Centre for Biomedical Research (CBMR)

Research Groups

STEMCELLANDDEVELOPMENTRESEARCHGROUPRG-4773-2803A-StructureoftheresearchgroupTheStemCellandDevelopment(SCD)groupresultsfromthefusionoftheSTEMCELLBIOLOGYand the DEVELOPMENT AND CELL BIOLOGY Groups as proposed by the evaluators of theoriginal CBMR project proposal in 2013. The SCD group coordinated by Dr José Bragança isorganizedaround7laboratoriesthatarepartofCBMR:1-STEMCELLBIOLOGYLAB–ProfDrJoséBragança.Currentresearch interests:mechanismsofpluripotency,earlyspecification intomesodermandcardiaccelllineagesofembryonicstemcells.2-NEUROGENESISLAB–ProfDrInêsAraújo.Current research interests: injury-induced neurogenesis and promotion of survival bymodificationofthebiologicalsystemsbynitricoxideandcalpains.3-CHRONOBIOLOGYLAB–ProfDrIsabelPalmeirim.Current research interests: Interrelations between embryonic, circadian and cell-cycle clocksusing human umbilical cord mesenchymal stem cells as a novel model; evolution of vertebraformationandsomitogenesis.4-DROSOPHILADEVELOPMENTLAB–ProfDrRuiMartinho.Current research interests: understanding female germ line development and embryonicmid-blastula transition.Morespecifically, theregulationofgeneexpressionduringmeiosisand fastcellproliferation.5-MICROBIOLOGYRESEARCHLAB–ProfDrLeonorFaleiro.Current research interests: Link betweenmicrobiota and the development of type 1 diabetes.Impactofantibioticresistanceonfoodbornepathogens.6-TEMPORALCONTROLOFCELLDIFFERENTIATIONLAB–ProfDrRaquelP.Andrade.Currentresearch interests:understandinghowtherhythm/tempoofcelldifferentiationoccursbymappingclockgeneinteractionsandregulatorynetworksduringgastrulationusingthechickembryo.7-MOLECULARANDREGENERATIVEMEDICINELAB-ProfDrGustavoTiscornia.Currentresearchinterests:mechanismsofregenerationusingAcomysspinymouse.GaucherandParkinson diseases modelling using induced pluripotent stem cells (iPSC) and iPSC-derivedneurons.Screenforchaperonemolecules.B-ResearchoverviewThe SCD group has a strong expertise in the fields of: i) embryonic development through theinvestigationofavarietyofanimalmodels;ii)biologyofstemcells;iii)anddiseasesmodelling.The research interests of all labs composing the SCD group converge on understandingcardiovascular,neural,skeletalandmetabolicdisorders.AmajoraimoftheSCDgroupistodevelopnovelandcomplementaryanimalandcell-based systems to understand the molecular mechanisms underlying these biologicalevents/disorders. Inparticular, theSCDgroupwillwork towards theestablishmentof in vitroorganoidtissuesfrompluripotentstemcells.In particular, intestinal crypt organoids would be a powerful model to study the molecular,physicalandphysiological interactionsexistingbetweenthegutmicrobiotaofdiabeticpatientsor unaffected individuals and intestinal epithelia. Three-dimensional organoid models ofcardiovascular tissue would be useful to understand the contribution of genetic alterations(identifiedinanimalmodelsorindividualswithcardiomyopathies)inthecorrectdevelopment,as well as the temporal and structural maintenance of the organization and function of thecardiac tissue. Cerebral organoids would be useful to model human neural organization and(excessive)activityandstudytheeffectofcerebrallesions.Moreover,theabilitytoderivesuchorganoidtissueswillbenefitotherCBMRresearchgroups,suchastheoncologyandbiomedicine

researchgroupsprovidingmodelsoftumorigenictissuesandtissuestoassessfortoxicityeffectsforexample.Another ambitious goal of theCBMR is to intensify and expand the collaborationsbetween itsresearchersandpartnercliniciansattheregionalHospitalsinordertodevelopprojectsaimingatansweringclinicalissuesandtopromotetranslationalresearch.AlthoughproperflagshiptopicsofinterestforboththeSCDgroupandcliniciansremaintobeidentifiedandimplemented,littlecollaboration between researchers of the SCD group and clinicians are already ongoing,particularlyindiabetesandcardiovasculardomains.Therefore, thesetwodomainsmaybeconsideredaseasiertoexpandandprivilegedchoicestoreinforcetheinvolvementofmorelabsoftheSCDgroup.C-Productivity2014-presentThe members of the SCD group have published a total of 46 articles and 3 book chapters.Amongstthesepublications,4involvedcollaborationsbetweenlabsoftheSCDgroup.Duringthisperiod,thearticlespublishedbySCDgroupmembershavebeencited∼1600times(∼3600timessince2011;WebofScience).Sixarticlesarecurrentlysubmitted,and4areacceptedwithmajorrevisions.

• Projects funded by FCT and Maratona da Saúde to a total of 610 k€ for 4 projectscoordinated by 4 SCD groupmembers, and 2 othermemberswere co-applicants in 2grantsfundedbyFCT(totalof389k€).

• Supervised9Post-Docs,17PhDstudents(3completed),7MScstudents.• Organized5conferences(1internationalmeeting)andparticipatedatleastin9events

forScienceawarenesstothegeneralpublic.D-CollaborationsThe evaluation committee of the CBMR, pointed out that therewere few examples of positiveoutcomesregardingcollaborationsbetweentheCBMRandothergroupsinAlgarve,Portugalandabroad.However,themembersoftheSCDgrouphaveongoingcollaborations:-withintheUniversityofAlgarveandHospitalofFaro:3

• 4 collaborations are established with CBMR group members, 3 with members of theCCMAR(UAlg),3withtheFacultyofSciences(UAlg),1HealthSchool(UAlg)and2withcliniciansoftheHospitalofFaro.

• Thesecollaborationshaveresultedin7commonpublications,2papersunderrevision,2paperssubmitted,2grants,4grantproposals,aswellasfundingfor2Post-Docfellows,2PhDstudentswhichareco-supervisedand3MScprojectco-supervision.2proposalsforPhDfellowship.

-withnationalinstitutions:• 1collaborationhasbeenestablishedwiththeCEDOC(Lisbon),2withtheUniversityof

Coimbra,1withtheUniversityofMinho,1withtheUniversityofLisbon,1withtheIMM(Lisbon),1withtheIGC(Lisbon),1withtheINSA-Porto.

• Thesecollaborationshaveresultedin4publications,2publicationssubmitted,3grantsandfundingfor4co-supervisedPhDstudents,and1post-doctoralfellowship

-withinternationalinstitutions:

• 1 with the CABIMER (Spain), 1 with the Hospital de La Princesa (Spain), 2 with theUniversityofEdinburgh(UK),1withUCL(UK),1withtheUniversityofCambridge(UK),1 with John Innes Centre (UK), 1 with the University of Leicester (UK), 1 with KingsCollege (UK), 1 with the IMB gGmbH (Germany), 1 with the University of Bergen(Norway),1withtheUniversityofGhent(Belgium),1withUniversityofAlbany(USA),1withHarvardUniversity(USA),1withtheRikenBrainInstitute(Japan)

• Thesecollaborationshaveresultedin7publications,1articlesubmittedunderrevision,7 articles inpreparation, 3 grantproject funded, and funding for3 co-supervisedPhDstudents.

E–Pubications2014–present

Magno R, Andrade RP, Palmeirim I (2016). RDML Importer: Real-Time qPCR Data MarkupLanguageimporter.TheMathematicaJournal(acceptedforpublication).

PintoF,Pértega-GomesN,VizcaínoJR,AndradeRP,CárcanoFM,ReisRM.(2016).Brachyuryasapotential modulator of androgen receptor activity and a key player in therapy resistance inprostatecancer.OncotargetDOI:10.18632/oncotarget.8499.

MachadoNJ, SimõesAP, SilvaHB,ArdaisAP,KAsterMP,GarçãoP,RodriguesDI,PochmannD,SantosAI,AraújoIM,PorciúnculaOL,ToméAR,KofalviA,VaugeoisJ-M,AgostinhoP,ElYacoubiM, Cunha RA, Gomes CA (2016) Caffeine reverts memory but not mood impairment in bred-based depressed mice with up-regulated adenosine A2A receptor in hippocampal glutamatesynapses.MolecularNeurobiology(epubFebruary9,2016).

Paulo Navarro-Costa, Alicia McCarthy, Pedro Prudêncio, Gastón Guilgur, Jörg D. Becker,Prashanth Rangan and Rui G. Martinho (2016). Early programming of the oocyte epigenometemporally controls late prophase I transcription and chromatin architecture. NatureCommunications.

OmSinghRathore,AlexandraFaustino,PedroPrudêncio,PetraVanDamme,Cymon J. Cox,RuiGonçaloMartinho.SciRep.2016Feb10;6:21304.doi:10.1038/srep21304.

Caroline J. Sheeba, Raquel P. Andrade and Isabel Palmeirim. 2016. Mechanisms of vertebrateembryo segmentation: Common themes in trunk and limb development. Semin Cell Dev Biol.49:125–134.

Caroline J. Sheeba,RaquelP.Andradeand IsabelPalmeirim.2016.Gettingahandleonembryolimbdevelopment:Molecularinteractionsdrivinglimboutgrowthandpatterning.SeminCellDevBiol.49:92-101.

MatiasDS,MartinsAR,Csanellas I,OvaAB,AraújoIM,PowerD,TiscorniaG(2016)EarwoundregenerationintheAfricanSpinyMouseAcomyscahirinus.Regeneration3(1):52-61.

AdrianaGuerreiro,CustódiaGago,MariaG.C.Miguel,M.LeonorFaleiroandMariaD.C.Antunes.Theinfluenceofediblecoatingsenrichedwithcitralandeugenolontheraspberrystorageability,nutritionalandsensoryquality.FoodPackagingandShelfLife(2016)9:20-28.

SoukainaEl-Guendouz,AazzaSmail,BadiaâLyoussi,MariaDCAntunes,M.LeonorFaleiroandMaria Miguel (2016). Anti-acetylcholinesterase, antidiabetic, anti-inflammatory, antityrosinaseandantixanthineoxidaseactivitiesofMoroccanpropolis.InternationalJournalofFoodScience&Technology·June2016.

MarcosdeSouzaGomes,MariadasGraçasCardoso,AnaClaraG.Guimarães,AdrianaGuerreiro,EduardoV.B.V.Boas,CristinaMariaBarrocasDias,AnaManhita,M.LeonorFaleiro,MariaGraçaC.Miguel,MariaD.C.Antunes(2016).Ediblecoatingswithessentialoilseffectonthequalityofredraspberriesovershelf-life.JournaloftheScienceofFoodandAgriculture·May2016.

Nada Bahloul, Sana Bellili, Aazza Smail, Ameur Cherif, M. Leonor Faleiro, Maria D C Antunes,MariaMiguel,WissemMnif(2016).AqueousExtractsfromTunisianDiplotaxis:PhenolContent,Antioxidant and AntiAcetylcholinesterase Activities, and Impact of Exposure to SimulatedGastrointestinalFluids.Antioxidants2016,5(2),12;doi:10.3390/antiox5020012.

AdrianaC.Guerreiro,CustódiaM.L.Gago,M.LeonorFaleiro,MariaG.C.MiguelandMariaD.C.Antunes(2016)..Ediblecoatingsenrichedwithessentialoilsforextendingtheshelf-lifeof‘BravodeEsmolfe’fresh-cutapples.InternationalJournalofFoodScience&Technology(2016)51,87–95.

MariaGraçaMiguel , SmailAazza,MariaDulceAntunes,MariaLeonorFaleiro, JoséG.Barroso,LuisG.Pedro,A.CristinaFigueiredo(2016).Mineralandvolatilecompositionofágua-mel fromPortugal.European67FoodResearchandTechnology(2016)242,pp171-178.

Carreira BP, Santos DF, Santos AI, Carvalho CM, Araújo IM (2015) Nitric oxide regulatesneurogenesisinthehippocampusfollowingseizures.OxidativeMedicineandCellularLongevity2015:451512.

Machado-OliveiraG,GuerreiraE,MatiasAC,Facucho-OliveiraJ,Pacheco-LeyvaIandBragançaJ-“FBXL5 modulates HIF-1 transcriptional activity by degradation of CITED2” – Arch. Biochem.Biophys.,(2015)576,61-72.

BragançaJandSantosJMA–“IsCITED2ageneralregulatorofstemcellfunctions?”–StemCellTransl.Invest.,2015;2:e755.

Simões B, Conceição N, Matias AC, Bragança J, Kelsh RN and Cancela ML – “Molecularcharacterization of Cbf gene and identification of new transcription variants: Implications forfunction”–Arch.Biochem.Biophys.,567,1-12(2015).

KrancKR, OliveiraDV, Armesilla-DiazA, Pacheco-Leyva I,Matias AC, EscapaAL, Subramani C,WheadonH,TrindadeM,NicholsJ,KajiK,EnverTandBragançaJ–“AcutelossofCited2impairsNanogexpressionanddescreasesself-renewalofmouseembryonicstemcells”–StemCells,33,699-712(2015).

Mena-BarragánT,NaritaA,MatiasD,TiscorniaG,NanbaE,OhnoK, SuzukiY,HigakiK,GarciaFernández JM,OrtizMelletC.pH-ResponsivePharmacologicalChaperones forRescuingMutantGlycosidases. Angew Chem Int Ed Engl. 2015 Sep 28; 54(40):11696-700. doi:10.1002/anie.201505147.

Adriana Guerreiro, Custódia Gago, M. Leonor Faleiro, Maria Miguel and Maria D C Antunes.Raspberry fresh fruit quality as affectedbypectin-and alginate-based edible coatings enrichedwithessentialoils.ScientiaHorticulturae(2015)194:138-146.

C. Tefiani, A. Riazi, F. Youcefi, S. Aazza, C. Gago, M.L. Faleiro, L.G. Pedro, J.G. Barroso, A.C.Figueiredo, C. Megías, I. Cortés-Giraldo, J. Vioque and M.G. Miguel. Journal of Essential OilResearch(2015)27,2,131-139.

AdrianaC.Guerreiro,CustódiaM.L.Gago,MariaL.Faleiro,MariaG.C.Miguel,MariaD.C.Antunes.Theeffectofalginate-basedediblecoatingsenrichedwithessentialoilsconstituentsonArbutusunedoL.freshfruitstorage.PostharvestBiologyandTechnology(2015),100,226-233.

AdrianaC.Guerreiro,CustódiaM.L.Gago,MariaL.Faleiro,MariaG.C.Miguel,MariaD.C.Antunes.Theuseofpolysaccharide-basedediblecoatingsenrichedwithessentialoilstoimproveshelf-lifeofstrawberries.PostharvestBiologyandTechnology(2015),110,51-60.

Melo, J., Andrew, P.W. Faleiro, M.L. (2015) Listeria monocytogenes in cheese and the dairyenvironment remains a food safety challenge: the role of stress responses. Food ResearchInternational67:75-90.

Santos AI, Martinez-Ruiz A, Araújo IM (2015) S-nitrosation and neuronal plasticity. BritishJournalofPharmacology172(6):1468-1478.

Machado VM,MorteMI, Carreira BP, AzevedoMM, Takano J, Iwata N, Saido TC, Asmussen H,Horwitz A, Carvalho CM, Araújo IM (2015) Involvement of calpains in adult neurogenesis:implicationsforstroke.FrontiersinCellularNeuroscience.9:22.

Filipe Pinto, Nathalia C Campanella, Lucas F Abrahão-Machado, Cristovam Scapulatempo-Neto,AntonioTdeOliveira,Maria JBrito,RaquelPAndrade,DenisePGuimarães,RuiMReis.2015.TheembryonicBrachyurytranscriptionfactor isanovelbiomarkerofGISTaggressivenessandpoorsurvival.GastricCancer[Epubaheadofprint]doi:10.1007/s10120-015-0505-0.

AnaluceGouveia,HugoM.Marcelino, LisaGonçalves, Isabel PalmeirimandRaquel P.Andrade.2015. Patterning in Time and Space: HoxB Cluster Gene Expression in the Developing ChickEmbryo.CellCycle14:135-45.

MartinhoR.G. , Guilgur L., PrudêncioP. (2015).Howgene expression in fast proliferating cellskeepspace.Bioessays.2015May;37(5):514-24.

Silva R. and Martinho R.G. . (2015). Developmental roles of Protein N-terminal acetylation.Proteomics,2015Jul;15(14):2402-9.doi:10.1002/pmic.201400631.

Monteiro,A.S., Freitas,R., Palmeirim, I.Genomicsof zebrafishhoxbaandhoxbb loci. JournalofAppliedIchthyology(2014)30(4),pp.689-695

Carreira BP, MorteMI, Santos AI, Lourenço AS, Ambrósio AF, Carvalho CM, Araújo IM (2014)Nitric oxide from inflammatory origin impairs neural stem cell proliferation by inhibitingepidermalgrowthfactorreceptorsignaling.FrontiersinCellularNeuroscience8:343.

SantosAI,CarreiraBP,NobreRJ,CarvalhoCM,AraújoIM(2014)Stimulationofneuralstemcellproliferationbyinhibitionofphosphodiesterase5.StemCellsInternational2014:878397.

PintoJP,KalathurRKR,MachadoRSR,XavierJM,BragançaJandFutschikME–“StemCellNet:aninteractive platform for network-oriented investigations in stem cell biology” - Nucleic AcidsRes.,2014,42(WebServerissue):W154-160.

Apolónio,J.,Faleiro,M.L.,Miguel,M.G.,Neto,L.(2014)NoinductionofantimicrobialresistanceinStaphylococcusaureusandListeriamonocytogenesduringcontinuousexposuretoeugenolandcitral.FEMSMicrobiologyLetters354:92-101.

GilCarraco,AnaN.Gonçalves,CarlosSerraandRaquelP.Andrade.2014.MicroRNAprocessingmachineryinthedevelopingchickembryo.GeneExprPatterns16:114–121.

Filipe Pinto, Nelma Pértega-Gomes, Márcia S Pereira, José R Vizcaíno, Pedro Monteiro, Rui MHenrique, Fátima Baltazar, Raquel P Andrade, Rui M Reis. 2014. T-box transcription factorBrachyuryisassociatedwithprostatecancerprogressionandaggressiveness.ClinCancerRes20:1–13.

Caroline J. Sheeba, Raquel P. Andrade and Isabel Palmeirim2. 2014. Limb patterning: fromsignalinggradientstomolecularoscillations.JMolBiol426:780-4.

Tatiana P. Resende, Raquel P. Andrade and Isabel Palmeirim. 2014. Timing embryosegmentation: dynamics and regulatory mechanisms of the vertebrate segmentation clock.BiomedResInt2014:718683.

Pereira P.A., Navarro-Costa P., Martinho R.G. and Becker J.D. (2014). Evolutionarily conservedmechanismsofmalegermlinedevelopmentinfloweringplantsandanimals.BiochemicalSocietyTransactions.42(2):377-82.

GuilgurL.,PrudêncioP.,SobralD.,LisekovaD.,RosaA.,MartinhoR.G.. (2014).Requirement forhighlyefficientpre-mRNAsplicingduringDrosophilaearlyembryonicdevelopment.eLIFE2014Apr22;3:e02181.

FerreiraT.,PrudêncioP.,MartinhoR.G.(2014).DrosophilaProteinKinaseN(Pkn)isanegativeregulatorofactin-myosinactivityduringoogenesis.Dev.Biol.2014

MariaG.Miguel,MariaL.Faleiro,AdrianaC.GuerreiroandMariaD.Antunes.ArbutusunedoL.:Chemical and Biological Properties. Molecules 2014, 19, 15799-15823;doi:10.3390/molecules191015799.

Abdelmalek Wiem, Aazza Smail, Mnif Wissem, Faleiro M, Miguel M. Antioxidant, anti-inflammatoryandantiacetylcholinesteraseactivitiesofleaf,flowerandseedaqueousextractsofLawsoniainermisfromTunisia.InternationalJournalofPharmacyandPharmaceuticalSciences(2014)6,445-452.

LuísaMota, A. Cristina Figueiredo, Luís G. Pedro., José G. Barroso,M. GraçaMiguel,M. LeonorFaleiro and Lia Ascensão. Volatile-Oils Composition, and Bioactivity of the Essential Oils of

Plectranthusbarbatus,P.neochilus,andP.ornatusGrowninPortugal.Chemistry&Biodiversity(2014)11,719–732.

Bookchapters

BragançaJ,Machado-OliveiraG,Pacheco-LeyvaI,MatiasAC–“Understandingcancerstemcellsbiologytogetridoftumours”–InternationalManualofOncologyPractice.(iMOP)-PrinciplesofMedicalOncology.deMelloRA,TavaresÁ,MountziosG(Eds.).SpringerInternationalPublishing.2015.Chapter2,p15-28.eBookISBN:978-3-319-21683-6.HardcoverISBN978-3-319-21682-9.

Araújo IM and Carvalho CM (2016) Sistemas auditivo e vestibular inNeurociências. Edited byLidel.Editors:AnaCristinaRego,CatarinaOliveiraandCarlosJorgeDuarte.

PaulaAgostinhoandAraújoIM(2016)GABAesinapsesGABAérgicasinNeurociências.EditedbyLidel.Editors:AnaCristinaRego,CatarinaOliveiraandCarlosJorgeDuarte.

COMPUTATIONAL&SYSTEMSBIOLOGYRESEARCHGROUPRG-4773-2802A-Structure&researchoverviewTheComputational& SystemsBiology (CSB) group integrates complementary expertise in thefieldsofcomputational,structuralandsystemsbiologyaswellasbioinformaticsandfunctionalgenomics. Its research topics range from themodellingofprotein structures to the analysis oflarge-scalemolecularnetworks. It leadsseveraldata-drivenresearchprojectsaswellasassistsother groups in the analysis andmanagement of omics data. The group is organized in threeresearchlaboratories:The Systems Biology & Bioinformatics Laboratory (www.sysbiolab.eu), led by Dr MatthiasFutschik, is active in the development of novel methods as well as software and databaseimplementationintheareaofsystemsbiology(e.g.,UnifiedHumanInteractome,www.unihi.org;HeartEXpress database, heartexpress.sysbiolab.eu). In addition, the SysBioLab has expertise inprocessingandanalysisofhighthroughputdata,havingcontributedseveralpopularRpackagesto the community-based Bioconductor project. Besides developing computational resources,their research is focused on deciphering and in silico reconstruction of molecular networksunderlyingseveralphysiologicalandpathophysiologicalprocesses.Thelabisactivelyinvolvedinthe study of various biological systems with strong relevance to medicine. Current projectsinclude network-based investigations into stem-cell differentiation, oncogenesis andneurodegeneration in close collaborationwith local experimentallyworking groups aswell aswithinternationalpartners.

TheinterestoftheFunctionalGenomicsofCancerLaboratory(maialab.org),ledbyProfessorDrAna Teresa Maia, is focused on studying the influence of cis-regulatory variants in cancersusceptibility and biology. Cisregulatory polymorphisms generate allelic imbalance in geneexpression throughout thehumangenomeandcontribute tophenotypicvariability in complextraits. The main aim of the laboratory is to apply this concept to the development of novelapproachestodetectbreastcancerpredisposition.Inaddition,thelaboratoryisinvestigatingtheroleof allelic imbalanceof gene expression in tumourbiology. For its research, the laboratorycombines the data generation (RNA-seq of clinical samples) with advanced bio-informaticsanalysis of publicly available RNA-seq and DNA-seq data from cancer cohorts and follow-upexperimentalvalidation.

TheBiomolecularSimulationLaboratory,ledbyProfessorDrPauloMartel,isactivelyengagedinthedevelopmentofmethodsforproteinsimulation,particularlyapproachestothecalculationofelectrostatics and proton/electron transfer systems and pH-dependent molecular dynamics.ImplementationandoptimizationofCandPythoncodes(forCPU’sandGPU’s)isalsounderway.ImportantapplicationsystemsincludetheCytochromeP450’s(catalyticmechanismanddockingofsmall ligands)andtheBPG/MGPfamilyofboneandcartilageproteins(stability,bindingandproteinevolution).B-Productivity2014-presentTheCSBGrouphaspublished20 scientific articlesand1bookchapter.During thisperiod, theworkoftheCSBgrouphasbeencited1300times(2300timessince2011;WebofScience).TheCSBgroupis fundedby1FCTFCT/DAADTransnationalcooperationgrant,2FCTPost-docFellowships,aMarieCurieCareerIntegrationGrant,andaMaratonadaSaúdePrize.Supervision:6Post-Doc,3PhDstudents,4MScstudents.Conferencesandexternalcommunications:organizedthreeeventsforresearchfundraisingandorganizedoneandparticipatedinanotherseveneventsforSciencedisseminationtothegeneralpublic.C-CollaborationsAnaTeresaMaiaExternal: Dr Nuno Barbosa Morais at Institute of Molecular Medicine (Lisbon) - 1 Post-Doc(basedatCBMR)co-supervisionProf Sir Bruce Ponder, Dr Suet-Feung Chin, Professor Carlos Caldas, Dr James Brenton, DrShamith Samarajiwa at University of Cambridge – 1 funded project, 2 papers published, 4manuscriptsinpreparation,1Post-Doc(basedatCBMR)co-supervisionProfRenéBernardsatNetherlandsCancerInstitute–1manuscriptinpreparationProfAdéleMurrellatUniversityofBath(U.K.)–oneongoingproject

Dr Benitlon Carvalho at University of Campinas (Brazil) – one ongoing project, co-supervise 1Post-DocBreastsurgeryteamatHospitalParticulardoAlgarveInternal:PedroCastelo-BrancoPauloMartelExternal:DrAntónioBaptistaat InstitutodeTecnologiaQuímicaeBiológica,NewUniversityofLisbonDrMariaR.FélixatUniversidadedeÉvoraProfDrLeonorCancelaatCCMAR,UniversidadedoAlgarveDrRitaCastilhoatCCMAR,UniversidadedoAlgarveDrLeonorCruzeiroatDepartmentofPhysics,UniversidadedoAlgarveMatthiasFutschikExternal:AgapiosSachinidisatUniversityofCologne(Germany)DrPauldeSousaatMRCforRegenerativeMedicine(Scotland)DrNunodosSantosati3S(Porto)Internal: Dr Gustavo Tiscórnia, Prof Dr Wolfgang Link, Prof Dr José Braganca, Prof Dr LenorFaleiro,ProfDrEduardoMeloD-Publications2014–presentBal G, Futschik ME, Hartl D, Ringel F, Kamhieh-Milz J, Sterzer V, Hoheisel JD, Alhamdani MS,SalamaA.(2016)Identificationofnovelbiomarkersinchronicimmunethrombocytopenia(ITP)by microarray-based serum protein profiling. Br J Haematol. 172(4):602-15. doi:10.1111/bjh.13861.

Giner-Lamia J, Pereira SB, Bovea-Marco M, Futschik ME, Tamagnini P, Oliveira P. (2016)Extracellular Proteins: Novel Key Components of Metal Resistance in Cyanobacteria? FrontMicrobiol.7:878.doi:10.3389/fmicb.2016.00878.

Hernández-PrietoMA,SemeniukTA,FutschikME.(2014)Towardasystems-levelunderstandingof gene regulatory, protein interaction, andmetabolic networks in cyanobacteria. FrontGenet.5:191.doi:10.3389/fgene.2014.00191.

Hernández-Prieto MA, Semeniuk TA, Giner-Lamia J, Futschik ME. (2016) The TranscriptionalLandscape of the Photosynthetic Model Cyanobacterium Synechocystis sp. PCC6803. Sci Rep.6:22168.doi:10.1038/srep22168.

HillR,KalathurRK,CallejasS,ColaçoL,BrandãoR,SereldeB,CebriáA,Blanco-AparicioC,PastorJ,FutschikM,DopazoA,LinkW. (2014)Anovelphosphatidylinositol3-kinase(PI3K) inhibitordirectsapotentFOXO-dependent,p53-independentcellcyclearrestphenotypecharacterizedbythedifferentialinductionofasubsetofFOXO-regulatedgenes.BreastCancerRes.16(6):482.doi:10.1186/s13058-014-0482-y.

HillR,KalathurRK,ColaçoL,BrandãoR,UgurelS,FutschikM,LinkW.TRIB2asabiomarkerfordiagnosis and progression of melanoma. Carcinogenesis. 36(4):469-77. doi:10.1093/carcin/bgv002

KalathurRK,Giner-LamiaJ,MachadoS,BarataT,AyasollaKR,FutschikME.TheunfoldedproteinresponseanditspotentialroleinHuntington'sdiseaseelucidatedbyasystemsbiologyapproach.Version 2. F1000Res. 2015 May 1 [revised 2016 Mar 2];4:103. doi:10.12688/f1000research.6358.2.

KalathurRK,PintoJP,Hernández-PrietoMA,MachadoRS,AlmeidaD,ChaurasiaG,FutschikME.(2014)UniHI7:anenhanceddatabaseforretrievalandinteractiveanalysisofhumanmolecularinteraction networks. Nucleic Acids Res. 42(Database issue):D408-14. doi:10.1093/nar/gkt1100.

Kamhieh-Milz J, Moftah RF, Bal G, Futschik M, Sterzer V, Khorramshahi O, BurowM, Thiel G,StukeSontheimer A, Chaoui R, Kamhieh-Milz S, Salama A. (2014) Differentially expressed

microRNAs in maternal plasma for the noninvasive prenatal diagnosis of Down syndrome(trisomy21).BiomedResInt.2014;2014:402475.doi:10.1155/2014/402475.

Marques CL, Fernández I, Viegas MN, Cox CJ, Martel P, Rosa J, Cancela ML, Laizé V. (2016)Comparative analysis of zebrafish bone morphogenetic proteins 2, 4 and 16: molecular andevolutionaryperspectives.CellMolLifeSci.73(4):841-57.doi:10.1007/s00018-015-2024-x.

Pells S, Koutsouraki E,Morfopoulou S, Valencia-Cadavid S, Tomlinson SR, KalathurR, FutschikME,DeSousaPA.(2015)NovelHumanEmbryonicStemCellRegulatorsIdentifiedbyConservedand Distinct CpG Island Methylation State. PLoS One. 10(7):e0131102. doi:10.1371/journal.pone.0131102.

PeterlongoP,Chang-Claude J,MoysichKB,RudolphA, SchmutzlerRK, Simard J, SoucyP,EelesRA, Easton DF, Hamann U, Wilkening S, Chen B, Rookus MA, Schmidt MK, van der Baan FH,SpurdleAB,WalkerLC,LoseF,MaiaAT,etal.(2015)CandidategeneticmodifiersforbreastandovariancancerriskinBRCA1andBRCA2mutationcarriers.CancerEpidemiolBiomarkersPrev.24(1):308-16.doi:10.1158/1055-9965.EPI-14-0532

PintoJP,KalathurRK,OliveiraDV,BarataT,MachadoRS,MachadoS,Pacheco-LeyvaI,DuarteI,FutschikME.(2015)StemChecker:aweb-basedtooltodiscoverandexplorestemnesssignaturesingenesets.NucleicAcidsRes.43(W1):W72-7.doi:10.1093/nar/gkv529.

PintoJP,MachadoRS,XavierJM,FutschikME.Targetingmolecularnetworksfordrugresearch.FrontGenet.5:160.doi:10.3389/fgene.2014.00160.

Pinto JP, Reddy Kalathur RK, Machado RS, Xavier JM, Bragança J, Futschik ME. (2014)StemCellNet: an interactive platform for network-oriented investigations in stem cell biology.NucleicAcidsRes.42(WebServerissue):W154-60.doi:10.1093/nar/gku455.

SilvaG,LimaFP,MartelP,CastilhoR.(2014)ThermaladaptationandclinalmitochondrialDNAvariation of European anchovy. Proc Biol Sci. 281(1792). pii: 20141093. doi:10.1098/rspb.2014.1093.

StroedickeM,BounabY,StrempelN,KlockmeierK,YigitS,FriedrichRP,ChaurasiaG,LiS,HesseF, Riechers SP, Russ J, Nicoletti C, Boeddrich A,Wiglenda T, Haenig C, Schnoegl S, Fournier D,GrahamRK,HaydenMR,SigristS,BatesGP,PrillerJ,Andrade-NavarroMA,FutschikME,WankerEE. (2015) Systematic interaction network filtering identifies CRMP1 as a novel suppressor ofhuntingtin misfolding and neurotoxicity. Genome Res. 25(5):701-13. doi:10.1101/gr.182444.114.

Varanda CM, MachadoM, Martel P, Nolasco G, ClaraMI, Félix MR. (2015) Correction: GeneticDiversityoftheCoatProteinofOliveMildMosaicVirus(OMMV)andTobaccoNecrosisVirusD(TNV-D) Isolates and Its Structural Implications. PLoS One. 10(5):e0128171. doi:10.1371/journal.pone.0128171.

VarandaCM,MachadoM,MartelP,NolascoG,ClaraMI,FélixMR.(2014)GeneticdiversityofthecoatproteinofOlivemildmosaicvirus(OMMV)andTobacconecrosisvirusD(TNV-D)isolatesanditsstructuralimplications.PLoSOne.9(10):e110941.doi:10.1371/journal.pone.0110941.

Vollan HK, Rueda OM, Chin SF, Curtis C, Turashvili G, Shah S, Lingjærde OC, Yuan Y, Ng CK,DunningMJ,DicksE,ProvenzanoE, SammutS,McKinneyS,Ellis IO,Pinder S, PurushothamA,Murphy LC, Kristensen VN; METABRIC Group, Brenton JD, Pharoah PD, Børresen-Dale AL,AparicioS,CaldasC.(2015)AtumorDNAcomplexaberrationindexisanindependentpredictorof survival in breast and ovarian cancer. Mol Oncol. 9(1):115-27. doi:10.1016/j.molonc.2014.07.019.

MOLECULARBIOMEDICINERESEARCHGROUPRG-4773-1223A-Structure&researchoverviewTheMolecularBiomedicine(MB)ResearchGroupincorporatestheactivitiesoffivelaboratories:ProteinBiochemistry andBiophysics, DrugDelivery,Molecular Energetics, Biomembranes andPharmacogenomicandMolecularToxicology.All the five laboratoriesstudybiomolecules, theirstructure,functionandorganizationfromabiomedicalperspectiveandaimtoaddressmolecularorganizationandmechanismsinvolvedinprocessesrelevantinthebiomedicalfield.1. The Protein Biochemistry andBiophysics (PBB) lab headed by ProfessorDr Eduardo PinhoMelousesbiochemistryandbiophysicstoolstostudyproteinswithemphasisonthemechanismsinvolvedonproteinmisfoldingandcelltoxicityassociatedwiththis.Proteinstability,foldinganddisulphidebondformationaswellasproteinaggregationanditsrelationtoneurodegenerativediseasesaremainfociofresearch.Currentresearchprojectsinclude:(i)mechanismunderlyingpriondiseases, (ii)mechanismsof disulphidebond formationon secretoryproteins and redoxpoise in the endoplasmic reticulum (in collaboration with David Ron from the CambridgeUniversity), (iii) structure-function relationships of multi-copper oxidases (collaboration withLígiaMartinsfromITQB,Oeiras)and(iv)effectoffreezingontherapeuticproteins(collaborationwithMiguelRodriguesfromIST,Lisbon).2.TheDrugDelivery(DD)labheadedbyProfessorDrAnaGrenhadevelopsparticulatecarriers,mostly based on carbohydrates, for drug delivery. Polymeric based drug delivery systems andtheefficacyofthelungrouteintherapeuticsarecurrentlyunderfocus.Currentresearchprojectsinclude: (i) exploitation of polysaccharide properties in drug delivery, (ii) development ofpolysaccharide-basednano-andmicroparticlesfordrugdeliveryapplicationswithemphasisonlungdeliveryand(iii)designoftoolstoimprovetheinvitroevaluationofdrugdeliverysystems.3. The Molecular Energetics (ME) lab headed by Professor Dr Rui Borges uses mainlycalorimetrictechniquestoinvestigatethestructure,energeticsandreactivityof(bio)molecules.Current research projects include: (i) application of photoacustic calorimetry (PAC) to smallmolecules and to biodiesel from microalgae biomass and (ii) development of a prototypecombiningaquartzcrystalmicrobalancewithaheatconductioncalorimeter(QCMHCC)tostudybiomolecularinteractions.4. The Biomembranes (BM) lab headed by Professor Dr Jorge Martins studies the structure,kinetics, dynamics and organization of lipid bilayers and their soulability properties. Currentresearchprojectsinclude:(i)effectofcholesterolonthestructure,organization,andpolarityoflipidbilayersand(ii)fluorescenceanisotropyoftheprobeDPHinmodelmembranesdisplayinglateralheterogeneity.5. The Pharmacogenomic and Molecular Toxicology (PMT) lab headed by Professor Dr VeraRibeiro is devoted to the study of drugmetabolismandmechanismsof cell toxicity and inter-individual variability in response to chemicals. Current research projects include: (i)identification of pharmacogenomic markers associated to responses in therapies for cancer,infectiousandcardiovasculardiseasesand(ii)crosstalkbetweenregulationofdrugmetabolismandchangesincellhomeostasis.B–Productivity2014-presentAtotalof26papershavebeenpublishedsince2014.The5membersoftheMBgroupwerecited∼900timesduringthelasttwoyearsandahalfandhavesupervised1post-doctoralstudent,4PhD, 12Master and 6 undergraduate students. Around 600 k€ from the Portuguese scientificresearchcouncilFCThavefundedtheactivitiessince2011/12butcurrentlynofundedprojectisrunning.C-Publications2014-presentBrissos,V.,N.Gonçalves,E.P.Melo,L.O.Martins(2014)PLOSOne9:e87209.

Martins,J.(2014)Biochim.Biophys.ActaBioenergetics1837(Supl):e29-e29.

Nunes,R., SRodrigues,PPasko,MTyszka–Czochara,AGrenha, I SaraivadeCarvalho, (2014)IndustrialCropsandProducts52,99-104.

Perestrelo,AR,AGrenha,AMRosadaCosta,JABelo(2014)MaterialsScienceandEngineeringC:MaterialsforBiologicalApplications40,336-344.

Tavares,E.,J.A.Macedo,P.M.R.Paulo,C.Tavares,C.Lopes,E.P.Melo(2014)Biochim.Biophys.Acta–MolecularBasisofDisease1842:981-991.

Tsunoda,S.,E.Avezov,A.Zyryanova,T.Konno,L.Mendes-Silva,E.P.Melo,H.P.Harding,D.Ron(2014)eLife3:e03421.

Agapito,F.;Santos,R.C.;BorgesdosSantos,R.M.;MartinhoSimões,J.A.(2015)J.Phys.Chem.A,119,2998-3007.

Avezov,E.,T.Konno,A.Zyryanova,W.Chen,R.Laine,A.Crespillo-Casada,E.P.Melo,R.Ushioda,K.Nagata,C.F.Kaminski,H.P.Harding,D.Ron(2015)BMCBiology13:2.

Butenko,N,Pinheiro, JP, Silva,JP,Tomaz,AI,Correia,I,Ribeiro,V,Pessoa, JC,Cavaco, I. (2015) JInorgBiochem.147,165-176.

Carvalho, CP, Norouzy, A, Ribeiro,V, Nau, WM, Pischel, U. (2015) Organic & BiomolecularChemistry13,2866-2869.

Correia,JC,Massart,J,deBoer,JF,Porsmyr-Palmertz,M,Martínez-Redondo,V,Agudelo,LZ,Sinha,I,Meierhofer, D, Ribeiro, V, Björnholm, V, Sauer, S, Dahlman-Wright, K, Zierath, JR, Groen, AK,Ruas,JL.,(2015)MolMetab4,891-902.

Dantuma,D,RElmaddawi,YPathak,AGrenha,RdeOliveira, CPaludo,MAdosSantos (2015)AmericanJournalofMedicalandBiomedicalResearch3,102-106.

Ebadzad,G.,C.Medeira,I.Maia,J.MartinsandA.Cravador(2015)Eur.J.PlantPathol.143,705-723.

Estrela,N.,H.G.Franquelim,C.Lopes,E.Tavares,J.A.Macedo,G.Christiansen,D.E.Otzen,E.P.Melo(2015)Proteins83:2039-2051.

Grenha,A(2015)CurrentPharmaceuticalDesign21,4773-4774.

Konno,K.,E.P.Melo,C.Lopes,C.F.Kaminski,I.Mehmeti,S.Lenzen,D.Ron,E.Avezov(2015)J.CellBiol.211:253-259.

Martins do Canto, A.M.T., P. D. Santos, J. Martins and M. S. Loura (2015) Colloids Surf. A:Physicochem.Eng.Aspects480,296-306.

Mouffouk,F,T.Simão,D.Dornelles,A.D.Lopes,P.Sau,J.Martins,K.M.Abu-Salah,S.A.Alrokayan,A.M.R.daCostaandN.R.dosSantos(2015)Int.J.Nanomed.10,1-14.

Rodrigues, S, C Cordeiro, B Seijo, CRemuñánLópez, AGrenha (2015) Carbohydrate Polymers.123,369-380.

Rodrigues,S,AGrenha,(2015)CurrentPharmaceuticalDesign21,4869-4887

Rodrigues,S,LCardoso,AMRosadaCosta,AGrenha,(2015)Materials8,5647-5670

Santos, MA, A Grenha (2015) Polysaccharide nanoparticles for protein and peptide delivery:exploringlessknownmaterials.In:RDonev(Ed.)AdvancesinProteinChemistryandStructuralBiology.Vol.98,Burlington:AcademicPress,pp.223-261

AM Rosa da Costa, AM, M Dionísio, L Braz, M Corvo, JP Lourenço, A Grenha, (2016) Chargedpullulan derivatives for the development of nanocarriers by polyelectrolyte complexation.InternationalJournalofBiologicalMacromolecules.86:129-138.

Cunha,L,AGrenha, (2016)Sulphated seaweedpolysaccharidesasmultifunctionalmaterials indrugdeliveryapplications.MarineDrugs,14(3),42.

Alves,AD, JS Cavaco, FGuerreiro, JP Lourenço,, AMRosadaCosta,AGrenha, (2016) Inhalableantituberculartherapymediatedbylocustbeangummicroparticles.Molecules,21,702:pages1-22.

Gangadhar,K.N.;Pereira,H.;Diogo,H.P.;BorgesdosSantos,R.M.;Devi,B.L.A.P.;Prasad,R.B.N.;Custódio,L.;Malcata,F.X.;Varela, J.;Barreira,L. (2016)Assessmentandcomparisonof theproperties of biodiesel synthesized from three different wet microalgae biomass. J. AppliedPhycology28,1571-1578.

ONCOBIOLOGYRESEARCHGROUPRG-4773-1395A-StructureofthegroupTheOncobiologyresearchgroupisconstitutefourlaboratorieswithresearchinterestscoveringseveralaspectsofcancerresearch:TheCancerSignallingLaboratory(ProfDrWolfgangLink)investigatesandmanipulatesproteintranslocation to treatcancer.Aberrant localizationof tumorsuppressorproteinssuchasFOXOfactorshasbeenproposedtobeanimportantmechanismfortheirinactivationinhumancancer.Hence, the therapeutic restoration of normal protein location has achieved considerableattention.Usingacombinationofchemicalgeneticsandhighcontentroboticmicroscopy,ourlabhasidentifiedseveralmeanstorestoretumorsuppressors, includingFOXO, incancercells.Theresearch seeks todeterminehow the tumor suppressorFOXO influences tumor formationandprogression as well as resistance to anticancer treatment, and to advance the previouslyidentifiednoveltherapeutic/diagnostictargetsanddrugcandidatesintoclinicaldevelopment.TheCancerBiologyandProgressionLaboratory(DrPatriciaMadureira)focusonunderstandinghow cancer cells modulate cellular systems to survive, proliferate, invade and metastasize.Cancer cells typically havehigher levels of reactive oxygen species (ROS) compared tonormalcells, leading to elevated ROS-dependent signalling that activate survival, proliferation andmetastaticcascades.However,excessiveROScaninduceDNA,lipidandproteindamageleadingto cell death. For this reason cancer cells upregulate ROS scavenging proteins to avoid ROStoxicity.Theresearchinvestigatetheroleplayedbyantioxidantproteins,particularlyannexinA2in the regulation of ROS-dependent signalling pathways, and the role of the annexin A2heterotetramer intheregulationofplasminactivity that isassociatedwithcancercell invasionandmetastasis.TheCellCycleandCancerBiologyLaboratory(ProfDrÁlvaroTavares)examinesthecomponentsand regulatory mechanisms of the mitotic machinery, and explore mechanisms by whichproblems in cell division can lead to cancer. Twodifferent aspects ofmitosis are in focus: thechromosome attachment to the spindle (by analysing the kinetochore function) and thecompletionofcelldivision(bystudyinggenes involved in theexecutionofcytokinesis).TakingadvantageofDrosophilageneticsandhumanculturedcells,wehaveidentifiedasetofnewgenesthat when mutated result in chromosome miss-aggregation, spindle assembly defects andabscissionfailure.SomeofthesegenescausetumorformationinDrosophilaandourmaingoalistofindoutwhethertheyareequallyinvolvedinhumantumorigenesis.The Telomere Maintenance Laboratory (Prof Dr Pedro Castelo-Branco) is interested inunderstanding howmost cancers are able to recur by achieving unbounded self-renewal. Thishallmark of cancer is governed by telomere maintenance and results from constitutivetelomerase activation through TERT expression at the molecular level. At the cellular levellimitlessself-renewalcanbeexplainedbytheexistenceofCancerStemCells.The four research labs use complementary approaches to address key questions in cancerresearchwithongoing collaborations.The grouporganizes regularmeetings to share researchdataandfostercollaborations.TheResearchGroupcoordinatorcallsmeetingstwiceayearwiththe lab heads to discuss strategic decisions including organization, funding and scientificobjectives.B-ResearchoverviewTheoverallobjectivesof theTelomeremaintenancelaboratory (TML)aretodevelopaplatformthatcandelivertherapeuticagentsspecificallytotheCSCtumorsub-populationandtoexplorethepotential diagnostic andprognostic valueof epigenetic cancerbiomarkers inorder tohelpdesigningtherapeuticapproachesinaneraofpersonalizedmedicine.Determiningthemoleculareventsleadingtomalignantcelltransformation.Malignanttransformationisastepwiseprocessinvolvingtheacquisitionofmultiplegeneticandepigenetic alterations. Our aim is to discover which and how these events lead to thederegulationofessentialprocessessuchascelldivision.Decipheringtheregulatoryeventsthat

drivemalignanttransformationrepresentsamajorchallengeforbiology.Ourresearchprogramextendsfrombasicstudiesincellbiologyandsignallingtopre-clinicalandclinicalstudies.WiththesegoalsinmindwearedeterminingthemoleculareventsthatoccurafterinactivationoftheMob genes that conduce to cells transformation, in particular cell polarity changes, usingDrosophila mutants and human cultured cells; determining the kinetochore substrates of thekinase Plk1, and how their (lack of) phosphorylation affects chromosome segregation duringmitosis;andweareusingaCALIapproachtodeterminetherequirementofbothMob1andPlk1proteinsinthemid-bodytopromoteabscission.UnderstandingthemoleculardeterminantsofcancerinvasionandmetastasisUnderstanding themolecularmechanismsbywhich cancer cells invadeandmetastasizemightprovide crucial tools for the development of novel therapies targeted at blocking the majorcontributor to cancer patient death. To this end theOncobiology group aims to study the roleplayedbyproteins(e.g.,thechemokinereceptorCCR7andtheplasminogenreceptorannexinA2hetero-tetramer) inthe invasiveandmetastaticcapabilityofcancercells.Usingknockdownforgenes of interest in cancer cell lines, we will determine the contribution of the respectiveproteins to cancer cell invasion in vitro, bymatrix-gel assays and their contribution to tumorgrowth,angiogenesisandmetastasisinvivobyusingxenograftmodels.Identificationoftherapeutictargets,drugcandidatesandcompaniondiagnosticsThefutureofcancertherapyreliesonunderstandingofthemolecularandgeneticabnormalitiesthat drive cancers, on a rich pipeline of compounds targeting such lesions, and on theappropriate use of companion diagnostics to pre-screen patients that are likely to respond.Therefore,weaimtoestablishthekinaselikeproteinTRIB2whichwehavecharacterizedtobeanoncogenicFOXOrepressorasacompaniondiagnostictooltopredictdrugresistance;identifyandvalidatenoveltargetsfortherapeuticinterventioninbothcancerandstromalcells,includingnovel FOXO repressor proteins and lymphotoxin signalling inhibitors; test our FOXO activatorcollectionofsmallmolecules(about300smallmoleculecompounds)foreffectsonlifespanandaging phenotypes in C. elegans; discover and characterize novel small molecule inhibitors ofFOXOproteinsandannexinA2.Relapseisstillthemajorcauseofcancerdeath.Most cancers are able to recur by gaining limitless selfrenewal. This hallmark of cancer isgovernedbytelomeremaintenanceandresultsfromconstitutivetelomeraseactivationthroughTERT expression at the molecular level. At the cellular level limitless self renewal can beexplained by the existence of Cancer Stem Cells. The overall objectives of the Telomeremaintenance laboratory (TML) are to develop a platform that can deliver therapeutic agentsspecifically to the CSC tumor sub-population and to explore the potential diagnostic andprognosticvalueofanepigeneticcancerbiomarkerthatwehaverecentlydescribedinordertohelpdesigningtherapeuticapproachesinaneraofpersonalizedmedicineC-Productivity2014-presentSince2014theOncobiologygrouppublished26articles,1bookchaptersandreceivedover1200citations(2363since2011;WebofScience)

D-Funding

E-National&internationalcollaborationsOnlycollaborationsreflectedincommonpublicationsarementionedCollaborator,Institution,CountryEndreKiss-TothUniversityofSheffieldUnitedKingdomGordonLithgowBuckInstituteforUSGuntherKauselmannTaconicArtemisGmbHGermanyJamesLorensUniversityofBergenNorwayMauricioBottaUniversityofSiennaItalyJoaquinPastorCNIO,MadridSpainBastienCautainFundaciónMEDINA,SpainFranciscaVicenteFundaciónMEDINA,SpainAliGureBilkentUniv.AnkaraTurkeyAnaDopazoCNIC,MadridSpainSelmaUgurelHautklinik,EssenGermanyRichardHillUniversityofPortsmouthUnitedKingdomDavidWaisman,DalhousieUniversity,HalifaxCanadaPatrickLeeDalhousieUniversity,HalifaxCanadaRamonMelloUAlg,FaroPortugalE-Publications2014-presentTrinquandA,Dos SantosNR,TranQuangC,Rocchetti F, ZaniboniB,BelhocineM,DaCostadeJesusC,LhermitteL,TesioM,DussiotM,CossetFL,VerhoeyenE,PflumioF,IfrahN,DombretH,Spicuglia S, Chatenoud L, Gross DA, Hermine O, Macintyre E, Ghysdael J, Asnafi V (2016).Triggering the TCR Developmental Checkpoint Activates a Therapeutically Targetable TumorSuppressive Pathway in T-cell Leukemia. Cancer Discov. 2016 Sep;6(9):972-85. doi:10.1158/2159-8290.

AguiarPN Jr,MunizTP,MirandaRR,TadokoroH, ForonesNM,Monteiro ID,Castelo-BrancoP,Janjigian YY, Mello RA. (2016) Current advances in targeted therapies for metastatic gastriccancer:improvingpatientcare.FutureOncol.Mar;12(6):839-54.doi:10.2217/fon.15.348.

ErnstA,JonesDT,MaassKK,RodeA,DeegKI,JebarajBM,KorshunovA,HovestadtV,TainskyMA,Pajtler KW, Bender S, Brabetz S, Gröbner S, Kool M, Devens F, Edelmann J, Zhang C, Castelo-BrancoP,TaboriU,MalkinD,RippeK,StilgenbauerS,PfisterSM,ZapatkaM,LichterP.(2016).Telomere dysfunction and chromothripsis. Int J Cancer. 2016 Jun 15;138(12):2905-14. doi:10.1002/ijc.30033.

Florindo,C,FerreiraBI,SerrãoSM,Tavares,AA,HillR,andLinkW(2016).Subcellularproteinlocalization in health and disease. eLS. John Wiley & Sons, Ltd: Chichester DOI:10.1002/9780470015902.a0026534

MadureiraPA,BharadwajAG,BydounM,GarantK,O'ConnellP,LeeP,WaismanDM.(2016)CellsurfaceproteaseactivationduringRAStransformation:Criticalroleoftheplasminogenreceptor,S100A10.Oncotarget.doi:10.18632/oncotarget.10279

Castaldo SA, Freitas JR, Conchinha NV, Madureira PA. (2015) The Tumorigenic Roles of theCellularREDOXRegulatorySystems.OxidMedCellLongevdoi:10.1155/2016/8413032

CastellarnauM.,ZanuyM.,CortésR.,Tarragó-CeladaJ.,FanT.W.,LinkW.andCascanteM.(2015)FOXO3amediatestheantitumoureffectsofmethylseleninicacid.PharmacolRes.102,218-234.

CautienB.,dePedroN.,ReyesF.andLinkW.(2015)Image-basedIdentificationofNuclearExportInhibitorsfromNaturalProducts.MethodsinMolecularBiology1270:307-19.doi:10.1007/978-1-4939-2309-0_22

Cautien B., Hill R., de Pedro N. and Link W. (2015). Components and regulation of nucleartransport processes. FEBS J. 282, 445-462. This article is accompanied by a podcast(http://www.yadayada.co.uk/Blackwell/PAI/Audio/Wolfgang_Jan2015.mp3)

FerreiraBI,HillR,andLinkW.(2015)Caughtinthecrosshairs;targeteddrugsandpersonalizedmedicine.CancerJ.21,441-447.doi:10.1097/PPO.0000000000000161.

HillR.,KalathurR.,ColaçoL.,BrandãoR.,UgurelS.,FutschikM.andLinkW.(2015)TRIB2asabiomarkerfordiagnosisandprogressionofmelanoma.Carcinogenesis36,469-477

LinkW.(2015).Tribblesbreakingbad:TRIB2suppressesFOXOandactsasanoncogenicproteininmelanoma.BiochemicalSocietyTransactions43,1085-1088;DOI:10.1042/BST20150102

Link W. (2015) Molecular Inhibitors in Targeted Therapy. Molecular inhibitors in targetedtherapy.Volume1,Issue1,ISSN(Online)2300-3650,DOI:10.1515/motth-2015-0001

MartinsR.,LithgowG.J.,LinkW.(2015)LongliveFOXO:UnravellingtheroleofFOXOproteinsinagingandlongevity.AgingCell15,196-207.doi:10.1111/acel.12427.

MatthewMistry,NataliyaZhukova,DanieleMerico,PatriciaRakopoulos,RahulKrishnatry,MaryShago, JimStavropoulos,NoaAlon, JasonPole,PeterN.Ray,VilmaNavickiene, JoshuaMangerel,MarcRemke, PawelBuczkowicz, VijayRamaswamy,Martin Li, TedYoung, Cindy Zhang, PedroCastelo-Branco,DouaBakry,SuzzaneLaughlin,AdamShlien,JenniferChan,KeithL.Ligon,JamesT. Rutka, Peter B. Dirks, Michael D.Taylor, Mark Greenberg, David Malkin, Annie Huang, EricBouffet,CynthiaE.HawkinsandUriTabori.(2015)BRAFmutationandCDKN2Adeletiondefineaclinicallydistinctsubgroupofchildhoodsecondaryhighgradeglioma(2015).JournalofClinicalOncology,33(9):1015-22.doi:10.1200/JCO.2014.58.3922.

SilvaPM,TavaresÁA,BousbaaH.(2015).Co-silencingofhumanBub3anddyneinhighlightsanantagonistic relationship in regulating kinetochore-microtubule attachments. FEBS Lett.589(23):3588-94

BarszczykM,BuczkowiczP,Castelo-BrancoP,MackSC,RamaswamyV,MangerelJ,AgnihotriS,RemkeM,GolbournB,PajovicS,ElizabethC,YuM,LuuB,MorrisonA,AdamskiJ,Nethery-BrokxK,LiXN,VanMeterT,DirksPB,RutkaJT,TaylorMD,TaboriU,HawkinsC.(2014).Telomeraseinhibition abolishes the tumorigenicity of pediatric ependymoma tumor-initiating cells. ActaNeuropathol.

Buczkowicz, Pawel, Christine Hoeman, Patricia Rakopoulos, Sanja Pajovic, Louis Letourneau,MiskoDzamba,AndrewMorrison,PeterLewis,EricBouffet,UteBartels,JenniferZuccaro,SameerAgnihotri, Scott Ryall, Mark Barszczyk, Yevgen Chornenkyy, Mathieu Bourgey, GuillaumeBourque, AlexandreMontpetit, Francisco Cordero, Pedro Castelo-Branco, JoshuaMangerel, UriTabori, Polly K.C. Ho, Annie Huang, Kathryn R. Taylor, Alan Mackay, Anne E Bendel, JavadNazarian, JasonRFangusaro,MatthiasKarajannis,DavidZagzag,NicholasK.Foreman,AndrewDonson, Julia V. Hegert, Amy Smith, Jennifer Chan, Lucy Lafay-Cousin, Sandra Dunn, JulietteHukin, ChrisDunham,Katrin Scheinemann, JeanMichaud, Shayna Zelcer, DavidRamsay, JasonCain,CameronBrennan,MarkM.Souweidane,Chris Jones,C.DavidAllis,MichaelBrudno,OrenBecher, Cynthia Hawkins (2014). Comprehensive genomic analysis of diffuse intrinsic pontinegliomasunravelsthreemolecularsubgroupsandanovelcancerdriver.NatureGenetics46:451-6.doi:10.1038/ng.2936.

CastilloCorrea,F.J.,DePedro,N.,RodriguezQuesada,L.,OvesCostales,D.,Tormo,J.R.,Martin,J.,Reyes, F., Genilloud,O. ,Vicente, F. ,Link,W. ,Cautain,B. (2014).Discoveryof novel inhibitor ofFOXOnuclearcytoplasmicshuttlingfromnaturalproductsofmarineorigin.EuropeanJournalofCancer,50,24.

CautienB., de PedroN.MuñozdeEscalonaM., GonzálezMenéndezV., Tormo J.R.,Martin J., ElAouadN.,ReyesF.,AsensioF.,GenilloudO.,VicentePérezF. andLinkW. (2014).High-contentscreening of natural products reveals novel nuclear export inhibitors. Journal of BiomolecularScreening19,57-65.

CortésR.,TarradoM.,TalancónD.,López,C.,LinkW.,DanielRuizD.,CentellesJ.J.,QuiranteeJ.andCascanteM. (2014) A novel cyclometallated Pt(II)-ferrocene complex induces nuclear FOXO3alocalization, apoptosis and synergizes with cisplatin to inhibit lung cancer cell proliferation.Metallomics6,622-633.

Hill R., CautienB., de PedroN. and LinkW. (2014). TargetingNucleocytoplasmic Transport inCancerTherapy.Oncotarget5,11-28.

HillR.,KalathurR.,CallejasS.,ColaçoL.,BrandãoR.,GarciaSereldeB.,CebriáA.,Blanco-AparicioC., Pastor J., FutschikM., Dopazo A. and LinkW. (2014) Gemonewide expression profiling inbreastcancerfollowingPhosphatidylinositol3-Kinase(PI3K)inhibitiondirectsp53-independentcellcyclearrestviathedifferentialinductionofFOXO-dependentgenes.BreastCancerResearch16,482.

Mack SC,WittH, PiroRM, Gu L, Zuyderduyn S, Stütz AM,Wang X, GalloM, Garzia L, ZayneK,ZhangX,RamaswamyV,JägerN,JonesDT,SillM,PughTJ,RyzhovaM,WaniKM,ShihDJ,HeadR,RemkeM,BaileySD,ZichnerT,FariaCC,BarszczykM,StarkS,Seker-CinH,HutterS, JohannP,BenderS,HovestadtV,TzaridisT,DubucAM,NorthcottPA,PeacockJ,BertrandKC,AgnihotriS,CavalliFM,ClarkeI,Nethery-BrokxK,CreasyCL,VermaSK,KosterJ,WuX,YaoY,MildeT,Sin-Chan P, Zuccaro J, Lau L, Pereira S, Castelo-Branco P, HirstM,MarraMA, Roberts SS, Fults D,Massimi L, Cho YJ, Van Meter T, GrajkowskaW, Lach B, Kulozik AE, von Deimling A, Witt O,Scherer SW,FanX,MuraszkoKM,KoolM,PomeroySL,GuptaN,Phillips J,HuangA,TaboriU,HawkinsC,MalkinD,KongkhamPN,WeissWA,JabadoN,RutkaJT,BouffetE,KorbelJO,LupienM,AldapeKD,BaderGD,EilsR,LichterP,DirksPB,PfisterSM,KorshunovA,TaylorMD.(2014).Epigenomic alterations define lethal CIMP-positive ependymomas of infancy.Nature 506, 445-50.doi:10.1038/nature13108.Epub2014Feb19.

MangerelJ,PriceA,Castelo-BrancoP,BrzezinskiJ,BuczkowiczP,RakopoulosP,MerinoD,BaskinB,Wasserman J, MistryM, BarszczykM, Picard D,Mack S, RemkeM, Starkman H,Elizabeth C,ZhangC,AlonN,LeesJ,AndrulisIL,WunderJS,JabadoN,JohnstonDL,RutkaJT,DirksPB,BouffetE, Taylor MD, Huang A, Malkin D, Hawkins C, Tabori U. (2014). Alternative lengthening oftelomeresisenrichedin,andimpactssurvivalofTP53mutantpediatricmalignantbraintumors.ActaNeuropathol.128(6):863-77.doi:10.1007/s00401-014-1327-6.

Mori M, Vignaroli G, Cau, Y,DiniJ, Hill R, Rossi M, Colecchia D,PešiM, LinkW, ChiarielloM,OttmannhC andBottaM. (2014)Discovery of 14-3-3protein-proteininteraction inhibitorsthatsensitizemultidrugresistantcancercells toDoxorubicinandtheAktinhibitorGSK690693.ChemMedChem9,973-983.

Silva PM, Reis RM, Bolanos-Garcia VM, Florindo C, Tavares ÁA, Bousbaa H. (2014) Dynein-dependenttransportofspindleassemblycheckpointproteins.FEBSLett.588:3265-3273.

ZhukovaN,RamaswamyV,RemkeM,MartinDC,Castelo-BrancoP,ZhangCH,FraserM,TseK,PoonR,ShihDJH,BaskinB,RayPN,BouffetE,DirksP,vonBuerenAO,PfaffE,KorshunovA,JonesDTW,NorthcottPA,KoolM,PughT,PomeroySL,ChoYJ,PietschT,GessiM,RutkowskiS,BognrL,ChoBK,EberhartCG,Fävre-MontangeM,FouladiM,FrenchPJ,GrajkowskaWA,GuptaN,HauserP, JabadoN, JouvetA, JungS,KimSK,KleknerA,KumabeT,LachB,Leonard JR36,LiauLM38,MassimiL,PollackIF,RaYS,RubinJB,VanMeirEG,WangKC,WeissWA,ZitterbartK,BristowR,AlmanB,HawkinsCE,MalkinD,CliffordSC,PfisterSM ,TaylorMDandTaboriU. (2014).WNTactivation by lithium abrogates TP53 mutation associated radiation resistance inmedulloblastoma (2014). Acta Neuropathol Communications, 24;2:174. doi: 10.1186/s40478-014-0174-y.

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COGNITIVENEUROSCIENCERESEARCHGROUPRG-4773-1394A-Structure&researchoverviewTheCognitiveNeuroscience(CNS)ResearchGroup,directedbyProfDrKarlMagnusPetersson,isan internationallywell-recognized researchunit focusedonquestions related to the functionalorganizationof thehumanbrain, cognition, andbehaviour.TheCNSgroupaddresses scientificissues related to language processing, learning & memory, reading & writing, developmentaldyslexia,aswellasobjectrecognition.Currently,most groupmembers (6/9) are senior researchers,who integrate cross-disciplinaryexpertise in neuroscience, cognitive & computational neuroscience, functional neuroimaging,cognitiveandexperimentalpsychology.TheCNSgrouphasestablishedandmanagesthestate-of-the-art laboratories for electrophysiological EEG/ERP research, behavioural and eye-trackingresearch (stationary high-resolution platform and amobile platform), aswell as data-analysisand computing facilities. Currently, on-going scientific projects relate to the neural basis ofmental processes and their behavioural manifestations, using state-of-the-art methods fromexperimental cognitive psychology, eye-tracking, and functional neuroimaging. The futureresearchactivitiesof theCNSgroupare focusedon: languageprocessingand implicit learning,readingacquisition&developmentaldyslexia,emotionalprocessing&dementiadisorders,andneurobiologicallyrealisticmodellingoflanguageprocessing.B-Productivity2014-presentTheCNSGrouphaspublished30peer-reviewedscientificarticlesand4bookchapters.Duringthisperiod, theworkof theCNSgrouphasbeen cited∼2100 times (∼4400 times since2011;WebofScience).The CNS group is funded by FCT projects (∼200 k€; 2014-2019), Post-doc grants (∼150 k€;2015-2019), and has secured a long-term Dutch Gravitation grant (Language in Interaction,2013-2023,∼3000k€/year)Supervision:3Post-Docs,4PhDstudents,7MScstudents.Conferencesandexternalcommunications:organized2conferencesandmorethan5eventsforSciencedisseminationtothegeneralpublic.C-CollaborationsThemembersoftheCNSgrouphaveongoingcollaborations,including:1. Regional Hospital of Faro (pharmacological intervention and cognitive function;dexmedetomidine/propofol).2.HospitalParticulardoAlgarve(dyslexia).3.Nationalinstitutions(since2014:10publications,1Post-Docgrant):

• DepartmentofPsychology,UniversidadedoLisboa(dyslexia);• Department of Psychology, Universidade do Porto (implicit sequence learning, music

perception,dyslexia).4. International institutions (long-standing,more than a decade; since 2014: 5 publications, 1Post-Docgrant,3PhDsgrant,1long-termgrant,2013-2023):

• Neurobiology of Language Department, Max Planck Institute for Psycholinguistics(neurobiologicallyrealisticmodellingoflanguageprocessing);

• NeurocognitionofLanguageResearchGroup,DondersInstituteforBrain,CognitionandBehaviour(cognitiveneuroscienceoflanguage);

• COST-ACTION-EuropeanLiteracyNetworkD-Publications2014-presentAraújo, S., Faísca, L., Reis, A.,Marques, J.F., & Petersson, K.M. (2016). Visual naming deficits indyslexia: An ERP investigation of different processing domains. Accepted for publication inNeuropsychologia.

Araújo,S.,Reis,A.,Faísca,L.,&Petersson,K.M.(2016).Brainsensitivitytowordsandthe“wordrecognition potential”. In D. Marques, & J. H. Toscano (Eds.), De las neurociencias a laneuropsicologia: el studio del cerebro humano. Barranquilla, Colombia: CorporaciónUniversitariaReformada.

Araújo, S., Faísca, L., Bramão, I., Reis, A., & Petersson, K. M. (2015). Lexical and sublexicalorthographic processing: An ERP study with skilled and dyslexic adult readers. Brain andLanguage,141,16-27.doi:10.1016/j.bandl.2014.11.007.

Araújo,S.,Reis,A.,Petersson,K.M.,&Faísca,L.(2015).Rapidautomatizednamingandreadingperformance: A meta-analysis. Journal of Educational Psychology, 107(3), 868-883.doi:10.1037/edu0000006.

Araújo, S., Faísca, L., Bramão, I., Petersson, K. M., & Reis, A. (2014). Lexical and phonologicalprocessesindyslexicreaders:Evidencesfromavisual lexicaldecisiontask.Dyslexia,20,38-53.doi:10.1002/dys.1461.

Basnakova,J.,Weber,K.,Petersson,K.M.,VanBerkum,J. J.A.,&Hagoort,P.(2014).Beyondthelanguage given: The neural correlates of inferring speaker meaning. Cerebral Cortex, 24(10),2572-2578.doi:10.1093/cercor/bht112.

Barriga-Paulino, C. I., Rojas-Benjumea, M. A., Rodríguez-Martínez, E. I., Gómez, C. M. (2015).Frontotemporo-occipital activity changes with age during a visual working memorydevelopmentalstudyinchildren,adolescentsandadults.NeuroscienceLetters,599,26-31.

Barriga-Paulino,C.I.,Rodríguez-Martínez,E.I.,Rojas-Benjumea,M.A.,Gómez,C.M.(2014).Slowwavematurationonavisualworkingmemorytask.BrainandCognition,88,43-54.

Bramão,I.,Reis,A.,Petersson,K.M.,&Faísca,L.(2016).Knowingthatstrawberriesareredandseeing red strawberries: The interaction between surface colour and colour knowledgeinformation. Journal of Cognitive Psychology. Advance online publication.doi:10.1080/20445911.2016.1182171.

CardosoS,SilvaD,MarocoJ,deMendonçaA,GuerreiroM.(2014).Non-literallanguagedeficitsinmildcognitiveimpairment.Psychogeriatrics2014;14(4):222-228.

Cruz,A.L.,Santos,M.E.,Reis,A.,&Faísca,L.(2014).ValidaçãoPortuguesadeumtestebreveparaorastreiodaafasia(BesidedeLenguaje).Sinapse,14(1),9–17.

Faísca, L., Afonseca, S.,Martins, A.T., Gonçalves, G., Gomes, A., & Brüne,M. (2016). PortugueseAdaptation of Faux Pas Test and ToM Picture Stories Task. Accepted for publication inPsychopathology.

Faísca,L.,Araújo,S.,&Reis,A.(2015).Preditoresdascompetênciasdeescritanosprimeirosanosdaescolaridade.InA.C.Naschold,A.R.Guaresi,&V.W.Pereira(Eds.),AprendizadodaLeituraedaescrita:aciênciaeminterface(pp197-236).EDUFRN:Natal.ISBN978-85-425-0506-1.

Folia,V.,&Petersson,K.M. (2014). Implicit structuredsequence learning:An fMRIstudyof thestructural mere-exposure effect. Frontiers in Psychology, 5: 41-53.doi:10.3389/fpsyg.2014.00041.

Gonçalves, G., Gomes, A., Ferrão,M.C., Parreira, T Santos, J., Giger, J-C., &Martins, A.T. (2015).Once Upon a Face: the Effect of Eye Size, Observer and Stimulus Gender on ImpressionFormation.CurrentPsychology,34,112-120.doi:10.1007/s12144-014-9244-3.

Lemos, I. & Faísca, L. (2015), Psycho-social adversity, delinquent pathway and internalizingpsychopathologyinjuvenilemaleoffenders.TheInternationalJournalofLawandPsychiatry,42-43:49-57.doi:10.1016/j.ijlp.2015.08.007.

Pacheco, A., Araújo, S., Faísca, L., de Castro, S. L., Petersson, K.M., & Reis, A. (2014). Dyslexia'sheterogeneity: Cognitive profiling of Portuguese children with dyslexia. Reading and Writing,27(9),1529-1545.doi:10.1007/s11145-014-9504-5.

PereiraA,deMendonçaA,SilvaD,GuerreiroM,FreemanJ,EllisJ.(2015).Enhancingprospectivememory inmildcognitive impairment:Theroleofenactment. JClinExpNeuropsychol.37 (8):863-877.

Reis, A., Bramão, I., Araújo, S., & Faísca, L. (2015). Análise temporal dos processos deagrupamentoealternânciaemprovasde fluênciaverbal.RevistaPortuguesadePsicologia,44,121-132.

Rodríguez-Martínez,E. I.,Barriga-PaulinoC. I.,Rojas-Benjumea,M.A.,Gómez,C.M. (2014).Co-Maturation of Theta and Low-beta RhythmsDuring ChildDevelopment. Brain Topography, 28(2),250-260.

Sales,C.,Wakker,P.Alves,P.&Faísca,L.(2015).MFCALCULATOR:AWeb-basedApplicationforAnalyzing Similarity. Journal of Statistical Software, 65, Code Snippet 2. doi:0.18637/jss.v065.c02.

Silva,S.,Faísca,L.,Araújo,S.,Casaca,L.,Carvalho,L.,Petersson,K.M.,&Reis.,A.(2016).Whentheeyes no longer lead: Familiarity and length effects eye-voice span. Accepted for publication inFrontiersinPsychology.

Silva,S.,Petersson,K.M.,&Castro,S.(2016).Rhythminthebrain:Ismusicspecial?InD.Marques,&J.H.Toscano(Eds.),DelasNeurocienciasalaNeuropsicologia:ElEstúdiodelCerebroHumano.Barranquilla,Colombia:CorporaciónUniversitariaReformada.

Silva,S.,Faísca,L.,Araújo,S.,Casaca,L.,Carvalho,L.,Petersson,K.M.,&Reis.,A.(2016).Toolittleortoomuch?Parafovealpreviewbenefitsandparafovealloadcostsindyslexicadults.AnnalsofDyslexia,66(2),187-201.DOI:10.1007/s11881-015-0113-z

Silva,S.,Folia,V.,Hagoort,P.,&Petersson,K.M.(2016).TheP600inImplicitArtificialGrammarLearning.CognitiveScience.Advanceonlinepublication.doi:10.1111/cogs.12343.

Silva,S.,Petersson,K.M.,&Castro,S.L.(2016).Theeffectsofordinalloadonincidentaltemporallearning. Quarterly Journal of Experimental Psychology. Advance online publication.doi:10.1080/17470218.2016.1146909.

Silva,S.,Faísca,L.,Araújo,S.,Casaca,L.,Carvalho,L.,Petersson,K.M.,&Reis,A.(2015).Toolittleortoomuch?Parafovealpreviewbenefitsandparafovealloadcostsindyslexicadults.AnnalsofDyslexia,66(2),187-201doi:10.1007/s11881-015-0113-z.

Silva,S.,Barbosa,F.,Marques-Teixeira,J.,Petersson,K.M.,&Castro,S.L.(2014).Youknowwhen:Eventrelatedpotentialsandtheta/beatpowerindicateboundarypredictioninmusic.JournalofIntegrativeNeuroscience,13(1),19-34.doi:10.1142/S0219635214500022.

Silva, S., Branco, P., Barbosa, F., Marques-Teixeira, J., Petersson, K.M., & Castro, S. L. (2014).Musicalphraseboundaries,wrap-upandtheclosurepositiveshift.BrainResearch,1585,99-107.doi:10.1016/j.brainres.2014.08.025.

Silva D, Guerreiro M, Faria C, Maroco J, Schmand BA, Mendonça Ad. (2014). Significance ofsubjectivememory complaints in the clinical setting. J Geriatr Psychiatry Neurol 2014; 27(4):259-265.

Van Leeuwen, T. M., Petersson, K.M., Langner, O., Rijpkema, M., & Hagoort, P. (2014). Colorspecificity in the human V4 complex: An fMRI repetition suppression study. In T. D.Papageorgiou,G.I.Cristopoulous,&S.M.Smirnakis(Eds.),AdvancedBrainNeuroimagingTopicsin Health and Disease - Methods and Applications (pp. 275-295). Rijeka, Croatia: Intech.doi:10.5772/58278.

VanLeeuwen, T.M., Lamers,M. J. A., Petersson,K.M., Gussenhoven, C., Poser, B.,&Hagoort, P.(2014).Phonologicalmarkersofinformationstructure:AnfMRIstudy.Neuropsychologia,58(1),64-74.doi:10.1016/j.neuropsychologia.2014.03.017.

VosSJ,VerheyF,FrölichL,KornhuberJ,WiltfangJ,MaierW,PetersO,RütherE,NobiliF,MorbelliS,FrisoniGB,DrzezgaA,DidicM,vanBerckelBN,SimmonsA,SoininenH,KoszewskaI,MecocciP,TsolakiM,VellasB,LovestoneS,MuscioC,HerukkaSK,SalmonE,BastinC,WallinA,NordlundA,deMendonçaA, SilvaD, Santana I, LemosR,EngelborghsS,VanderMussele S;Alzheimer’s

DiseaseNeuroimagingInitiative,Freund-LeviY,WallinÅK,HampelH,vanderFlierW,ScheltensP, Visser PJ. (2015). Prevalence and prognosis of Alzheimer's disease at the mild cognitiveimpairmentstage.Brain,138(Pt5):1327-1338.

Weber,K.,Christiansen,M.,Petersson,K.M.,Indefrey,P.,&Hagoort,P.(2016).fMRIsyntacticandlexical repetition effects reveal the initial stages of learning a new language. The Journal ofNeuroscience,36,6872-6880.doi:10.1523/JNEUROSCI.3180-15.2016.