext of membraneEndomembrane systemMembrane receptor pathwaysSignal transductionBiomolecular condensationSpecific tyrosinePlasma membraneReconstitution systemGolgi apparatusEndoplasmic reticulumLiquid-liquid phase separationMultivalent interactionsCondensate formationProteinMembranePathwayPhosphotyrosineAssaysTransduction
2022
Rho family GTPase signaling through type II p21-activated kinases
Chetty A, Ha B, Boggon T. Rho family GTPase signaling through type II p21-activated kinases. Cellular And Molecular Life Sciences 2022, 79: 598. PMID: 36401658, PMCID: PMC10105373, DOI: 10.1007/s00018-022-04618-2.Peer-Reviewed Original ResearchConceptsRho family small GTPasesP21-activated kinaseRho GTPasesSmall GTPasesPAK family membersRho family GTPaseSignal transduction pathwaysMechanism of regulationPAK familySignal transductionTransduction pathwaysGTPasesMolecular basisDownstream effectorsDomain recognitionPAKsCross talkKinasePAK groupDistinct structuresRegulationPAKFamily membersGTPaseTransductionPRMT4-mediated arginine methylation promotes tyrosine phosphorylation of VEGFR-2 and regulates filopodia protrusions
Hartsough E, Shelke R, Amraei R, Aryan Z, Lotfollahzadeh S, Rahimi N. PRMT4-mediated arginine methylation promotes tyrosine phosphorylation of VEGFR-2 and regulates filopodia protrusions. IScience 2022, 25: 104736. PMID: 35942094, PMCID: PMC9356023, DOI: 10.1016/j.isci.2022.104736.Peer-Reviewed Original ResearchSrc homology domain 2Protein arginine methyltransferase 4N-terminal domain bindsFilopodia protrusionsVEGFR-2Arginine methylationDomain bindsVascular endothelial growth factor receptor 2 activationSignal transductionTyrosine phosphorylationC-SrcMolecular mechanismsDomain 2MethylationPhosphorylationAngiogenic signalingPathological angiogenesisReceptor 2 activationAngiogenic responseTumor angiogenesisVEGFR-2 inhibitorsEVH1AngiogenesisTransductionSignaling
2021
DnaJ and ClpX Are Required for HitRS and HssRS Two-Component System Signaling in Bacillus anthracis
Laut C, Leasure C, Pi H, Carlin S, Chu M, Hillebrand G, Lin H, Yi X, Stauff D, Skaar E. DnaJ and ClpX Are Required for HitRS and HssRS Two-Component System Signaling in Bacillus anthracis. Infection And Immunity 2021, 90: e00560-21. PMID: 34748369, PMCID: PMC8788696, DOI: 10.1128/iai.00560-21.Peer-Reviewed Original ResearchConceptsTwo-component systemGene expressionSubstrate-binding subunitSignal transduction activityTarget gene expressionB. anthracisBacillus anthracisGram-positive bacteriumHost-induced stressesClpXP proteaseProtein chaperonesSignal transductionClpXGene productsTransduction activityDnaJVertebrate hostsHeme levelsHomeostasis regulatorGenetic selectionHigh heme levelsCell envelope disruptionBioterror weaponHssRSAnthracisGenetic Landscape of Myeloproliferative Neoplasms with an Emphasis on Molecular Diagnostic Laboratory Testing
Easwar A, Siddon AJ. Genetic Landscape of Myeloproliferative Neoplasms with an Emphasis on Molecular Diagnostic Laboratory Testing. Life 2021, 11: 1158. PMID: 34833034, PMCID: PMC8625510, DOI: 10.3390/life11111158.Peer-Reviewed Original ResearchAdditional mutationsChromatin modificationsSignal transductionDNA methylationPhiladelphia chromosome-negative myeloproliferative neoplasmsJAK-STATConstitutive activationGenetic landscapeDriver eventsMyeloproliferative neoplasmsSomatic mutationsMolecular landscapeMutationsMolecular alterationsHematopoietic stem cell neoplasmsSplicingTransductionGenesMethylationLandscapeSequencing panelTranslocationStem cell neoplasmChronic myeloid leukemiaPathwayPhase separation in immune signalling
Xiao Q, McAtee CK, Su X. Phase separation in immune signalling. Nature Reviews Immunology 2021, 22: 188-199. PMID: 34230650, PMCID: PMC9674404, DOI: 10.1038/s41577-021-00572-5.Peer-Reviewed Original ResearchConceptsGene I proteinImmune signaling pathwaysCyclic GMP-AMP synthaseSubstantial conformational changesNew biophysical principleGMP-AMP synthaseCell receptorB cell receptorCytosolic eventsSignal transductionImmune signalingSignaling pathwaysI proteinConformational changesLigand engagementDownstream adaptorsInterferon genesImmune receptorsBiophysical principlesLiquid-liquid phase separationFunctional consequencesT cell receptorPathogenic stimuliSpatial reorganizationOutstanding questionsHow the PhoP/PhoQ System Controls Virulence and Mg2+ Homeostasis: Lessons in Signal Transduction, Pathogenesis, Physiology, and Evolution
Groisman EA, Duprey A, Choi J. How the PhoP/PhoQ System Controls Virulence and Mg2+ Homeostasis: Lessons in Signal Transduction, Pathogenesis, Physiology, and Evolution. Microbiology And Molecular Biology Reviews 2021, 85: 10.1128/mmbr.00176-20. PMID: 34191587, PMCID: PMC8483708, DOI: 10.1128/mmbr.00176-20.Peer-Reviewed Original ResearchConceptsPhoP/PhoQ systemPhoP/PhoQSignal transductionAbundance of hundredsGram-negative bacterial speciesTwo-component systemSalmonella enterica serovar TyphimuriumRegulatory RNAsEnterica serovar TyphimuriumTranscription factorsProtease regulatorsTranscriptional effectsCationic antimicrobial peptidesInducing conditionsBacterial speciesSerovar TyphimuriumPhysiological consequencesAntimicrobial peptidesPhoQTransductionVirulenceHomeostasisAbundanceNovel formPhoP
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