2021
Wet-dry-wet drug screen leads to the synthesis of TS1, a novel compound reversing lung fibrosis through inhibition of myofibroblast differentiation
Ring NAR, Volpe MC, Stepišnik T, Mamolo MG, Panov P, Kocev D, Vodret S, Fortuna S, Calabretti A, Rehman M, Colliva A, Marchesan P, Camparini L, Marcuzzo T, Bussani R, Scarabellotto S, Confalonieri M, Pham TX, Ligresti G, Caporarello N, Loffredo FS, Zampieri D, Džeroski S, Zacchigna S. Wet-dry-wet drug screen leads to the synthesis of TS1, a novel compound reversing lung fibrosis through inhibition of myofibroblast differentiation. Cell Death & Disease 2021, 13: 2. PMID: 34916483, PMCID: PMC8677786, DOI: 10.1038/s41419-021-04439-4.Peer-Reviewed Original ResearchConceptsAnti-fibrotic effectsDopamine receptor 3Lung fibrosisMyofibroblast activationReceptor 3Idiopathic pulmonary fibrosis patientsMyofibroblast differentiationPulmonary fibrosis patientsProgression of fibrosisTransforming Growth Factor-β PathwayGrowth factor β pathwayHigh-throughput screenDisease progressionMurine modelFibrosisFibrosis patientsFibrotic diseasesDrug screensLung fibroblastsNovel compoundsProgressionΒ pathwayImportant targetDopaminePrimary fibroblastsA ligand-insensitive UNC5B splicing isoform regulates angiogenesis by promoting apoptosis
Pradella D, Deflorian G, Pezzotta A, Di Matteo A, Belloni E, Campolungo D, Paradisi A, Bugatti M, Vermi W, Campioni M, Chiapparino A, Scietti L, Forneris F, Giampietro C, Volf N, Rehman M, Zacchigna S, Paronetto MP, Pistocchi A, Eichmann A, Mehlen P, Ghigna C. A ligand-insensitive UNC5B splicing isoform regulates angiogenesis by promoting apoptosis. Nature Communications 2021, 12: 4872. PMID: 34381052, PMCID: PMC8358048, DOI: 10.1038/s41467-021-24998-6.Peer-Reviewed Original ResearchConceptsSplicing isoformsNetrin-1 bindingAlternative splicing factorPost-transcriptional pathwayNetrin-1 receptor UNC5BBlood vessel developmentEndothelial cellsApoptosis-dependent mannerSplicing factorsApoptotic functionTumor angiogenesisNetrin-1Vascular developmentVessel developmentInduces ApoptosisReceptor UNC5BIsoformsApoptosisUNC5BAngiogenesisExonsRegulatorPoor patient outcomesCancer vasculaturePathwayA Polyphenol-Rich Extract of Olive Mill Wastewater Enhances Cancer Chemotherapy Effects, While Mitigating Cardiac Toxicity
Albini A, Festa M, Ring N, Baci D, Rehman M, Finzi G, Sessa F, Zacchigna S, Bruno A, Noonan D. A Polyphenol-Rich Extract of Olive Mill Wastewater Enhances Cancer Chemotherapy Effects, While Mitigating Cardiac Toxicity. Frontiers In Pharmacology 2021, 12: 694762. PMID: 34434106, PMCID: PMC8381749, DOI: 10.3389/fphar.2021.694762.Peer-Reviewed Original ResearchHearts of miceSide effectsRat cardiomyocytesPotential cardioprotective activityEffect of chemotherapyProstate cancer xenograftsAdverse side effectsColon cancer cell growthCancer cell growthPolyphenol-rich extractAnti-oxidant activityAnti-cancer activityCardiovascular preventionCardioprotective effectsTumor weightCardiac toxicityCancer patientsCardiovascular toxicityCancer xenograftsCardioprotective roleProtective effectCancer chemotherapy effectsMouse pupsCardioprotective activityChemotherapy effectA Polyphenol-Rich Extract of Olive Mill Wastewater Enhances Cancer Chemotherapy Effects, While Mitigating Cardiac Toxicity
Albini Adriana, Festa Marco M. G., Ring Nadja, Baci Denisa, Rehman Michael, Finzi Giovanna, Sessa Fausto, Zacchigna Serena, Bruno Antonino, Noonan Douglas M.Peer-Reviewed Original Research
2020
Genetic lineage tracing reveals poor angiogenic potential of cardiac endothelial cells
Kocijan T, Rehman M, Colliva A, Groppa E, Leban M, Vodret S, Volf N, Zucca G, Cappelletto A, Piperno GM, Zentilin L, Giacca M, Benvenuti F, Zhou B, Adams R, Zacchigna S. Genetic lineage tracing reveals poor angiogenic potential of cardiac endothelial cells. Cardiovascular Research 2020, 117: 256-270. PMID: 31999325, PMCID: PMC7797216, DOI: 10.1093/cvr/cvaa012.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsApelinCalcium-Binding ProteinsCell Line, TumorCell LineageCell ProliferationCellular MicroenvironmentCoronary VesselsEndothelial CellsMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicMuscle, SkeletalNeoplasmsNeovascularization, PathologicNeovascularization, PhysiologicPhenotypeReceptor, Notch1Tumor BurdenTumor MicroenvironmentVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1ConceptsGenetic lineage tracingCardiac endothelial cellsPro-angiogenic stimuliEndothelial cellsAngiogenic responseSkeletal muscleCardiac ischaemiaApelin expressionLineage tracingAngiogenic potentialCancer cellsVascular endothelial growth factorMyocardial infarction resultsReduced tumor angiogenesisEndothelial growth factorPro-angiogenic moleculesSurgical revascularizationInfarction resultsClinical trialsContractile functionNew arteriolesSame doseTumor massTherapeutic revascularizationCardiomyocyte death
2019
Rhomboid-Like-2 Intramembrane Protease Mediates Metalloprotease-Independent Regulation of Cadherins
Battistini C, Rehman M, Avolio M, Arduin A, Valdembri D, Serini G, Tamagnone L. Rhomboid-Like-2 Intramembrane Protease Mediates Metalloprotease-Independent Regulation of Cadherins. International Journal Of Molecular Sciences 2019, 20: 5958. PMID: 31783481, PMCID: PMC6928865, DOI: 10.3390/ijms20235958.Peer-Reviewed Original ResearchConceptsE-cadherin extracellular domainIntramembrane proteasesExtracellular domainPost-translational regulationSame functional pathwayRhomboid familyRHBDL2Tissue homeostasisNovel regulatorCell motilityNegative regulatorFunctional pathwaysCadherinMajor familiesCell migrationAdhesive receptorsFunctional roleNovel mechanismVE-cadherinNovel MMPsE-cadherinCancer cellsRegulatorProteaseEndothelial cellsmiR-200 family members reduce senescence and restore idiopathic pulmonary fibrosis type II alveolar epithelial cell transdifferentiation
Moimas S, Salton F, Kosmider B, Ring N, Volpe MC, Bahmed K, Braga L, Rehman M, Vodret S, Graziani ML, Wolfson MR, Marchetti N, Rogers TJ, Giacca M, Criner GJ, Zacchigna S, Confalonieri M. miR-200 family members reduce senescence and restore idiopathic pulmonary fibrosis type II alveolar epithelial cell transdifferentiation. ERJ Open Research 2019, 5: 00138-2019. PMID: 31857992, PMCID: PMC6911923, DOI: 10.1183/23120541.00138-2019.Peer-Reviewed Original ResearchIdiopathic pulmonary fibrosisMiR-200 family membersEpithelial-mesenchymal transitionATII cellsEMT markersATI cellsMarker expressionFamily membersRegenerative potentialAlveolar type II cellsType II cellsIPF patientsSenescence marker expressionIPF lungsMiR-200 familyPulmonary fibrosisEpithelial cell transdifferentiationCell markersImpaired expressionFamilial casesCell transdifferentiationII cellsSenescent phenotypeMicroRNA effectsTransdifferentiationLoss of Protein Kinase Csnk2b/CK2β at Neuromuscular Junctions Affects Morphology and Dynamics of Aggregated Nicotinic Acetylcholine Receptors, Neuromuscular Transmission, and Synaptic Gene Expression
Eiber N, Rehman M, Kravic B, Rudolf R, Sandri M, Hashemolhosseini S. Loss of Protein Kinase Csnk2b/CK2β at Neuromuscular Junctions Affects Morphology and Dynamics of Aggregated Nicotinic Acetylcholine Receptors, Neuromuscular Transmission, and Synaptic Gene Expression. Cells 2019, 8: 940. PMID: 31434353, PMCID: PMC6721821, DOI: 10.3390/cells8080940.Peer-Reviewed Original ResearchConceptsSynaptic gene expressionGene expressionNicotinic acetylcholine receptorsClustering of AChRsNeuromuscular junctionCultured muscle cellsAcetylcholine receptorsDistinctive proteinsCK2Neuromuscular transmissionAChR clustersΒ-subunitCompound muscle action potentialHigh turnover rateCK2βCell proliferationMuscle action potentialsNMJ fragmentationSkeletal muscle fibersPrecise roleAge-dependent decreaseMuscle cellsAcetylcholine esterase inhibitorsAChRExpressionHigh-throughput screening discovers antifibrotic properties of haloperidol by hindering myofibroblast activation
Rehman M, Vodret S, Braga L, Guarnaccia C, Celsi F, Rossetti G, Martinelli V, Battini T, Long C, Vukusic K, Kocijan T, Collesi C, Ring N, Skoko N, Giacca M, Del Sal G, Confalonieri M, Raspa M, Marcello A, Myers MP, Crovella S, Carloni P, Zacchigna S. High-throughput screening discovers antifibrotic properties of haloperidol by hindering myofibroblast activation. JCI Insight 2019, 4: e123987. PMID: 30996132, PMCID: PMC6538355, DOI: 10.1172/jci.insight.123987.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCalciumCell DifferentiationCells, CulturedDisease Models, AnimalDrug RepositioningEndoplasmic Reticulum StressFibrosisHaloperidolHumansIntravital MicroscopyLungMiceMyocardiumMyofibroblastsOptical ImagingPrimary Cell CultureReceptor, Notch1Receptors, sigmaRNA InterferenceRNA, Small InterferingSignal TransductionConceptsMyofibroblast activationSigma receptor 1Smooth muscle actinDifferent animal modelsTransforming Growth FactorDiscovery of haloperidolTumor-associated fibrosisMechanism of actionEndoplasmic reticulum stress responseFibrotic burdenAntifibrotic effectsAntifibrotic propertiesCommon antipsychotic drugsAntipsychotic drugsFibrotic processIntracellular calciumReticulum stress responseAnimal modelsMuscle actinFibrotic conditionsHaloperidolReceptor 1Growth factorContractile proteinsTherapeutic solutions
2018
Paracrine effect of regulatory T cells promotes cardiomyocyte proliferation during pregnancy and after myocardial infarction
Zacchigna S, Martinelli V, Moimas S, Colliva A, Anzini M, Nordio A, Costa A, Rehman M, Vodret S, Pierro C, Colussi G, Zentilin L, Gutierrez MI, Dirkx E, Long C, Sinagra G, Klatzmann D, Giacca M. Paracrine effect of regulatory T cells promotes cardiomyocyte proliferation during pregnancy and after myocardial infarction. Nature Communications 2018, 9: 2432. PMID: 29946151, PMCID: PMC6018668, DOI: 10.1038/s41467-018-04908-z.Peer-Reviewed Original ResearchConceptsRegulatory T cellsMyocardial infarctionTreg depletionCardiomyocyte proliferationT cellsRole of TregsDepressed cardiac functionFetal cardiomyocyte proliferationPregnancy decreasesInfarct sizeMaternal toleranceMassive inflammationPregnant mothersCardiac functionMaternal bloodTherapeutic effectParacrine mannerTregsCollagen depositionParacrine effectsPregnant animalsInfarctionProliferationCardiomyocytesProliferative cardiomyocytesUnderstanding the poor angiogenic capacity of the mammalian heart
Kocijan T, Cappelletto A, Rehman M, Tang Y, Vodret S, Zentilin L, Giacca M, Zacchigna S. Understanding the poor angiogenic capacity of the mammalian heart. Vascular Pharmacology 2018, 103: 58-59. DOI: 10.1016/j.vph.2017.12.032.Peer-Reviewed Original ResearchTaming the Notch Transcriptional Regulator for Cancer Therapy
Tamagnone L, Zacchigna S, Rehman M. Taming the Notch Transcriptional Regulator for Cancer Therapy. Molecules 2018, 23: 431. PMID: 29462871, PMCID: PMC6017063, DOI: 10.3390/molecules23020431.Peer-Reviewed Original Research
2016
PlexinD1 Is a Novel Transcriptional Target and Effector of Notch Signaling in Cancer Cells
Rehman M, Gurrapu S, Cagnoni G, Capparuccia L, Tamagnone L. PlexinD1 Is a Novel Transcriptional Target and Effector of Notch Signaling in Cancer Cells. PLOS ONE 2016, 11: e0164660. PMID: 27749937, PMCID: PMC5066946, DOI: 10.1371/journal.pone.0164660.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzazepinesCadherinsCell Adhesion Molecules, NeuronalCell Line, TumorCell MovementDiaminesDown-RegulationEnzyme InhibitorsHEK293 CellsHuman Umbilical Vein Endothelial CellsHumansIntracellular Signaling Peptides and ProteinsJagged-1 ProteinLung NeoplasmsMembrane GlycoproteinsMiceMice, Inbred NODMice, SCIDMicroscopy, FluorescencePromoter Regions, GeneticReceptors, NotchRNA InterferenceRNA, MessengerRNA, Small InterferingSignal TransductionSnail Family Transcription FactorsThiazolesTransplantation, HeterologousUp-RegulationConceptsNovel transcriptional targetProstate cancer cell migrationCell migrationCancer cell migrationTranscriptional targetsNotch signalingPlexinD1 expressionE-cadherin levelsCancer cellsProstate cancer cellsE-cadherin regulationAbsence of NotchPromoter activity reporterCancer cell invasivenessTranscription factor SlugProstate cancerProstate cancer cell invasivenessTranscriptional activationNotch receptorsActivity reporterDownstream eventsAxis downstreamNotch ligandsFunctional rescuePlexinD1
2013
To Die or Not to Die: Sema3E Rules the Game
Tamagnone L, Rehman M. To Die or Not to Die: Sema3E Rules the Game. Cancer Cell 2013, 24: 564-566. PMID: 24229706, DOI: 10.1016/j.ccr.2013.10.010.Peer-Reviewed Original Research
2012
Semaphorins in cancer: Biological mechanisms and therapeutic approaches
Rehman M, Tamagnone L. Semaphorins in cancer: Biological mechanisms and therapeutic approaches. Seminars In Cell And Developmental Biology 2012, 24: 179-189. PMID: 23099250, DOI: 10.1016/j.semcdb.2012.10.005.Peer-Reviewed Original ResearchConceptsResponsive cell typesHallmarks of cancerMultiple experimental approachesEpigenetic changesSemaphorin signalsPhysiological processesCell migrationPivotal signalsCell typesReceptor complexCell proliferationSemaphorinsCancer cellsDifferent semaphorinsBiological mechanismsHuman tumorsTumor progressionMultiple alterationsTumor angiogenesisPathwayExperimental approachFamily membersTumor microenvironmentImportant roleCellsProteome-wide Analysis of Lysine Acetylation Suggests its Broad Regulatory Scope in Saccharomyces cerevisiae *
Henriksen P, Wagner SA, Weinert BT, Sharma S, Bačinskaja G, Rehman M, Juffer AH, Walther TC, Lisby M, Choudhary C. Proteome-wide Analysis of Lysine Acetylation Suggests its Broad Regulatory Scope in Saccharomyces cerevisiae *. Molecular & Cellular Proteomics 2012, 11: 1510-1522. PMID: 22865919, PMCID: PMC3494197, DOI: 10.1074/mcp.m112.017251.Peer-Reviewed Original ResearchConceptsAcetylation sitesLysine acetylationS. cerevisiaeUnicellular eukaryotic model organismBudding yeast Saccharomyces cerevisiaeRegulatory roleBroader regulatory scopeProtein synthesisEukaryotic model organismYeast Saccharomyces cerevisiaePost-translational modificationsLysine acetylation sitesImportant regulatory roleChromatin organizationLysine acetyltransferasesModel organismsWide analysisPutative substratesRegulatory domainCritical regulatory domainsHistone H2BAcetylated proteinsProtein foldingSaccharomyces cerevisiaeBioinformatics analysis
2011
Eisosome-driven plasma membrane organization is mediated by BAR domains
Ziółkowska NE, Karotki L, Rehman M, Huiskonen JT, Walther TC. Eisosome-driven plasma membrane organization is mediated by BAR domains. Nature Structural & Molecular Biology 2011, 18: 854-856. PMID: 21685922, DOI: 10.1038/nsmb.2080.Peer-Reviewed Original Research
2010
A plasma-membrane E-MAP reveals links of the eisosome with sphingolipid metabolism and endosomal trafficking
Aguilar PS, Fröhlich F, Rehman M, Shales M, Ulitsky I, Olivera-Couto A, Braberg H, Shamir R, Walter P, Mann M, Ejsing CS, Krogan NJ, Walther TC. A plasma-membrane E-MAP reveals links of the eisosome with sphingolipid metabolism and endosomal trafficking. Nature Structural & Molecular Biology 2010, 17: 901-908. PMID: 20526336, PMCID: PMC3073498, DOI: 10.1038/nsmb.1829.Peer-Reviewed Original ResearchConceptsGDP/GTP exchange factorQuantitative genetic interaction mapGenetic interaction mapSphingolipid metabolismGTP exchange factorExchange factorMotif analysisEndosomal traffickingMembrane biologyInteraction mapEisosomesE-MAPGenesRom2MetabolismRho1New componentsTraffickingBiologyRegulationRhO2UncoversIdentification
2009
Notch1 regulates the functional contribution of RhoC to cervical carcinoma progression
Srivastava S, Ramdass B, Nagarajan S, Rehman M, Mukherjee G, Krishna S. Notch1 regulates the functional contribution of RhoC to cervical carcinoma progression. British Journal Of Cancer 2009, 102: 196-205. PMID: 19953094, PMCID: PMC2813755, DOI: 10.1038/sj.bjc.6605451.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnoikisCarcinoma, Squamous CellCell DivisionCell Line, TumorCell MovementCell TransdifferentiationDisease ProgressionFemaleGene Knockdown TechniquesHumansMiceMice, NudeNeoplasm InvasivenessNeoplasm ProteinsNeovascularization, PathologicReceptor, Notch1Rho GTP-Binding ProteinsRhoC GTP-Binding ProteinRNA, Small InterferingSignal TransductionTumor Stem Cell AssayUterine Cervical NeoplasmsConceptsCervical carcinoma progressionRhoC protein expressionHuman cervical cancerCervical carcinoma cell linesPro-oncogenic roleHuman epithelial cancersNotch1 inactivationCervical cancerCarcinoma cell linesCervical carcinomaImmunohistochemical studyRole of NotchActive RhoCEpithelial cancersCarcinoma progressionSiHa cellsMesenchymal transitionNotch1 inhibitionWestern blottingProtein expressionClinical sectionTumor formationRhoC expressionColony formationTube formationLysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions
Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M. Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions. Science 2009, 325: 834-840. PMID: 19608861, DOI: 10.1126/science.1175371.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAmino Acid MotifsBenzamidesCell Line, TumorCell NucleusCell Physiological PhenomenaCytoplasmEnzyme InhibitorsHistone Deacetylase InhibitorsHistone DeacetylasesHumansHydroxamic AcidsLysineMass SpectrometryMetabolic Networks and PathwaysMitochondriaMultiprotein ComplexesProtein Processing, Post-TranslationalProtein Structure, TertiaryProteinsProteomeProteomicsPyridinesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsVorinostatConceptsLysine acetylationCellular rolesPosttranslational modificationsCyclin-dependent kinase Cdc28Phosphorylation-dependent interactionReversible posttranslational modificationDiverse cellular processesMajor cellular functionsTarget protein complexesMajor posttranslational modificationLarge macromolecular complexesLysine acetylation sitesChromatin remodelingActin nucleationNuclear transportProtein complexesCellular functionsCellular processesAcetylation sitesMacromolecular complexesAcetylation changesGene expressionCell cycleDeacetylase inhibitorsAcetylation