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ANNUALREPORT2012SCHOOLOFPHARMACEUTICALSCIENCESGENEVA-LAUSANNE2ANNUALREPORT2012ANNUALREPORT20123CONTENTSCHAPTERSCONTENTS3DIRECTIONANDADMINISTRATION5RESEARCHUNITS7COMMITTEESOFTHESCHOOLOFPHARMACEUTICALSCIENCES8STAFF11BUDGET15BIOPHARMACEUTICALS19LIFESCIENCESMASSSPECTROMETRY23PHARMACEUTICALANALYTICALCHEMISTRY27PHARMACEUTICALBIOCHEMISTRY31PHARMACEUTICALTECHNOLOGY37PHARMACOCHEMISTRY41PHARMACOGNOSY45PHARMACOLOGY49PHYTOCHEMISTRYANDBIOACTIVENATURALPRODUCTS53CLINICALPHARMACEUTICAL57COMMUNITYPHARMACY59HOSPITALPHARMACY63DOCTORALPROGRAM65PROFESSORHONORARY694ANNUALREPORT2012ANNUALREPORT20125DIRECTIONANDADMINISTRATIONPRESIDENTProfPierre-AlainCARRUPTVICE-PRESIDENTSProfGerritBORCHARDandProfJean-LucWOLFENDERADMINISTRATORMrsAnnickdeMORSIERADMINISTRATIVEASSISTANTMrsDanielleCOOSEMANS-VESINSECRETARYMrsDominiqueHUNZIKERSTUDENTS'ADVISORDrElisabethRIVARAMINTENSTUDENTSSECRETARYMrsElisaMASSONMrsElenaONATEPROGRAMMDOCTORALSECRETARYMrsMyrthaCOPININFORMATICSTAFFM.
LorisFRANCOM.
YannMANET6ANNUALREPORT2012ABBREVIATIONSPOProfesseurordinairePASProfesseurassociéPAProfesseurassistantPTProfesseurtitulairePIProfesseurinvitéPDPrivatdocentMERMatred'enseignementetderechercheCSCollaborateurscientifiqueCCChargédecoursCEChargéd'enseignementANNUALREPORT20127RESEARCHUNITSBBIIOOPPHHAARRMMAACCEEUUTTIICCSSLLIIFFEESSCCIIEENNCCEESSMMAASSSSSSPPEECCTTRROOMMEETTRRYYProfGerritBORCHARD,POProfGérardHOPFGARTNER,PODrOlivierJORDAN,MERDrEmmanuelVARESIO,MERPPHHAARRMMAACCEEUUTTIICCAALLAANNAALLYYTTIICCAALLCCHHEEMMIISSTTRRYYPPHHAARRMMAACCEEUUTTIICCAALLBBIIOOCCHHEEMMIISSTTRRYYProfJean-LucVEUTHEY,POProfLeonardoSCAPOZZA,POProfSergeRUDAZ,PASDrYogeshvarKALIA,MERDrDavyGUILLARME,CEPPHHAARRMMAACCEEUUTTIICCAALLTTEECCHHNNOOLLOOGGIIEESSPPHHAARRMMAACCOOGGNNOOSSYYProfEricALLEMANN,POProfMurielCUENDET,PASDrFlorenceDELIE-SALMON,MERDrPhilippeCHRISTEN,MERDrNorbertLANGE,MERDrPascalFURRER,CEPPHHAARRMMAACCOOCCHHEEMMIISSTTRRYYPPHHAARRMMAACCOOLLOOGGYYProfPierre-AlainCARRUPT,POProfUrsRUEGG,PO,(until31.
7.
2012)CCOOMMMMUUNNIITTYYPPHHAARRMMAACCYYPPRROOTTEEOOMMIICCCCLLIINNIICCAALLProfOlivierBUGNON,PASProfDenisHOCHSTRASSER,POPPHHYYTTOOCCHHEEMMIISSTTRRYY&&BBIIOOAACCTTIIVVEECCLLIINNIICCAALLPPHHAARRMMAACCOOLLOOGGYYNNAATTUURRAALLPPRROODDUUCCTTSSProfJean-LucWOLFENDER,POProf.
ChantalCSAJKA,PASDrEmersonFERREIRAQUEIROZ,MERProfPierreDAYER,PODrElisabethRIVARA-MINTEN,CEProfJulesDESMEULES,PASHHOOSSPPIITTAALLPPHHAARRMMAACCYYEEXXTTEERRNNAALLPPRROOFFEESSSSOORRProfPascalBONNABRY,PASProfTudorARVINTE,PTProfAndréPANNATIER,PASDrMartinBERNHARDT,CEDrLaurentDECOSTERD,PDDrChristianKOLLER,CEMrsMichèleIMFELD,CEDrPhilippeLAURENT,CCDrAlainMERKLI,CCDrNicolasSCHAAD,PDDrFarshidSADEGHIPOUR,CEProfJean-LucSALOMON,PTProfYannSEIMBILLE,PADrChristianSIERRO,CEDrChristianSTAUB,CCDrCyrusTABATABAY,PD8ANNUALREPORT2012COMMITTEESOFTHESCHOOLOFPHARMACEUTICALSCIENCESCCOOMMMMIITTTTEEEEFFOORREEDDUUCCAATTIIOONNAANNDDTTEEAACCHHIINNGGPPRROOGGRRAAMMProfJean-LucWOLFENDER,PresidentProfEricALLEMANNMrsElenaONATEProfGerritBORCHARDProfAndréPANNATIERProfOlivierBUGNONDrElisabethRIVARAMINTENProfPierre-AlainCARRUPTProfSergeRUDAZProfChantalCSAJKAProfLeonardoSCAPOZZADrFlorenceDELIE-SALMONDrNicolasSCHAADProfJulesDESMEULESDrEmmanuelVARESIOCCOOMMMMIITTTTEEEERREEGGLLEEMMEENNTTAANNDDEEQQUUIIVVAALLEENNCCEEProfMurielCUENDET,PresidentProfPierre-AlainCARRUPTDrElisabethRIVARAMINTENDrFlorenceDELIE-SALMONProfSergeRUDAZMrsElenaONATEProfJean-LucWOLFENDERCCOOMMMMIITTTTEEEECCAADDEESSProfGerritBORCHARD,PresidentProf.
PascalBONNABRYDrEmersonFERREIRAQUEIROZMmeDanielleCOOSEMANSDrYogiKALIAProfMurielCUENDETSSEECCUURRIITTYYCCOOMMMMIITTTTEEEEProfLeonardoSCAPOZZA,PresidentMrsDanielleCOOSEMANSDrNorbertLANGEDrPhilippeCHRISTENMrOlivierPETERMANNMrsAnnickdeMORSIERDrElisabethRIVARA-MINTENM.
CédricSCHELLINGCCOONNTTIINNUUIINNGGEEDDUUCCAATTIIOONNPPRROOGGRRAAMMAANNDDPPUUBBLLIICCCCOOUURRSSEESSCCOOMMMMIITTTTEEEEProfGerritBORCHARD,PresidentProfPascalBONNABRYProfMurielCUENDETProfOlivierBUGNONMmeEmilieREGINATOPPRREEMMIISSEESSCCOOMMMMIITTTTEEEEProfGérardHOPFGARTNER,PresidentProfEricALLEMANNM.
LorisFRANCOProfGerritBORCHARDProfSergeRUDAZDrFlorenceDELIEProfLeonardoSCAPOZZAMrsAnnickdeMORSIERProfJean-LucWOLFENDERIITTCCOOMMMMIITTTTEEEEProfPierre-AlainCARRUPT,PresidentM.
LorisFRANCOProfSergeRUDAZDrNorbertLANGEDrEmmanuelVARESIOM.
YannMANETProf.
Jean-LucWOLFENDERANNUALREPORT20129DDOOCCTTOORRAALLPPRROOGGRRAAMMCCOOMMMMIITTTTEEEEProfLeonardoSCAPOZZAandProfGérardHOPFGARTNER,co-PresidentsProfGerritBORCHARDDrYogeshvarKALIAProfOlivierBUGNONProfAndréPANNATIERMrsMyrthaCOPINMmeDominiqueSTORZProfMurielCUENDETProfJean-LucWOLFENDERDrNorbertLANGESSEECCOONNDDAARRYYEEDDUUCCAATTIIOONNCCOOMMMMIITTTTEEEEMrsAnnickdeMORSIER,PresidentDrPhilippeCHRISTENDrElisabethRIVARA-MINTENM.
LorisFRANCODrEmmanuelVARESIODrPascalFURRER10ANNUALREPORT2012ANNUALREPORT201211STAFFPPRROOFFEESSSSOORRSSEricALLEMANNMurielCUENDETJean-LucSALOMONTudorARVINTEJulesDESMEULESLeonardoSCAPOZZAPascalBONNABRYDenisHOCHSTRASSERYannSEIMBILLEGerritBORCHARDGérardHOPFGARTNERCyrusA.
TABATABAYOlivierBUGNONAndréPANNATIERJean-LucVEUTHEYPierre-AlainCARRUPTSergeRUDAZ(since1.
11.
2012)Jean-LucWOLFENDERChantalCSAJKA(since1.
11.
2012)UrsRUEGG(until31.
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2012)MMEERRPhilippeCHRISTENEmersonFERREIRAQUEIROZNorbertLANGEChantalCSAJKA(until30.
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2012)OlivierJORDANSergeRUDAZ(until31.
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2012)FlorenceDELIE-SALMONYogeshvarKALIAEmmanuelVARESIORREEAADDEERRSSChinBinEAPAlainMERKLIChristianSTAUBPhilippeLAURENTLLEECCTTUURREERRSSMartinBERNHARDTDavyGUILLARMEElisabethRIVARA-MINTENJulienBOCCARDMichèleIMFELDFarshidSADEGHIPOURAntoineDAINAChristianKOLLERChristianSIERROPascalFURRERKarlPERRONPPRRIIVVAATTDDOOCCEENNTTJohnnyBENEYLaurentDECOSTERDRemoPEROZZONicolasSCHAADGeorgesZELGERRREESSEEAARRCCHHAASSSSOOCCIIAATTEESSIngoALBERTIMoniaGUIDIMichaelMOELLERWilliamBISSONOlivierJORDANAlicePANCHAUDCinziaDEUTSCHSTELLABeatriceKAUFMANNRemoPEROZZOLaurentGEISERSophieMARTELMarie-PauleSCHNEIDERJulietaGRADINARUSSEENNIIOORRRREESSEEAARRCCHHEERRSSClaudiaAVELLOSIMOESPIRESAlessandraNURISSOJulieSCHAPPLERAntoineDAINA(until28.
02.
2012)LucilePERNOTSCHILTZMagaliZEISSEROlivierDORCHIESThomasRIIS-JOHANNESSEN12ANNUALREPORT2012PPHHDD.
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SSTTUUDDEENNTTSSMokhtarYoussefACHACHEOliviaFRANCOISAleksandraPELCZARSKABandarAbdullahALGHANEMKatrinFUCHSAuréliePERIATChiaraAMBUEHLAurélieGERTSCHBénédictePETITMarcoANASTASIVérénaGOTTACharlottePETITVirginieANCRENAZAlexandreGRAND-GUILLAUMESurekhaPIMPLEIsabelleANGUISHPatriciaGRAVENCatherinePLUESS-SUARDMonaARAB-ALAMEDDINEAnthonyGROGNUZJohannaPCHEIMVilmaARMOSKAITELilianeGSCHWINDTiffanyPORTALeireAZURMENDIRomainHAUDECOEURJuliePRADALLutzASMUSGesineHEUCKSakthikumarRAGUPATHYFlaviaBADOUDRuhollahHEYRANIChristianREICHERTLoséniBENGALYMélanieHOERLEMartaRODRIGUEZEmmanuelBENSIMONPernillaHOFFMANNStéphanieROMANDDanielBIASSEValiaHUMBERT-DELALOYELucieRYCKEWAERTNadineBOHNIKuntheavyINGTatjanaSAJICMichelaBOIAmeenaJESAIMANIOmarShoukrySAKRGrégoireBONVINSemaKADERLINawalSEKKATMarijaBOSILKOVSKALaure-ZoéKAESTLIJohnathanSIDIBERalitzaBOUBEVADhavalKALARIAAnne-LaureSIDLER-MOIXLucieBOUCHOUDIsabelleKOHLERLiudasSLEPIKASLaraBRAMBILLAHakimKRATOUDanySPAGGIARITobiasBRUDERERMariaLAPTEVAAlineSTAUBSPORRIAlbanBUJARDLeonardoLAUCIELLONathalieSTRANSKY-HEILKRONDelphineCARLICélineLEBOURDONNECAurélienTHOMASSouraCHALLALAntoineLESURNataliaTIBERTIAdelineCHAUVINVirginieLICKERDavidTONOLIYongCHENNicoleLONGONIStéphanieTROXLEREvaCHOONGMarcoMAGISTRIGalleVACHEROlivierCICLETJulienMARQUISAnastasiaVENTOURIDidiaCOELHOGRACANiloufarMARSOUSINathalieVERNAZAndreaCRISTIANICarolineMATHONFranoisVERSACESandrineCUDREHishamMOHAMEDMariekeVEURINKElyesDAHMANEMohamedMOHAMEDVéroniqueVIETTESarradeVALENCEDELAMINARDIEREAlessandraMONACOKarineVUIGNIERJulienDEGLONIvanaNOVAKOVICMichelWAGNERJean-ChristopheDEVAUDSusannNUSSBAUMERYvonneWESTERMAIERClaudiaDITOMMASONilsOBERHAUSERCélineXAYAPHOUMMINESachinDUBEYVéraOLDRATIMinetteZEUKENGPhilippeEUGSTERHuiSongPAKYingZHANGElisabethFAVREDavidPALMEROAnneZUFFEREYQuentinFAVRE-GODALChiaraPASTORIMaria-FernandaZULUAGACéciliaFORTUGNOEmiliePATOISVincentZWICKANNUALREPORT201213PPOOSSTT--DDOOCCTTOORRAALLSSTTUUDDEENNTTSSLutzASMUSSzabolcsFEKETEFlorenceMILLERAndrejBABICAnne-LaureGASSNERAndreasNIEVERGELT-MEIERFlaviaBADOUDTaisGRATIERIAlessandraNURISSOCindyBENODAminaHAOUALAHajerOUERTATANISamuelBERTRANDAna-KarinJACOBSONJuliePATTEREUTENAUERLiseBREANTSébastienKICKADhananjayaSAHOOGianpaoloCHIRIANOAbhinandanKOTIKANYADANAMCesarSERNAJIMENEZBenjaminDEBRUSMiriamKOVACSKiranSONAJESergioDELRIOSANCHOAgataKRANCJPIETRUCCIMagdalenaSWIDERSKACristinaDIEZAmandineLEFOLLOTECSebastienTARDYSachinDUBEYGuillaumeMARTIAlessandraZIZZARIKarineDUMONTETMONDONFlorenceMEHLMariaZULUAGAESTRADACCOO--DDIIRREECCTTIIOONN((CCOO--TTUUTTEELLLLEE))CristinaCASETTAAnnasaraHANSSONHanitraRAVELOJAONACeciliaFORTUGNOSamiaOUERTANIAADDMMIINNIISSTTRRAATTIIVVEESSTTAAFFFFValérieCAZORLADominiqueHUNZIKERAudreyPARVEXDanielleCOOSEMANSNathalieLAEDERACHSylviaPASSAQUAY-RIONMyrthaCOPINYannMANETGiuliaPELLEGRINOAnnickdeMORSIERElisaMASSONNatalieSCHREGLENicoleDECREYMadeleineMEISTERDominiqueSTORZLorisFRANCOElenaONATEFlorenceVONOWTTEECCHHNNIICCAALLSSTTAAFFFFSaidBENOHOUDSylvieGUINCHARDOphéliePATTHEY-VUADENSNathalieBOULENSTayebJBILOUMarcoPERDIGAOMartineCABOBéatriceKAUFMANNOlivierPETERMANNBrigitteDELAVYElianeKUEHNEmilieREGINATOCaroleDUPRAZLaurenceMARCOURTColetteSAUTYChristopheFRANCEYKarineNDJOKOIOSETCédricSCHELLINGFabriceGILLERATIrenaNIKOLOVASTANKOVACatherineSIEGFRIED-MICHELChantalGRIVETJessicaORTELLIEmmanuelleSUBLETSSTTAAGGIIAAIIRREESSLidaALEXIOUMarcosFERREIRAQUEIROZThomasRIIS-JOHANNESSENChiaraAMBUEHLStéphaneGAMEIROMarie-AstridRODASAntonioAZZOLLINIAmparoGARCIALOPEZPatrickRODRIGUEZSandraCristinaCAMPOSDEJESUSEmanuelaGIACOMELLILionelSACCONNAYElisaCARENZAFlorianeGROELLSylvainSCHNEECélineCONANThibaultJARRIGEAlexandraSEVINJean-PierreDEJOFFREYYildizKUPPERMaddalenaSGUIZZATOJoséDESOUSALIMANETOSilviaLOVERAMayankSINGHALHortenseDECROOCQMargauxMIGNOTMargheritaTAMBALOMariagraziaDIMARCOMarionPETERSHenriTHOOSSouniaDJEMILBénédictePETIT-JEANSimoneVIGNOLACarolinaDOSSANTOSPASSOSMarinePEUCHMAURKyokoWATANABEClaraESTEVECOLSClaudiaQUINTINODAROCHAMariaLuizaZERAIK14ANNUALREPORT2012ANNUALREPORT201215BUDGETBUDGET2012*STAFFSALARY111'858'909.
--((TTAABBLLEEAAUU11))FONCTIONNEMENTBUDGETSECTION1'249'497.
--((TTAABBLLEEAAUU22))TTOOTTAALLBBUUDDGGEETTSSAALLAARRYYAANNDDFFUUNNCCTTIIOONNMMEENNTT1133''110088''440066.
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----((TTAABBLLEEAAUU33))SWISSNATIONALSCIENCESFOUNDATION1'860'108.
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----((TTAABBLLEEAAUU22))TTOOTTAALLBBUUDDGGEETTEEPPGGLL1188''556666''880011.
.
----22*STAFF2012NUMBEROFPEOPLE3:3181Withoutsocialsecuritycontributions2including:-contributionEtatVDCHF5'093'014.
—-subsidiesuniversitaireintercantonale"AIUCHF1'450'000.
—3TotalnumberofpeopleworkingatEPGLduring201216ANNUALREPORT2012TABLEAU1TOTALBUDGETSTAFF(9.
87MIO)TABLEAU2TOTALPUBLICANDEXTERNALFUNDSassistantsPATProfessorsLecturers3.
06Mio2.
72Mio2.
38Mio1.
62Mio020000004000000600000080000001000000012000000140000002006200720082009201020112012FNRSAUTRESDIPANNUALREPORT201217TABLEAU3OPERATIONALBUDGET(1.
24MIO)ANDINVESTISSEMENT(0.
59MIO)librarychf60'000Educationchf75'000Doctoralschoolchf30'000Archampschf55'000OperatingbudgetforTPsectionchf100'000Investissementchf591'594Operatingbudgetoflaboratorieschf852'700OperatingbudgetofSectionchf100'000Veuthey;109'921Hopfgartner;90'373Carrupt;86'078Scapozza;128'531Borchard;79'188Wolfender;100'453Ruegg;34'904Allémann;108'216Cuendet;80'737pharmaciepratique;88'584Allemann;55'831Carrupt;48'554Veuthey;56'886Wolfender;53'422Cuendet;49'834Scapozza;62'782Hopfgartner;50'258Borchard;45'860Pharmaciepratique;40'000section;42'633TP;85'534ALLOCATIONINVESTMENTBUDGET(CHF591'594)ALLOCATIONOPERATIONALBUDGET(CHF852'700)18ANNUALREPORT20122012ATAGLANCEStaff(headcount)318Students:353-Bachelor241-Master108-Masterofadvancedstudies4Ph.
D.
students126TotalbudgetCHF18.
5MioPatentsPublicationswithimpactfactorPublicationswithoutimpactfactorPresentations&postersBooksandchaptersNumberofprojectsatFNRSandassimilatedProjectsofcollaborationwiththeindustryPh.
D.
Thesispresentedin201251454019228444714ANNUALREPORT201219BIOPHARMACEUTICALSPPRROOFFEESSSSOORRGerritBORCHARDMMEERROlivierJORDANRREESSEEAARRCCHHAASSSSOOCCIIAATTEESSAANNDDLLEECCTTUURREERRSSMichaelMLLERPPOOSSTTDDOOCCTTOORRAALLSSTTUUDDEENNTTSSRalitzaBOUBEVAPPHH.
.
DD.
.
SSTTUUDDEENNTTSSKatrinFUCHSJohannaPOECHEIMOmarSAKR(extramuros)FlorianeGROELLSakthikumarRAGUPATYGalleVACHERMohamedMOHAMEDChristianREICHERTCCOO--SSUUPPEERRVVIISSIIOONN((CCOO--TTUUTTEELLLLEE))SandraCristinaCAMPOSDEJESUSUniversityofCoimbra,PortugalElisaCARENZAInstitutdeCiènciadeMaterialsdeBarcelona,SpainAnnasaraHANSSONUniversityofLyon,FranceAADDMMIINNIISSTTRRAATTIIVVEEAANNDDTTEECCHHNNIICCAALLSSTTAAFFFFValérieCAZORLACatherineSIEGFRIEDEmmanuelleSUBLETTayebJBILOUSSPPEECCIIFFIICCRREESSEEAARRCCHHFFIIEELLDDSSBiopharmaceuticsdescribestheinteractionofbiologicalsystemsinvolvedinabsorption,distribution,metabolism,elimination,butalsotoxicityandimmunerecognitionofdrugsandtheirformulationsandcarriersystems.
Theadaptationofdruganddrugcarrierpropertiesthenisdefinedbyobservationofthesebiologicalsystems.
Withanexpertiseincell-basedassaydevelopment,formulationofmacromolecules,thedesignofpolymericdrugcarriersystems("nanomedicines")andfunctionalizedbiopolymers,thegroupofBiopharmaceuticsfocusesonthefieldsofoncologyandimmunotherapy.
InthepastyearwehaveforinstanceestablishedthatcertainligandsoftheToll-likereceptor2(TLR2),areceptorinvolvedinpathogenrecognitionandexpressedinepithelialaswellasimmunecells,isactuallyinvolvedintheregulationoftightjunctionpermeabilityinbronchialepithelia.
Auniquemechanism,involvingaspecificproteinkinase,wasidentifiedtoberesponsibleforthedecreaseinepithelialpermeabilityonligationofTLR2.
Thisobservationmayindeedbeusedinthedevelopmentofnewstrategiesforinflammatoryrespiratorydiseases.
Anotherproject,stillinthedomainofimmunerecognition,focusesonthecombinationofseveralligandsofdifferentpathogenpatternrecognitionreceptors(PRRs).
Thesearelocatedintheendosomalcompartment(TLR)andinthecytosol(NOD2),andtheirsimultaneousligation,alongwithantigenpresentation,issupposedtoyieldenhancedimmuneresponses.
Invitro,thisstrategyhasalreadyresultedinmassivereleaseofpro-inflammatorycytokinesfrombothepithelialcellandmacrophages.
2013willseetheproof-of-conceptofthisstrategytoimprovemucosalvaccinationagainstM.
tuberculosis.
Thepreparationandapplicationofbiopolymersisoneofthemainfociofthegroup.
Thesepolymers,asatechnologyplatform,areappliedtotheformulationofmacromoleculardrugsaswellasdrugsoflowsolubility,andtointeractwithcellsofdifferentoriginwiththepurposetochangetheirphenotypewithregardtoatherapeuticaloutcome.
In2012,theinvitrophaseofaprojectfocusingonthesynthesisandtestingofchitosanderivativestoimproveskincelladhesion,differentiationandproliferationinwoundhealingwassuccessfullyconcluded.
Thechitosanderivativewasfurthercombinedwitha20ANNUALREPORT2012compoundoftheextracellularmatrix,chondroitinsulfate,toformself-assemblingnanocarrierssystemstobeappliedtoslow-healingwounds.
Thisprojectwillbecontinuedthisyearandwillyieldfirstinvivoresults.
Inthefieldofoncology,weinvestigatemicrospheresreleasingananti-angiogenictyrosinekinaseinhibitor,sunitinib,totreathepatocarcinoma.
Thebioactivityofthereleasedinhibitorwasconfirmedincellculturemodelsandinvivoonrabbittumormodel.
Resultswerefavourablyreceivedinclinicalcongresses.
Inanotherproject,nanocomposite-basedinjectablecarriersforthetreatmentofspinemetastaseshavebeendesignedtocombinethermaltherapyandchemotherapy.
Invitrostudiesonprostatecancercellsdemonstratedthebioactivityoftheelutedantiblasticagent.
Insitugellingsystemscapableofbonereinforcementhavebeenobtained,inviewofosteolyticvertebrastabilization.
Combinedwithitsheat-generationability,thecarrierholdspromisesforbonemetastaseslocaltreatment.
Thisproject,carriedoutincooperationwithEPFL(Prof.
H.
Hofmann)andInselHospital,Bern(Prof.
G.
Thalmann),isfundedbytheSwissNationalScienceFoundation.
Intermsofproteinformulation,wehaveshowntheconceptof"non-covalentPEGylation"tobeavalidapproachforcertainexcipientsdevelopedbyus.
Anongoingproject,performedwiththehelpoftheDept.
ofPharmaceuticalBiotechnologyattheHochschuleBiberach(Germany;Prof.
HannemannandDr.
R.
Handrick),isnowaimingatincreasingthestrengthofinteractionbetweenthePEG-excipientandtheprotein.
Inordertobeableworkwithatherapeuticallyrelevantprotein,weestablishedfacilitiesanddevelopedanadvancedmethodfortheexpressionandpurificationofgranulocyte-colonystimulatingfactor(G-CSF).
Anewproject,startedinSeptember2012,nowfocusesonthecharacterizationoftheinteractionofproteindrugaggregateswiththeimmunesystemaftersubcutaneousinjection.
Againintendingtoworkwitharelevantprotein,weestablishedup-anddownstreamprotocolsforinterferon-alpha,acytokineusedinthetherapyofhepatitisandrecurrentmelanoma.
Inthefuture,wewillseektoincreaseourknowledgeintheformulationofcarriersystemsandtheirinteractionwithbiologicalsystemstoobtainrationalconceptsforthedesignofnanomedicines.
OOUUTTSSTTAANNDDIINNGGPPUUBBLLIICCAATTIIOONNSSA.
Hansson,O.
Jordan,P.
Rousselle,F.
FalsonandG.
Borchard,TheuseofsmallsyntheticRGDpeptidesinwoundhealing:Promotionofcelladhesionandmigrationinkeratinocytesandfibroblasts.
InternationalJournalofPharmaceutics439,73-80.
G.
Borchard,B.
FlühmannandS.
Mühlebach.
Nanoparticleironmedicinalproducts–Requirementsforapprovalofintendedcopiesofnon-biologicalcomplexdrugs(NBCD)andtheimportanceofclinicalcomparativestudies.
RegulatoryPharmacologyandToxicology64,324-328.
PPAARRTTIICCUULLAARRPPRROOJJEECCTTSSIINNIITTIIAATTEEDDAprojectfocusingontheuseofsuperparamagneticironoxideparticles(SPION)fordiagnosisandtherapyofcerebralischemiawasinitiatedwiththeInstituteofMaterialSciences(ICMAB)andtheNeurovascularResearchLaboratoryatValld'HebronHospital(bothinBarcelona,Spain).
CCOONNGGRREESSSSEESSProf.
G.
Borchardwasco-organizerofthe5thSwissPharmaScienceDayinBern,Switzerland,inAugust2012,andtheRencontrePharmapeptidesinArchamps(France)inNovember2012.
11.
.
PPUUBBLLIICCAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE66))1.
1SCIENTIFICPUBLICATIONS(WITHIMPACTFACTOR)101.
2SSCCIIEENNTTIIFFIICCPPUUBBLLIICCAATTIIOONNSS((WWIITTHHOOUUTTIIMMPPAACCTTFFAACCTTOORR))322.
.
PPOOSSTTEERRSSPPRREESSEENNTTAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE77))2.
1POSTERSPRESENTATIONS1533.
.
OORRAALLPPRREESSEENNTTAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE99))3.
1CONGRESSES&SYMPOSIA15ANNUALREPORT20122144.
.
TTHHEESSIISSPPRREESSEENNTTEEDD44.
.
11.
.
IINNTTRRAA--MMUURROOSSTTHHEESSIISSHanssonAnnasaraPolymericcontrolledreleasesystemsforRGDpeptidesdeliveryinskinrepair.
UniversityofGeneva-2012Supervisor:Prof.
G.
BorchardCo-Supervisor:Dr.
O.
JordanVacherGaelleOralthinfilms(OTF)forvirosomalvaccines.
UniversityofGeneva-2012-thesisn°4515Supervisor:Prof.
G.
BorchardCo-Supervisor:Prof.
R.
Gurny55.
.
PPUUBBLLIICCRREESSEEAARRCCHHFFUUNNDDSS((FFNNSSRR,,NNIIHH,,CCTTII))SSWWIISSSSNNAATTIIOONNAALLSSCCIIEENNCCEEFFOOUUNNDDAATTIIOONNLocoregionaltreatmentofprostatecancermetastasestoboneusingimplant-mediatedhyperthermia,SNFNo.
31003A-127513/1Mainapplicant:O.
JordanCo-applicants:G.
Borchard,G.
Thalmann,H.
Hofmann,E.
DoelkerAllocation2012:CHF86'400Duration:3yearsStartingdate:201066.
.
PPAATTEENNTTSSS.
Kaderli,O.
Jordan,R.
GurnyUSprovisionalpatentapplicationUS61693803:Hybirdhydrogels,2012.
22ANNUALREPORT2012ANNUALREPORT201223LIFESCIENCESMASSSPECTROMETRYPPRROOFFEESSSSOORRGérarrdHOPFGARTNERMMEERREmmanuelVARESIOBBOOUURRSSIIRREEDD''EEXXCCEELLLLEENNCCEEKyokoWATANABEPPOOSSTTDDOOCCTTOORRAALLSSTTUUDDEENNTTSSAbhiKOTIKANYADANAMRAGHAVANPPHH.
.
DDSSTTUUDDEENNTTSSYoussefACHACHETobiasBRUDERERTatjanaSAJICBandarALGHANEMSandrineCUDREJonathanSIDIBEAiwettBILBAOPENAAntoineLESURDavidTONOLIDarioBOTTINELLITiffanyPORTAYingZHANGAADDMMIINNIISSTTRRAATTIIVVEEAANNDDTTEECCHHNNIICCAALLSSTTAAFFFFChantalGRIVETElianeKUEHNDominiqueSTORZGGEENNEERRAALLDDEESSCCRRIIPPTTIIOONNOOFFTTHHEEUUNNIITTTheLifeSciencesMassSpectrometry(LSMS)groupfocusesonthedevelopmentofmassspectrometry(MS)incombinationwithseparationtechniques(chip-basednanoUHPLC,nanoUHPLC,UHPLC)forthequantitativeandqualitativeanalysisoflowmolecularweightcompoundsandlargemoleculesinbiologicalmatrices.
ItiswellequippedwithvariousionisationtechniquesincludingMALDI,ESI,APCI,APPI,DESIandvarioustypesofmassspectrometerssuchasionmobility,quadrupole-time-of-flight,triplequadrupolelineariontrapsandFouriertransformioncyclotronresonancemassspectrometry.
IncollaborationwithexternalindustrialpartnersthegroupdevelopsnewMSstrategiesbasedonhigh-resolutionmassspectrometry,ultra-fastMS/(MS)acquisitionworkflows,MALDI-imaging,anddifferentialionmobilityspectrometryforlifesciences.
ThegroupisalsodevelopingsoftwareapproachesforanalyzinglargesetofMS/MSdatatosupportstructureelucidationindrugmetabolismandmetobolomics.
Variousstudiesareon-goinginthefieldoftoxicologytounderstandthebindingofreactivemetabolitestoproteins,toimagethedistributionofdrugsandtheirmetabolitesintissues,andtocharacterizetheeffectsofpharmaceuticalsonthemetabolome,lipidomeandproteomeofmammalsorcellsystems.
SSPPEECCIIFFIICCRREESSEEAARRCCHHFFIIEELLDDSSMetabolomic,LipidomicandProteomicAnalysesDevelopmentofQUAL/QUANMS/(MS)analyticalstrategiesforpharmaceuticalsandbiopharmaceuticalsincomplexmatricesHigh-ResolutionMassSpectrometryMassSpectrometryImagingDriedBloodSpotsAnalysisandrelatedtechniquesStructureelucidationbyLC-MSnandHighResolutionMSMiniaturizedseparationandinfusiontechniquesUltrafastandHigh-throughputAnalysisQualitycontrolandvalidationofanalyticalmethods24ANNUALREPORT2012SSPPEECCIIFFIICCPPRROOJJEECCTTSSIINNIITTIIAATTEEDDAANNDDRREECCOOGGNNIITTIIOONNSSProf.
Hottiger,UniversityofZurich,SRM-Proteomics11.
.
PPUUBBLLIICCAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE1111))1.
1SCIENTIFICPUBLICATIONS(WITHIMPACTFACTOR)91.
2BOOKCHAPTERS222.
.
PPOOSSTTEERRSSPPRREESSEENNTTAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE1122))2.
1POSTERSPRESENTATIONS633.
.
OORRAALLPPRREESSEENNTTAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE1133))3.
1CCOONNGGRREESSSSEESS&&SSYYMMPPOOSSIIAA1144.
.
TTHHEESSIISSPPRREESSEENNTTEEDD44.
.
11.
.
IINNTTRRAA--MMUURROOSSTTHHEESSIISSAntoineLESURNovelAnalyticalStrategiesfortheQuantitativeAnalysisofProteinsbyMassSpectrometryUniversityofGeneva,28September2012DavidTONOLIQualitativeandQuantitativeDeterminatinofDrugs,MetabolitesandtheirAdductstoProteinsinBiologicalMatricesbyLiquidChromatographyHyphenatedtoLowandHighResolutionMassSpectrometryUniversityofGeneva,29October201255.
.
RREESSEEAARRCCHHFFUUNNDDSS((IINNDDUUSSTTRRYYAANNDDAASSSSIIMMIILLAATTEEDD))CodeServiceDevelopmentResearchAmountend2012(CHF)Div.
SpectroService217'929FB_AlghanemRecherche18'235FondsNationalCRSII3_136282Recherche282'440518'60466.
.
DDEEVVIICCEESSIINNLLEENNDDMSdetectors1xESI-SingleQuadrupole2xESI-TripleQuadrupoleLinearIonTraps(QqQLIT)+peripherals1xMALDI-TripleQuadrupoleLinearIonTrap(QqQLIT)+peripherals2xQuadrupole-TimeofFlight(QqTOF)+peripherals1xQuadrupole-TimeofFlight(TripleTOF)+peripherals1xShimadzuLCMS80401xShimadzuMS8080Robot1xAutomatedchip-basednanospraysystem1xAutomateddriedbloodspots(DBS)system1xAutomatedSPEdevice1xMicrofractioncollectorLC1xDualUHPLCsystemwithcolumn-switchingvalves1xMicro-UHPLCpump1xMicro-LCsystemwithcolumn-switchingvalves1xNarrowboreLCsystemwithcolumn-switchingvalve1xDualnano-UHPLCsystemANNUALREPORT2012251xChip-basednano-LCsystem1xSplitlessnano-LCpump1xNano-LCsystemwithcolumn-switchingunit1x2Dnano-LCsystemwithcolumn-switchingunit1xShimadzuUHPLCNexeraCE1xCapillaryElectrophoresissystem26ANNUALREPORT2012ANNUALREPORT201227PHARMACEUTICALANALYTICALCHEMISTRYPPRROOFFEESSSSOORRSSSergeRUDAZJean-LucVEUTHEY(vice-chancellorsinceJanuary2011)SSEENNIIOORRRREESSEEAARRCCHHEERRSSDavyGUILLARMEJulieSCHAPPLERLaurentGEISERFabienneJEANNERETPPOOSSTTDDOOCCTTOORRAALLSSTTUUDDEENNTTSSSzabolcsFEKETEBenjaminDEBRUSAnne-LaureGASSNERFlorenceMEHLPPHH.
.
DDSSTTUUDDEENNTTSSMarcoANASTASIIsabelleKOHLERStéphanieROMANDLeireAZURMENDINiloufarMARSOUSIDanySPAGGIARIGrégoireBONVINAuréliePERIATKarineVUIGNIERAlexandreGRAND-GUILLAUMEPERRENOUDMartaRODRIGUEZCCOO--SSUUPPEERRVVIISSIIOONN((CCOO--TTUUTTEELLLLEE))::CristinaCASETTA(Turin,Italy)SamiaOUERTANI(Nantes,France)AADDMMIINNIISSTTRRAATTIIVVEEAANNDDTTEECCHHNNIICCAALLPPEERRSSOONNAALLNicoleDECREYCharlèneMEYLAN(apprentie)EmilieREGINATOChristopheFRANCEYJessicaORTELLICédricSCHELLINGGGEENNEERRAALLDDEESSCCRRIIPPTTIIOONNOOFFTTHHEEUUNNIITTThegroupfocusesitsactivitiesonseparationtechniquesmainlyliquidchromatography(LC),capillaryelectrophoresis(CE)andsupercriticalfluidchromatography(SFC)coupledwithvariousdetectors,includingmassspectrometry(MS)fortheanalysisofpharmaceuticalandbiopharmaceuticalcompounds.
Newchromatographicsupportsareevaluatedandoriginalstrategiestogainselectivityand/orsensitivityoftheanalyticalprocessaredeveloped.
Reductionoftheanalysistimeisalsostudied.
Specialfocusisgiventoenvironmentallyfriendlyanalyticalandsamplepreparationtechniques(greenchemistry).
Theresearchofthisgroupalsofocusesonthedevelopmentandtheuseofmethodsformathematicalandstatisticalanalysisofdataproducedfromchemicalinstrumentation.
Theuseofchemometrictoolsfordevelopinganalyticalmethods,determiningoptimisedorrobustconditions,aswellasfortreatingdatawithpatternrecognitiontechniquesareappliedinmanyprojectswithintheSchoolofPharmaceuticalSciencesandnumerousexternalacademicand/orindustrialcollaborations.
Threemainfieldsarecurrentlydeveloped,namelyDesignofexperiments(DOE),methodvalidation,anddatamining(exploratorydataanalysis).
Forthelatter,numerousimportantcollaborationsareunderprogress,particularlyinthefieldofmetabolism,metabolomics,andtoxicology.
Researchareasconsistin:pharmaceuticalanddrugsofabuseanalysisdopingsubstancesanalysischiralseparationofpharmaceuticalproductsstudyoftheimpactofsamplepreparationproceduresintheanalyticalprocesscharacterizationofchromatographicsupportsforpharmaceuticalsanalysisdrugmetabolismaffinitychromatography28ANNUALREPORT2012UHPLCandSFCseparationtechniquesscreeningmethodformetabolomicpurposedataminingSSPPEECCIIFFIICCRREESSEEAARRCCHHFFIIEELLDDSSLiquidchromatography(LC)Capillaryelectrophoresis(CE)Supercriticalfluidchromatography(SFC)Hyphenationtomassspectrometry(MS)SamplepreparationValidationChemometricsMetabolomicsToxicologyCCOOLLLLAABBOORRAATTIIOONNSSIINNIITTIIAATTEEDDWWIITTHHIINNDDUUSSTTRRYYCollaborationwithSanofi(France)11.
.
PPUUBBLLIICCAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE1155))1.
1SCIENTIFICPUBLICATIONS(WITHIMPACTFACTOR)221.
2SCIENTIFICPUBLICATIONS(WITHOUTIMPACTFACTOR)51.
3BOOKSORBOOKSCHAPTERS522.
.
PPOOSSTTEERRSSPPRREESSEENNTTAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE1177))2.
1POSTERSPRESENTATIONS2733.
.
OORRAALLPPRREESSEENNTTAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE1199))3.
1CONGRESSES&SYMPOSIA353.
2CONTINUINGEDUCATION&OPENTOTHEPUBLICLECTURES2244.
.
TTHHEESSIISSPPRREESSEENNTTEEDD44.
.
11IINNTTRRAA--MMUURROOSSTTHHEESSIISSK.
VUIGNIERAnalyticalstrategytocharacterizedrug-proteininteractions:fromhighthroughputtoin-depthanalysisCo-directeurdethèse:Pr.
P.
-A.
CarruptUniversitédeGenève–ThèseN°4489-201255.
.
PPUUBBLLIICCRREESSEEAARRCCHHFFUUNNDDSS((FFNNSSRR,,NNIIHH,,CCTTII))MMIISSCCEELLLLAANNEEOOUUSSSwissCenterforAppliedHumanToxicology(SCAHT).
S.
RUDAZ,M.
SAUGY.
Asteroidomicsapproachforinvestigationofmodulationofsteroidmetabolismandprofiles.
InCoreproject1:DiscoveryofToxico-BiomarkerPanelsusinga"SystemApproach".
Totalallocationchf600'000Duration4yearsStartingdate:2009Allocation2012:chf150'0002011-2013SwissNationalScienceFoundation:J.
-L.
Wolfender,t.
Farmer,s.
Rudaz.
"TargetedandmetabolomicstudyoftheearlychemicaleventsofthewoundresponseinA.
thaliana:dynamicsofsignallingandsearchforlongdistancebiomarkers.
"N°205320/135190–1:130'620CHFANNUALREPORT201229Commissionadministrativedel'UniversitédeGenève(COMAD),.
FinancialsupportforUPC2-WatersApplicant:D.
GuillarmeTotalAllocation:50'000.
—Allocation201:50'000CHFMarieCurieActionsIntraEuropeanFellowships(IEF),ConFirMS.
S.
RUDAZ(PI).
"ContaminantanalysisinFoodbyLiquidChromatographyMassSpectrometrytowardsagenericextractionandscreeningforpesticidesandveterinarydrugs"ProjectN°299455/Call(part)identifierFP7-PEOPLE-2011-IEFApplicant:S.
RudazAllocation2012:chf165'027.
41Startingdate:2012Totalallocation:euro184'709.
40CTIfundingapplication"Neurospectrum":"invitroassayforneurotoxicityassessment".
Co-applicants:L.
Stoppini(PI),K.
K.
Krause(CI),S.
Rudaz(CI).
CollaborationwithNeurix(Minibrain)N°13759.
1/RiskyinnovationsAllocation2012:chf77'674.
00Duration:2yearsStartingdate:2012Totalallocationchf579'00066.
.
RREESSEEAARRCCHHFFUUNNDDSS((IINNDDUUSSTTRRYYAANNDDAASSSSIIMMIILLAATTEEDD))CodeServiceDevelopmentResearchAmountfor2012(CHF)TeoxaneSA.
Genève,SuisseService–analyticalinvestigationsanddosages50'848.
00IndustrialfundsConfidential–CollaborationwithProf.
Wolfender200'000.
00Sanofi,FranceService–analyticalinvestigationsanddosages69'401.
0066.
.
11IINNSSTTRRUUMMEENNTTSSOONNLLOOAANNCode(LENDER)TotalAmount2012(CHF)UPCWaters(WATERS)170'260.
00CEAgilent(LAD)75'000.
00CEAgilent(LCT)75'000.
00UPLC-DADWaters(AGEMEL)120'000.
00G7100CEAgilentwithCE-MSinterfaceKitandG1310A1200isocraticpump(AGILENT)100'000.
00UPLCH-Class(Waters)(WATERS)160'000.
00HPLCSeries1500Waters(AGEMEL)65'000.
0077.
.
AAWWAARRDDSS&&DDIISSTTIINNCCTTIIOONNSSA.
-L.
GASSNER,S.
RUDAZ,J.
SCHAPPLERContributionofcapillaryzoneelectrophoresistotheanalysisofmonoclonalantibodydrugsAwardforexcellenceinoralpresentation,2ndpricetoA.
-L.
GassnerSBCN2012,Bordeaux,France,October23-26,2012I.
KOHLER,J.
SCHAPPLER,T.
SIERRO,J.
-L.
VEUTHEY,S.
RUDAZDispersiveliquid-liquidmicroextractioncombinedwithcapillaryelectrophoresisandtime-of-flightmassspectrometryforurineanalysisAgilentbestposterawardtoI.
KohlerMSB2012,Geneva,Switzerland,February12-13,2012B.
DEBRUS,A.
PERIAT,A.
GRAND-GUILLAUME-PERRENOUD,S.
FEKETE,S.
RUDAZ,D.
GUILLARMEMethodDevelopmentOlympicsattheUniversityofGenevaMostinnovativemethodofdevelopmentprocedure,3rdpriceCoSMoS2012,Providence,RI,USA,September10-12,2012S.
FEKETE,J.
-L.
VEUTHEY,D.
GUILLARMETheeffectofultrahigh-pressureontheretentionpropertiesinRP-HPLC:fromsmalltoverylargeanalytes(biomolecules)Bestposteraward,1stpricetoS.
FeketeISC2012,Torun,Poland,September201230ANNUALREPORT2012ANNUALREPORT201231PHARMACEUTICALBIOCHEMISTRYPPRROOFFEESSSSOORRLeonardoSCAPOZZAMMEERRYogeshvarKALIARREESSEEAARRCCHHAASSSSOOCCIIAATTEESSRemoPEROZZOWilliamBISSONIngoALBERTISSEENNIIOORRRREESSEEAARRCCHHEERRSSLucilePERNOTSCHILTZMagaliZEISSERPPOOSSTTDDOOCCTTOORRAALLSSTTUUDDEENNTTSSCindyBENODAmparoGARCALOPEZCésarSERNAJIMENEZGianpaoloCHIRIANOTaísGRATIERIKiranSONAJESergioDELRIOSANCHOAgataKRANJCPIETRUCCISébastienTARDYSachinDUBEYThomasRIIS-JOHANNESSENPPHH.
.
DDSSTTUUDDEENNTTSSChiaraAMBUEHLPatriciaGRAVENAlessandraMONACOVilmaARMOSKAITEPernillaHOFFMANNIvanaNOVAKOVICMichelaBOI(extra-muros)SemaKADERLISurekhaPIMPLELaraBRAMBILLA(extra-muros)DhavalKALARIAGiuseppinaPISIGNANO(extra-muros)YongCHENMariaLAPTEVALiudasSLEPIKASAndreaCRISTIANILeonardoLAUCIELLOMonicaTESTONI(extra-muros)LauraCURTI(extra-muros)NicoleLONGONI(extra-muros)MariekeVEURINKAADDMMIINNIISSTTRRAATTIIVVEEAANNDDTTEECCHHNNIICCAALLSSTTAAFFFFSylvieGUINCHARDElisaMASSONGiuliaPELLEGRINOBéatriceKAUFMANNOphéliePATTHEYVUADENSOlivierPETERMANNGGEENNEERRAALLDDEESSCCRRIIPPTTIIOONNOOFFTTHHEEUUNNIITTThePharmaceuticalBiochemistrygroupincludestwodistinctfieldsofresearch(http://www.
unige.
ch/sciences/pharm/pb/).
ThefirstisthePharmaceuticalBiochemistry/Chemistryfieldinwhichtheresearchisfocusedonunderstandingligand-macromoleculeinteractionstodevelopnewtherapeuticstrategiesincludingnewchemicalentities,newtargetsusinganinterdisciplinaryapproachbasedonthecombinationofBiochemistry/BiophysicsandChemistrywithComputationalChemistry/MolecularModelling.
Thesecondisinthefieldofdrugdeliveryandfocusesonthetopicalandtransdermaldeliveryoftherapeuticagentsbyinvestigatingtheeffectofmolecularpropertiesonbothpassiveandactivetransportprocesses.
Inaddition,innovativeapproachestoincreasetherangeoftherapeuticagentsthatcanbedeliveredacrosstheskinandsoprovidenewtreatmentoptionsarealsoinvestigated.
32ANNUALREPORT2012SSPPEECCIIFFIICCRREESSEEAARRCCHHFFIIEELLDDSSTheresearchinthefieldofpharmaceuticalbiochemistry/chemistrycoversthreemaintopics,namelyCancer,NeglectedDiseasesandAntibioticsResearch.
InCancerResearchwehavetwomainobjectives,namelythedevelopmentofathymidinekinasebasedsafetyandmonitoringtoolforstemcellstherapyandthedevelopmentofinhibitorsofthetyrosinekinasedomainofoncogenicfusionproteinsinvolvedinsignallingpathways.
WithintheresearchareaofNeglectedDiseasesweaimatelucidatingandvalidatingnewpotentialdrugtargetsagainstthemajorparasiticdiseasesoftheThirdWorlde.
g.
Malaria,TripanosomiasisandLeishmaniosisaswellasfindingpotentialleadcompoundsagainstsuchdiseases.
Theobjectiveofoursinergia-basedantibioticsprojectistofindcompoundsinhibitingbacterialvirulencewithnovelmechanismsofaction.
Inaddition,anewactivityhasrecentlybeeninitiatedtodevelopamolecularrecognition-basedapproachforimprovingantibodyformulation.
Theresearchinthefieldofcutaneousdrugdeliveryincludes:Developmentofnewformulationstoincreaselocalandsystemicbioavailabilityoftopicalandtransdermaltherapeutics.
Investigationoftheinfluenceofphysicochemicalpropertiesonelectrically-assistedtransportacrosstheskin.
Synthesisandcharacterisationofprodrugsoptimisedfortransdermaliontophoreticadministration.
Developmentofnewtechniquesforthenon-invasivedeliveryofbiotechnology-derivedtherapeuticsacrosstheskin("pharmaceuticalbiotechnology").
Evaluationofdermalexposure,riskassessmentandthedevelopmentofpredictivemathematicalmodels.
Investigationofnewtherapeuticapplications.
OOUUTTSSTTAANNDDIINNGGPPUUBBLLIICCAATTIIOONNSSS.
LOVERA,L.
SUTTO,R.
BOUBEVA,L.
SCAPOZZA,N.
DOLKER,F.
L.
GERVASIO.
TheDifferentFlexibilityofC-SrcandC-AblKinasesRegulatestheAccessibilityofaDruggableInactiveConformation.
J.
Am.
Chem.
Soc.
134(5):2496-9,2012.
R.
WEISS,M.
HESSENBERGER,S.
KITZMLLER,D.
BACH,E.
WEINBERGER,W.
D.
KRAUTGARTNER,C.
HAUSER-KRONBERGER,B.
MALISSEN,C.
BOEHLER,Y.
N.
KALIA,J.
THALHAMER,S.
SCHEIBLHOFER.
Transcutaneousvaccinationvialasermicroporation.
JControlRelease,2012;162(2):391-399.
T.
GRATIERI,B.
WAGNER,D.
R.
KALARIA,B.
ERNSTANDY.
N.
KALIA.
TransdermaldeliveryofCGP69669A,asialylLewisxmimetic,acrossintactporcineandhumanskins.
ExpDermatol.
2012,21(3):226-228.
SSPPEECCIIFFIICCPPRROOJJEECCTTSSIINNIITTIIAATTEEDDAANNDDRREECCOOGGNNIITTIIOONNSSSubstrateandinhibitorcomplexesofPlasmodiumfalciparumCa-dependentproteinkinase2(PfCDPK2).
ProposalID20120055,2shiftsof8hoursatthePXIIISynchrotronSLSVilligen,May-August2012,L.
Scapoza,R.
Perozzo,L.
Pernot,LLancellio.
R.
Perozzo,L.
Scapozza.
Phoenixprizeforaninnovativescientificworkinpharmaceuticalchemistry.
October2012Europeanproject:Scafoldsforalternativedelivery(SADEL)(FP7-HEALTH-2011),2012-2016,Euro643'544.
-,L.
Scapozza(PrincipalInvestigator)SNFproject:IdentificationandanalysisoftheputativeAMP-activatedproteinkinase(AMPK)inblood-streamformofTrypanosomabrucei(SNFNo31003A-140722),2012-2015,CHF237'840.
-,R.
Perozzo(PrincipalInvestigator)CRUS-SCIEX:"Newstrategiestoimprovetopicaliontophoreticdeliveryofphotosensitizersforphotodynamictherapy".
Programme2011-2013,CHF70'000,Y.
KALIA(PrincipalInvestigator).
SwissInnovationPromotionAgency.
CTIno.
14416.
1"Developmentofanewalcohol-freegelproductforthecontrolledtransdermaldeliveryoftestosteronetotreatsexualdysfunction"2012-2014,CHF206470(TotalprojectCHF436615)Y.
KALIA(PrincipalInvestigator).
SwissInnovationPromotionAgency.
CTIno.
14334.
1"Peptidesbasedonanimalvenomconstituentsasnewactiveingredientsforcosmeticproducts"2012-2014,CHF194400(TotalprojectCHF565480)Y.
KALIA(Co-Investigator).
UNITEC:"Topical,localizediontophoreticdeliveryofchemotherapyagentsforthetreatmentofheadandneckcancers",Programme2011-12,CHF29800–Y.
KALIA(PrincipalInvestigator).
CCOONNGGRREESSSSEESSOORRGGAANNIISSEEDDL.
SCAPOZZA.
OrganizeroftheUSGEBAnnualMeeting2012entitled"MolecularRecognition:WhenBiologymeetsChemistry"(morethan500participants),6-7February2012,CampusUniversityofLausanne,Lausanne(Switzerland).
W.
BISSON,L.
SCAPOZZA.
OrganizersoftheConferenceentitled"ComputationalChemogenomicstounderstandSystemBiology&ComputationalMedicinalChemistry"(40participants),14-16May,2012,UniversityofGeneva,Geneva(Switzerland).
ANNUALREPORT201233L.
SCAPOZZA.
Co-organizeroftheSymposiumentitled"FortschritteinderPharmakologie:CardiovascularPharmacology"(ca300participants)26.
January2012,Bern(Switzerland)11.
.
PPUUBBLLIICCAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE2244))1.
1SCIENTIFICPUBLICATIONS(WITHIMPACTFACTOR)201.
2SSCCIIEENNTTIIFFIICCPPUUBBLLIICCAATTIIOONNSS((WWIITTHHOOUUTTIIMMPPAACCTTFFAACCTTOORR))11.
3BOOKSCHAPTERS(WITHIMPACTFACTOR)122.
.
PPOOSSTTEERRSSPPRREESSEENNTTAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE2266))2.
1POSTERSPRESENTATIONS2633.
.
OORRAALLPPRREESSEENNTTAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE2288))3.
1CONGRESSES&SYMPOSIA163.
2CONTINUINGEDUCATION&OPENTOTHEPUBLICLECTURES244.
.
TTHHEESSIISSPPRREESSEENNTTEEDD44.
.
11.
.
IINNTTRRAA--MMUURROOSSTTHHEESSIISSDhavalKALARIATransdermalIontophoresisfortheControlledDeliveryofTherapeuticAgentstoTreatNeurodegenerativeDiseases.
UniversityofGeneva–2012–thesisno4480Supervisor:Prof.
LeonardoSCAPOZZACo-supervisor:Dr.
YogeshvarKALIA55.
.
PPUUBBLLIICCRREESSEEAARRCCHHFFUUNNDDSS((FFNNSSRR,,NNIIHH,,CCTTII))SSWWIISSSSNNAATTIIOONNAALLSSCCIIEENNCCEEFFOOUUNNDDAATTIIOONNDevelopmentofPETReporterProbesWithImprovedSensitivityAndSpecificityForInVivoMonitoringofGeneAndCell-BasedTherapyUsingHSV1-tkAsaReporterGeneSNFNo.
31003A-126963/1)Mainapplicant:S.
AMETAMEYCo-applicant:L.
SCAPOZZATotalallocation:CHF288'000.
-Allocation2012:CHF43'200.
-Duration:3yearsStartingdate:1.
9.
2010IdentificationandanalysisoftheputativeAMP-activatedproteinkinase(AMPK)inblood-streamformofTrypanosomabrucei(SNFNo31003A-140722)Mainapplicant:R.
PEROZZOCo-applicant:L.
SCAPOZZATotalallocation:CHF237'840.
-Allocation2012:CHF85'680.
-Duration:3yearsStartingdate:1.
9.
2012IdentificationandcharacterizationofnovelantibacterialcompoundsusingprotozoanhostsSNFNoCRSI33_130016Mainapplicant:L.
SCAPOZZACo-applicants:T.
SOLDATI,P.
COSSON,H.
HILBI,J.
MCKINNEYTotalallocation:CHF1'638'377.
-Allocation2012:CHF554'080.
-Duration:3yearsStartingdate:1.
9.
201034ANNUALREPORT2012DevelopmentofnovelC-5fluoroalkylN-acyclicpyrimidinenucleosideanalogsasPETtracersforinsitumonitoringofgeneandcell-basedtherapiesusingHSV1-TKasareportergene(SCOPESjointresearchproposal,SNFno.
IZ73ZO_127978/1)Mainapplicant:S.
AMETAMEYCo-applicant:L.
SCAPOZZA,S.
RAIC-MALIC,D.
ZAVRSNIKTotalallocation:CHF185'000.
-Allocation2012:CHF60'000.
-(themoneyhasgonetotheeast-europeancountries)Duration:3yearsStartingdate:1.
11.
2009FFOONNDDAATTIIOONNEERRNNEESSTTEETTLLUUCCIIEESSCCHHMMIIDDHHEEIINNYYDemandedesubsidepourl'achatd'undétecteurdemassetriplequadripolaireMainapplicant:Y.
KALIATotalallocation:CHF19'714.
-Allocation2012:CHF19'714.
-CCOOMMMMIISSSSIIOONNAADDMMIINNIISSTTRRAATTIIVVEEDDUURREECCTTOORRAATTDemandedesubsidepourl'achatd'undétecteurdemassetriplequadripolaireMainapplicant:Y.
KALIATotalallocation:CHF61'362.
-Allocation2012:CHF61'362.
-SSEECCRREETTAARRIIAATTDD''EETTAATTAALL''EEDDUUCCAATTIIOONNEETTAALLAARREECCHHEERRCCHHEE((SSEERR))––SSWWIISSSS--IINNDDOOCCOOOOPPEERRAATTIIOONNIINNSSCCIIEENNCCEEAANNDDTTEECCHHNNOOLLOOGGIIEEEEXXEECCUUTTIIVVEEPPRROOGGRRAAMMMMEE.
.
Therapeuticapproachesusingcontrolledtransdermaldeliverytoneurodegenerativeconditionsinagingpopulations(ISJRP123143)Mainapplicant:Y.
KALIATotalallocation:CHF217'810.
-Allocation2012:CHF68'157.
-Duration4yearsStartingdate:1.
6.
2009EEUUFFUUNNDDIINNGGScafoldsforalternativedelivery(SADEL)(FP7-HEALTH-2011)Mainapplicant:L.
SCAPOZZATotalallocation:Euro643'544.
-Allocation2012:CHF254'457.
05Duration5yearsStartingdate:1.
1.
2012IINNNNOOGGAAPPFFUUNNDDIINNGGINNOGAPfundingfromUNITEC#702-A569"Topical,localizediontophoreticdeliveryofchemotherapyagentsforthetreatmentofheadandneckcancers"Mainapplicant:Y.
KALIATotalallocation:CHF29'800.
-Allocation2012:CHF29'800.
-Duration:1yearand6mounthsStartingdate:1.
7.
2011SSCCIIEEXX((SSCCIIEENNTTIIFFIICCEEXXCCHHAANNGGEEPPRROOGGRRAAMMMMEEBBEETTWWEEEENNSSWWIITTZZEERRLLAANNDDAANNDDTTHHEENNEEWWMMEEMMBBEERRSSTTAATTEESSOOFFUUEE))SCIEX10.
012"ECGTOA–InSilicoChemicalGenomicsDrivenDesignandSynthesisofnewantibacterials"Mainapplicant:L.
SCAPOZZATotalallocation:CHF103'000.
-Allocation2012:CHF103'000.
-Duration:1yearand6monthsStartingdate:1.
1.
2011ANNUALREPORT201235SCIEX11.
054CRUS-SCIEX:"Newstrategiestoimprovetopicaliontophoreticdeliveryofphotosensitizersforphotodynamictherapy"Mainapplicant:Y.
KALIATotalallocation:CHF70'000.
-Allocation2012:CHF70'000.
-Duration:1yearStartingdate:1.
2.
2012CCOOMMMMIISSSSIIOONNIINNNNOOVVAATTIIOONNAANNDDTTEECCHHNNOOLLOOGGYY((CCIITT))CTI-14416.
1PFLS-LS:"DevelopmentDevelopmentofanewalcohol-freegelproductforthecontrolledtransdermaldeliveryoftestosteronetotreatsexualdysfunction"Mainapplicant:Y.
KALIATotalallocation:CHF206'470.
-Allocation2012:CHF165'176.
-Duration:2yearsStartingdate:1.
10.
2012CTI-14416.
1FERRING:"DevelopmentDevelopmentofanewalcohol-freegelproductforthecontrolledtransdermaldeliveryoftestosteronetotreatsexualdysfunction"Mainapplicant:Y.
KALIATotalallocation:CHF60'105.
-(IndustrialpartnercontributiontoCTIno.
14416.
1)Allocation2012:CHF60'105.
-Duration:2yearsStartingdate:1.
10.
2012CTI-14334.
1PFLS-LS:"Peptidesbasedonanimalvenomconstituentsasnewactiveingredientsforcosmeticproducts"Mainapplicant:M.
CUENDETCo-applicant:Y.
KALIATotalallocation:CHF194'400.
-Allocation2012:CHF155'520.
-Duration:2yearsStartingdate:1.
10.
2012CTI-14334.
1ACTIVEN:Peptidesbasedonanimalvenomconstituentsasnewactiveingredientsforcosmeticproducts"Mainapplicant:M.
CUENDETCo-applicant:Y.
KALIATotalallocation:CHF27'000.
-(IndustrialpartnercontributiontoCTIno.
14334.
1)Allocation2012:CHF4'000.
-Duration:2yearsStartingdate:1.
10.
201266.
.
RREESSEEAARRCCHHFFUUNNDDSS((IINNDDUUSSTTRRYYAANNDDAASSSSIIMMIILLAATTEEDD))CodeServiceDevelopmentResearchAmountfor2012(CHF)Collaboration1Research40'953.
60Collaboration2Research58'388.
90Collaboration3Research31'590.
00Collaboration4Research39'000.
00Collaboration5Research9'800.
00Collabroation6Research116'217.
04Collaboration7Research35'723.
80Ind-1Research7'502.
17Ind-2Research125'198.
57Ind-3Research25'800.
00Ind-4Research209'949Ind-5Research16'341.
59Ind-6Research6'032.
12722'496.
8036ANNUALREPORT201277.
.
PPAATTEENNTTSSS.
KADERLI,O.
JORDAN,R.
GURNY.
IP:USPatAppl.
61693803(July2012).
S.
KADERLI,R.
GURNY,M.
MLLER,L.
SCAPOZZA.
IPPreliminaryUSPat.
EFSID14508328,(December2012.
)C.
GAMBACORTI-PASSERINI,L.
MOLOGNI,L.
SCAPOZZA,W.
H.
BISSON,P.
GOEKJIAN,S.
TARDY,A.
ORSATO.
Alpha-CarbolinesFortheTreatmentofCancer.
EuropeanPatentApplicationEP12167755,11May2012.
ANNUALREPORT201237PHARMACEUTICALTECHNOLOGYPROFESSEUREricALLEMANNMERFlorenceDELIE-SALMONNorbertLANGERESEARCHASSOCIATESANDLECTURERSPascalFURRERPOSTDOCTORALSTUDENTSAndrejBABICFlorenceMILLERMagdalenaSWIDERSKAAmandineLEFOLLOTECKarineMONDONPH.
DSTUDENTSLutzASMUS*GesineHEUCKJuliePRADALChristianFENCZIoannaMILONAKINawalSEKKATViktorijaHERCEGBénédictePETITNathalieSTRANSKY-HEILKRONCélineXAYAPHOUMMINE(*supervisedbyprof.
R.
gurny)ADMINISTRATIVEANDTECHNICALSTAFFNathalieBOULENSCaroleDUPRAZFlorenceVONOWBrigitteDELAVYMarcoPERDIGAOGENERALPRESENTATIONOFTHEACTIVITYOFUNITSResearchattheunitofPharmaceuticalTechnologyisfocusedonthedeliveryoftherapeuticagentsandcontrastagentsformedicalimagingattherightsiteontherighttime.
EricAllémannhasactivitiesinnanomedicine,energy-activateddrugdeliverysystems,targeted-contrastagentsformedicalimaging.
FlorenceDelieleadsresearchinnanomedicineandvectorization.
NorbertLangeleadsresearchinphotodetection,photodynamictherapyandenzymaticallyactivatedprodrugs.
In2012,variouscollaborationswerecontinuedwiththeUniversityHospitalofGenevaandtheEPFL.
Collaborationprojectswithstart-upcompaniesandestablishedcompanieswereinitiated.
SPECIFICRESEARCHFIELDSThespecificfieldsofresearchare:Developmentofdrugformulationsforintra-articulardeliveryDevelopmentoftreatmentmodalityforstrokebysonothrombolysisEnzymatically-activatedprodrugsandsuparmolecularconstructsDevelopmentfonewcontrastagentsforMRIPolymericphotosenzitizersprojectsImagingofβ-cellsandamyloids38ANNUALREPORT2012OUTSTANDINGPUBLICATIONSM.
F.
ZULAGA,D.
GABRIEL,N.
LANGE.
Enhancedprostatecancertargetingbymodifiedproteasesensitivephotosensitizerprodrugs.
MolPharm,9,1570-1579(2012)PARTICULARPROJECTSINITIATEDIn2012,EricAllémannandNorbertLangestartedtocollaboratewithintheBetaTrainproject(www.
betatrain.
eu).
BetaTrainisaMarieCurieInitialTrainingNetwork(ITN):"EuropeanTrainingNetworkforExcellenceinMolecularImaginginDiabetes".
Itisafour-yearprojectfundedbytheEuropeanCommissionbringingtogether7renownedresearchinstitutesand3privatesectorpartners,eachspecializedindifferentaspectsofbetacell/diabetesimaging.
COLLABORATIONSINITIATEDEricAllémanninitiatedacollaborationwithPharmAlponthedevelopmentofdifferentformulationsforthepreventionandtreatmentofvaginalcandidosis.
1.
((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE3300))PUBLICATIONS1.
1SCIENTIFICPUBLICATIONS(WITHIMPACTFACTOR)171.
2SCIENTIFICPUBLICATIONS(WITHOUTIMPACTFACTOR)12.
POSTERSPRESENTATIONS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE3311))2.
1POSTERSPRESENTATIONS23.
ORALPRESENTATIONS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE3322))3.
1CONGRESSES&SYMPOSIA43.
2CONTINUINGEDUCATION&OPENTOTHEPUBLICLECTURES74.
THESISPRESENTED4.
1INTRA-MUROSTHESISLutzASMUSInjectablesustained-releaseformulationsbasedonpolyestersfromsmallmoleculesolutionstoproteindeliverytotheeyeUniversityofGeneva-thesisn°4403,Co-Directorsofthesis:Prof.
R.
GurnyandDr.
M.
MoellerGesineHEUCKNewstrategiesfortheinductionofendogenousporphyrinsineukaryoticandprokaryoticcellsUniversityofGeneva-thesisn°4415Directorofthesis:N.
Lange5.
RESEARCHFUNDS(FNSR,NIH,CTI)SWISSNATIONALSCIENCEFOUNDATIONPeptidicscaffoldsfortargeteddeliveryofphotosensitizerprodrugsinphotodynamictherapy–(205320-138309/1)Mainapplicant:N.
LangeAllocation2012:CHF0Duration:3yearsStartingdate:2011Noninvasiveinvivoimagingofpancreaticbetacells:developingandtestinginnovativeligandsandMRIcontratsagents–(CR32I3-129987/1)Mainapplicant:P.
MedaCo-applicant:N.
LangeAllocation2012:CHF125'000Duration:3yearsStartingdate:2010ANNUALREPORT201239Protease-sensitivenanoscaledmicellesforthetargeteddeliveryofchemotherapeuticstoprostatecancer–(205321-126834)Mainapplicant:N.
LangeAllocation2012:CHF209'700Duration:3yearsStartingdate:2010AmyloidpeptidegraftedtoGd-nanoparticlesforamyloidosisdiagnosis–(31NM30_141416/1)Mainapplicant:X.
Montet(CMU)Co-applicant:E.
AllémannAllocation2012:CHF98'125Duration:3yearsStartingdate:20126.
RESEARCHFUNDS(INDUSTRYANDASSIMILATED)CodeServiceDevelopmentResearchAmountfor2012(CHF)OMService10'200VIROBLOCKService5'000TRBService20'000PHARMALPResearch12'500DEBIOService1'500BRACCOService6'000SWISSMEDICService6'00061'20040ANNUALREPORT2012ANNUALREPORT201241PHARMACOCHEMISTRYPPRROOFFEESSSSOORRPierre-AlainCARRUPTRREEAADDEERRSSDavyGUILLARMERREESSEEAARRCCHHAASSSSOOCCIIAATTEESSSophieMARTELSSEENNIIOORRRREESSEEAARRCCHHEERRSSClaudiaAVELLOSIMOESPIRESJuliettaGRADINARUAlessandraNURISSO(since1.
8.
2012)AntoineDAINAPPOOSSTTDDOOCCTTOORRAALLSSTTUUDDEENNTTSSAlessandraNURISSO(until31.
7.
2012)AlessandraZIZZARIPPHH.
.
DDSSTTUUDDEENNTTSSAlbanBUJARDCélineLEBOURDONNEC-PASSELEULucieRYCKEWAERTSarraDEVALENCENilsOBERHAUSERLionelSACCONNAYPhilippeEUGSTERCharlottePETITKarineVUIGNIERElisabethFAVREStephanieROMANDVincentZWICKCCOO--TTUUTTEELLLLEECeciliaFORTUGNOAADDMMIINNIISSTTRRAATTIIVVEEAANNDDTTEECCHHNNIICCAALLVirginieBEYELER(apprentielaborantine)FabriceGILLERATSylviaPASSAQUAY-RIONChristopheFRANCEYIrenaNIKOLOVAEmilieREGINATOGGEENNEERRAALLDDEESSCCRRIIPPTTIIOONNOOFFTTHHEEUUNNIITTTheteamofpharmacochemistrydevelopedoriginaltheoreticalandexperimentalmethodsabletoquantifyintermolecularinteractionsofadrugwithitsbiologicalpartnerssuchastherapeutictargetsorbiologicalmembranes.
Thisresearchintendedtoacceleratethediscoveryofchemicalcompoundsoftherapeuticinterestandtooptimizetheeffectiveness,theselectivityandthesafetyoftheselecteddrugcandidates.
TheywerecenteredonthedevelopmentandvalidationofinsilicoandinvitroHTSfilterstocharacterizephysicochemicalproperties,passivemembranepermeationandcellulareffluxofnewchemicalentities.
VirtualandinvitroHTSscreeningapproacheswereoptimizedtostudytheinteractionswithsomespecificbio-targetsinvolvedinneurodegenerativediseaseslikeAlzheimerandParkinson'sdiseasesweremeasuredinordertoidentifymultifunctionaldrugcandidates.
42ANNUALREPORT2012SSPPEECCIIFFIICCRREESSEEAARRCCHHFFIIEELLDDSSBiochemicalscreening:enzymeInhibition;antioxidantprofilingofNCEs;antiapoptoticpropertiesofNCEs;enzymatichydrolysisofdrugsandprodrugs;inhibitionofhERGchannel;inhibitionofHDACandSIRTproteins.
Molecularmodelling:Intermolecularinteractionfields;indirectmolecularmodelling;directmolecularmodelling;quantumchemistry.
Physicochemicalscreening:Physicochemicalprofiling;antioxidantproperties.
Permeationscreening:passivepermeationprofilingusingPAMPA-membranestomimictheskin,theintestinalbarrierandtheblood-brainbarrier.
3D-QSARmodelsassociatedwithproteinsresponsibleofcellulareffluxinmembranepermeationormulti-drugresistance.
OOUUTTSSTTAANNDDIINNGGPPUUBBLLIICCAATTIIOONNSSA.
NURISSO,C.
SIMOES-PIRES,S.
MARTEL,D.
CRESSEND,A.
GUILLOT,PA.
CARRUPT.
HowtoincreasesafetyandefficacyofcompoundsagainstneurodegenerationAmultifunctionalapproach.
Chimia,66:286-290,2012.
K.
VUIGNIER,JL.
VEUTHEY,PA.
CARRUPT,J.
SCHAPPLER.
Characterizationofdrug-proteininteractionsbycapillaryelectrophoresishyphenatedtomassspectrometry.
Electrophoresis,33:3306-3315,2012.
L.
SACCONNAY,MPB.
SOARES,D.
SMIRLIS,E.
F.
QUEIROZ,JL.
WOLFENDER,PA.
CARRUPT,A.
NURISSO.
Towardanovelhigh-throughputscreeningassaybasedonPAMPA-GITtodetectpotentialinteractionwithP-Glycoprotein.
Chimia,666:346,2012.
SSPPEECCIIFFIICCPPRROOJJEECCTTSSIINNIITTIIAATTEEDDAANNDDRREECCOOGGNNIITTIIOONNSSThebindingmodestudyofseveralreportedTollLikeReceptor4/MD2modulatorsbymeansofdockingtechniques,especiallywiththeuseofMLPToolsrecentlydevelopedinourresearchgroup,withtheaimofdesigningnewligandsandelucidatingthemechanismatatomicdetail.
ThevirtualscreeningofnaturalcompoundsontheRNAdependentRNApolymeraseofHepatitisCviruswiththeaimofisolatingnewactivecompoundsandproposingstructuralmodificationsforincreasingaffinityandefficacy.
CCOOLLLLAABBOORRAATTIIOONNSSIINNIITTIIAATTEEDDWithS.
M.
SANTAMARIA(UniversitySanPabloCEUMadrid)WithA.
BOUMENDJEL(UniversityofGrenoble)WithM.
CUENDET(UniversityofGeneva)11.
.
PPUUBBLLIICCAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE3344))1.
1SCIENTIFICPUBLICATIONS(WITHIMPACTFACTOR)1522.
.
PPOOSSTTEERRSSPPRREESSEENNTTAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE3355))2.
1POSTERSPRESENTATIONS1233.
.
OORRAALLPPRREESSEENNTTAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE3366))3.
1CONGRESSES&SYMPOSIA1044.
.
TTHHEESSIISSPPRREESSEENNTTEEDD44.
.
11.
.
IINNTTRRAA--MMUURROOSSTTHHEESSIISSElisabethFAVREInsilicostudiesoftyrosinases:structuresandinteractions.
UniversityofGeneva–2012Supervisor:ProfPierre-AlainCARRUPTKarineVUIGNIERAnalyticalstrategytocharacterizedrug-proteininteractions:fromhighthroughputtoin-depthanalysis.
UniversityofGeneva–2012Supervisor:Prof.
Pierre-AlainCARRUPTCristinaPOMILIO(TesidiLaurea)Liposomalformulationsofantiparkinsonagents:studyofpassivediffusionusingaPAMPA-BBBmodelUniversityofChieti–2012Supervisor:Prof.
Pierre-AlainCARRUPTANNUALREPORT20124355.
.
PPUUBBLLIICCRREESSEEAARRCCHHFFUUNNDDSS((FFNNSSRR,,NNIIHH,,CCTTII))CCTTIIEstablishmentofapredictivemodelforchemicalpermeationacrossthehumanairwayepitheliuminvitrousingMucilAirTM(No14000.
1PFLS-LS).
Mainapplicant:EPITHELIXCo-applicant:P.
A.
CARRUPTTotalAllocation:CHF242'027.
-Allocation2012:CHF128'849.
-Duration:18moisStartingDate:201266.
.
RREESSEEAARRCCHHFFUUNNDDSS((IINNDDUUSSTTRRYYAANNDDAASSSSIIMMIILLAATTEEDD))CodeServiceDevelopmentResearchAmountfor2012(CHF)Indu-149'936.
-Indu-24'200.
-Indu-34'000.
-Indu-43'600.
-Indu-51'282.
-63'018.
-44ANNUALREPORT2012ANNUALREPORT201245PHARMACOGNOSYPROFESSORMurielCUENDETMERPhilippeCHRISTENSENIORRESEARCHERSClaudiaAVELLOSIMOESPIRESPOST-DOCTORALSTUDENTSAminaHAOUALAAndreasNIEVERGELT-MEIERPH.
D.
STUDENTSOlivierCICLETMarkISSAVincentZWICKMélanieHOERLECarolineMATHONADMINISTRATIVEANDTECHNICALSTAFFMartineCABONatalieSCHREGLEGENERALDESCRIPTIONOFTHEUNITTheteamofpharmacognosyisfocusedonthediscoveryofbioactivenaturalproducts.
Compoundswithcancerchemopreventiveandantimalarialactivityareofparticularinterest.
Intheseareas,thedevelopmentofnewandbetterdrugsremainsaprincipalneed.
Asestablishedbyampleprecedent,natureprovidesbroadchemicaldiversity.
Preventioniswelldevelopedinthefieldofcardiovasculardisease,butsimilardrugsthatcouldpreventcanceronthisscalearestillalongwayoff.
Apanelofinvitrobioassaysindicativeofinhibitingmajorstagesofcarcinogenesis(initiation,promotionandprogression)isused.
Also,antimalarialdrugsavailableonthemarkethavealimitedefficacyandstrongsideeffects.
Someplantextractshavingshowngoodinvitroandinvivoactivityarecurrentlybeinginvestigatedtouncoverthecompoundsresponsiblefortheactivityandtheirmechanismofaction.
Theabsorptionandthemetabolismofpurecompoundsandphytopreparationsarealsobeingevaluatedinvitroandinvivo.
Anotherareaofinterestistheappearanceofbotanicalpreparationsonthemarketwithmedicinalclaimswhichescapetoregistrationbecausetheyarevoluntarilysoldasconventionalfoodderivedproducts.
Nowadays,suchherbalremediesaresoldinhealthfoodstores,supermarketsorovertheinternetwithoutseriouslyquestioningtheirpotentialactivity,sideeffectsortoxicity.
Furthermore,thereisamisconceptionandgeneralbeliefthattheseplantderivedpreparationsarenaturalandthereforeareperceivedas"safe",regardlessofpotentialdangers.
Thusthereisanurgentneedtoassessthesafetyofbotanicalsandestablishacompendiumofbotanicalingredientswhichmaybeofhealthconcernswhenusedinfoodderivedproducts.
Tosupportfoodsafetyauthorities,adequatescreeningapproachesandanalyticalmethodsarebeingdevelopedtoprovidechemicalevidenceofthepresenceofanundesiredbotanicalortoxicant.
Theauthenticityoftheingredientsisalsochecked.
46ANNUALREPORT2012SPECIFICRESEARCHFIELDSCancerchemopreventivescreeningofnaturalproducts:quinonereductaseinduction,HDACinhibition,andanti-inflammatoryactivityAntimalarialactivityActivity-guidedfractionationAbsorptionandmetabolizationstudiesofphytopreparationsandpurenaturalproductsusingCaco-2cellsandaratinvivomodelIndepthstudiestouncoverthemechanismofactionofpurenaturalproductsandphytopreparationsDevelopmentofaLC-MS/MSmethodabletoscreensimultaneouslyfor62specieswhosepresenceinfoodmightbeproblematicCONGRESSESProf.
MurielCuendetandProf.
Jean-LucWolfenderweretheorganizersofthe27thSeminarinPharmaceuticalSciencesinZermatt,Switzerland,inSeptember2012,DrugsfromNature:fromDiscoverytoClinic.
Prof.
MurielCuendetwastheorganizeroftheWG3COSTmeeting(COSTTD0905,Epigenetics–BenchtoBedside),11September,2012,Geneva(Switzerland).
OUTSTANDINGPUBLICATIONSS.
M.
AL-MASSARANI,S.
BERTRAND,A.
NIEVERGELT,A.
M.
EL-SHAFAE,T.
A.
AL-HOWIRINY,N.
M.
AL-MUSAYEIB,M.
CUENDET,J.
-L.
WOLFENDER.
AcylatedpregnaneglycosidesfromCarallumasinaica.
Phytochemistry,79,129-140.
2012.
C.
MATHON,M.
DURET,M.
KOHLER,P.
EDDER,S.
BIERI,P.
CHRISTEN.
Multi-targetedscreeningofbotanicalsinfoodsupplementsbyliquidchromatographywithtandemmassspectrometry.
FoodChemistry,138(1),709-717.
2012.
1.
PUBLICATIONS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122--PPAAGGEE3388))1.
1SCIENTIFICPUBLICATIONS(WITHIMPACTFACTOR)62.
POSTERSPRESENTATIONSDDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE3399))(2.
1POSTERSPRESENTATIONS43.
((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE3399))ORALPRESENTATIONS3.
1CONGRESSES&SYMPOSIA53.
2CONTINUINGEDUCATION&OPENTOTHEPUBLICLECTURES13.
3RADIO/TELEVISIONINTERVENTION14.
PUBLICRESEARCHFUNDS(FNSR,CTI,ETC…)MMVArgemoneMexicanaMMV11/0003–MedicinesforMalariaVentureApplicants:P.
CHRISTENandM.
CUENDETTotalallocation:CHF289'505.
32Allocation2012:CHF89'598.
79Duration:3yearsStartingdate:2011FNSRFunctionalgenomeanalysisinageneticallyintractablesystem:aninterdisciplinaryproof-of-conceptstudySUBSIDECRSII3-141837MainapplicantofP2:M.
CUENDETTotalallocation:CHF335'016.
—Allocation2012:CHF79'680.
—Duration:3yearsStartingdate:2012ANNUALREPORT201247EvaluationofthehealthbenefitsofBrazilianfruitsandvegetablesforthedevelopmentofsafeandvaluablefunctionalfoodsBrazilianSwissJointResearchProgram–BSJRPApplicants:J.
-L.
WOLFENDER,M.
CUENDET,E.
FERREIRA-QUEIROZ.
Totalallocation:CHF173'400.
—Allocation2012:CHF112'000.
—Duration:2yearsStartingdate:2012CTIPeptidesbasedonanimalvenomconstituentsasnewactiveingredientsforcosmeticproductsCTI-Projet14334.
1PFLS-LSMainapplicant:M.
CUENDETCo-applicant:Y.
KALIATotalallocation:CHF194'400.
—Allocation2012:CHF155'520.
—Duration:2yearsStartingdate:2012PeptidesbasedonanimalvenomconstituentsasnewactiveingredientsforcosmeticproductsCTI-Projet14334.
1ACTIVENMainapplicant:M.
CUENDETCo-applicant:Y.
KALIATotalallocation:CHF27'000.
—Allocation2012:CHF4'000.
—Duration:2yearsStartingdate:2012EUFUNDINGIntegratedtechnologiesforthediscoveryanddevelopmentofcosmeceuticalagentsfromplantbiodiversityNATPROTECIAPP-MarieCurieMainapplicant:M.
CUENDETCo-applicant:J.
-L.
WOLFENDERTotalallocation:CHF263'225.
23(222'131.
—)Allocation2012:CHF59'400.
51Duration:4yearsStartingdate:20125.
RESEARCHFUNDS(INDUSTRYANDASSIMILATED)CodeServiceDevelopmentResearchAmountfor2012(CHF)FondsIndustrie(J.
L.
Wolfender,M.
Cuendet,Ph.
Christen)Research&Services90'712.
--48ANNUALREPORT2012ANNUALREPORT201249PHARMACOLOGYPROFESSORUrsT.
RUEGGSENIORRESEARCHERSOlivierDORCHIESPOSTDOCTORALSTUDENTSKarinJACOBSON-JOHANSSONMiriamKOVACS-STROSOVAJuliePATTE-REUTENAUERPH.
D.
STUDENTSHeshamMOHAMEDISMAILADMINISTRATIVEANDTECHNICALSTAFFDominiqueHUNZIKEROphéliePATTHEY-VUADENSOlivierPETERMANNColetteSAUTY-DEFFERARDGENERALDESCRIPTIONOFTHEUNITOurprojectsaimtoidentifynewtherapeutictargetsintheareaofmuscledisordersinordertofindnoveltreatments.
Focusisontreatmentofmusculardystrophy,inparticularDuchennemusculardystrophy(DMD).
DMDisoneofthemostcommonhereditarydiseasesofchildhoodleadingtoprogressiveweakness,lossofwalkingabilityduringthefirstdecadeoflife,withdeathoccurringusuallyatage20to30.
Themolecularbasisofthisdiseaseischaracterizedbytheabsenceofdystrophin,alargeproteininthecytosolofthecell.
Mutationsofthedystrophingene,locatedontheXchromosome,causemuscledegenerationinhumansandinmdxmice,amousemodelofDMD.
Eventhoughthegene-withits200ormoremutations-andtheresultingproteinproductsarewellknown,thefunctionalroleofdystrophinhasnotyetbeencompletelyelucidated.
Inparticular,itisnotclearwhytheabsenceofdystrophinhasdramaticconsequencesonthepatients.
Affectedpatientsaretreatedinasymptomaticway,mostoftenwithglucocorticoids;theseincreaselifeexpectancybutdonotimprovethelong-termoutcome.
Recenttherapeuticeffortshavefocusedonreplacementoftheprimarygeneticdefectbygene-transferorstemcelltherapy,oronitscorrectionviatheexon-skippingapproach.
Resultssuggestcautiousoptimism.
Weareoftheopinionthataneffectivecurativetreatmentwillbeavailableatbestin10-30yearsandwillbeverycostly.
Thus,pharmacologicalapproachesarejustifiedforthebenefitofboth,patientsandtheirparents.
Cellularandmolecularassays,inparticularthoselinkedtocalciumchannels(electrophysiology,calciumimagingviafluorescence),muscleforceassayandhistology.
Weproceedfromcelllines(ofmurineandhumanorigin)topurifiedmyotubes,primarymyotubecultures,tofreshlyisolatedfibersandfinallytomiceinordertoverifyimportantinvitrofindings.
Thetechniquesappliedattheinvitrolevelincludegenedeletionandoverexpression,Ca2+influxandimagingaswellaselectrophysiologicalstudiescombinedwithexposuretopharmacologicalagentstodeterminepathwaysandendpointssuchascell/fibersurvivalorapoptosis.
Invivoexperimentsoncontrolanddystrophicmicearedesignedinawayallowinginvestigationsoftissuequality,muscleforceandrecoveryfromtetanus,assessmentofbiomarkersandoftheskeletonbywholebodyX-raytomography.
SPECIFICRESEARCHFIELDSWe,andothers,havefoundthatmusclecellsfromDMDpatients,orfrommdxmice,displayabnormallyelevatedcalciuminfluxleadingtoanincreaseincytosoliccalciumconcentrationswhenthesecellsareexposedtomechanicaloroxidativestress.
Itislikelythatthistriggersthedeathofmusclecells.
Inmostcases,ourresultsshowthatnormalizingthiscalciumderegulationinmdxmusclecellsorfiberswiththeuseofdrugsalsoimprovesthemusclefunctionofthesemice.
InvestigationsbyothersshowthatNADPHoxidasesarethemajorproducersofoxidativestress,thattheseproducean50ANNUALREPORT2012excessiveamountofstress,namelysuperoxideanionradical,amajorcomponentofoxidativestress,andthatthedownstreamtargetsarestore-operatedcalciumchannels.
RECENTRESULTS:Glucocorticoidsimprovethequalityofdystrophicmusclebutcauseatrophyinnormalmuscle;however,themechanismsarenotwellunderstood.
Wefoundthatglucocorticoidsinhibitstress-inducedcalciumentryintomdxmusclecells.
ItisknownthatlysophospholipidsproducedbyaparticularisoformofphospholipaseA2(iPLA2)leadtotheactivationofstore-operatedcalciumchannels.
Usingpatch-clampandcalciumimagingtechnology,wefoundthatinhibition,ordown-regulation,ofiPLA2preventstheactivationofstore-operatedchannels.
WefoundthatiPLA2isoverexpressed2-3-foldinmdxmuscleattheageof4-8weekswhentherateofnecrosisishighest.
SimilarfindingsweremadeinDMDboyswhoseiPLA2levelswere10-20-foldhigheratage3to5years.
SuchelevatedlevelsofiPLA2willproducehigheramountsoflysophospholipids(cf.
point2),whichwouldactivatestore-operatedchannels.
Thiscascadeofeventscouldbetheunderlyingreasonfortheincreasedcalciumentryintodystrophicmuscle.
Inaddition,wefoundthatmdxmusclescontain6-timeslessofthePLA2-inhibitorannexin-1,thusfacilitatinglysophospholipidproduction.
Consistentwiththefactthatexpressionlevelsofannexin-1areknowntobeupregulatedbyglucocorticoids,wefoundthattheglucocorticoidreceptoragonistprednisoloneincreasedexpressionofthisinhibitortwo-foldindystrophicmyotubes.
Store-operatedcalciumchannelsareformedbyOrai1andTRPV2proteinsbutnotbyTRPC1,asshownbyourinvestigationsonTRPC1k/omdxhybridmice.
Wefoundthatpolyphenolsfromgreentea,inparticularthemajorconstituent,epigallocatechingallate,haveabeneficialeffectonthemuscleofmdxmice.
Thesecompoundsalsoreducetheelevatedcalciuminfluxintodystrophicmuscleandconsequentlynormalizethecytosoliccalciumlevels.
AclinicaltrialusingepigallocatechingallateinDMDboyshasbeeninitiatedatCharitéHospitalinBerlin.
Recently,wefoundthattamoxifen,apartialagonistattheestrogenreceptor,givenorallyat10mg/kg/dayfor15monthstomdxmice,ledtoenhancedmuscleforceandresistancetofatigue,decreasedfibrosisofthediaphragm,andreducedplasmacreatinekinaselevels.
Agridtestrevealedthatthesamedoseoftamoxifengivenfor10weeksto6month-oldmdxmiceledtoanameliorationoftheirperformance,suchthatafteraboutfourweeks,scoresidenticaltothoseofwild-typemicewereattained.
Furthermore,tamoxifenincreasedthespontaneouslocomotoractivityofthesemdxmicetonear-normalvalues,fullynormalizedthephasictension,andcorrectedby~65%thetetanictensiondeficitthatwasfoundbetweennormalanddystrophictricepssuraemuscle.
Inaddition,theproportionofEvansblue-permeablefibersdecreased~2.
5-foldinthediaphragmoftreateddystrophicmicecomparedtountreatedones.
Importantly,mosteffectsoftamoxifenwereevidentevenatthelowestdosetested(0.
1mg/kg/day).
Thisdoseissimilarto,orbelow,theoneprescribedforpatientssufferingfrombreastcancer,andcorrespondstoabout10timeslessthanthedoseofprednisolonerequiredtoelicitsomeimprovementofthedystrophicphenotypeinhumans.
Althoughmoreinvestigationsarerequired,tamoxifenisapromisingcandidateforclinicaltrialssinceithasalreadybeenapprovedforotherindications,hasbeenwidelyusedinpatientsformanyyears,isreadilyavailable,andhasanacceptablesafetyprofilewithgenerallyfewside-effectsatlowdoses.
OUTSTANDINGPUBLICATIONSJ.
REUTENAUR-PATTE,F.
X.
BOITTIN,O.
PATTHEY-VUADENS,U.
T.
RUEGG,O.
M.
DORCHIES,UrocortinsimprovedystrophicskeletalmusclestructureandfunctionthroughbothPKA-andEpac-dependentpathways.
AmJPathol.
(Epub2012),180:Y.
NAKAE,O.
M.
DORCHIES,P.
J.
STOWARD,B.
F.
ZIMMERMANN,U.
T.
RUEGG,Quantitativeevaluationofthebeneficialeffectsinthemdxmouseofepigallocatechingallate,anantioxidantpolyphenolfromgreentea.
HistochemCellBiol.
137,811-27(2012).
N.
ITO,U.
T.
RUEGG,A.
KUDO,Y.
MIYAGOE-SUZIKI,S.
TAKEDA,ActivationofcalciumsignalingthroughTrpv1bynNOSandperoxynitriteasakeytriggerofskeletalmusclehypertrophy.
NatMed.
19:101-6.
Epub(2012)Dec2.
doi:10.
1038/nm.
3019.
COLLABORATIONSINITIATEDCharitéMedicalUniversityBerlinandMaxDelbrueckCenterforMolecularMedicine,Berlin,D-13125,GermanyDepartmentofBasicMedicalSciences,UniversityofArizonaCollegeofMedicine,Phoenix,Arizona85004-USA1PUBLICATIONSDDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE4400))(1.
1SCIENTIFICPUBLICATIONS(WITHIMPACTFACTOR)41.
2SCIENTIFICPUBLICATIONS(WITHOUTIMPACTFACTOR)11.
3BOOKCHAPTER12.
POSTERSPRESENTATIONS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE4411))2.
1POSTERSPRESENTATIONS3ANNUALREPORT2012513.
ORALPRESENTATIONSDDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE4411))(3.
1CONGRESSES&SYMPOSIA53.
2CONTINUINGEDUCATION&OPENTOTHEPUBLICLECTURES14.
PUBLICRESEARCHFUNDS(FNSR,NIH,CTI)ASSOCIATIONFRANAISECONTRELESMYOPATHIESEssaipré-cliniquesurletraitementdelamyopathiedeDuchenneparletamoxifèneApplicant:U.
T.
RueggAllocation2012:CHF68'000Duration:2yearsStartingdate:01.
03.
2011DUCHENNEPARENTPROJECT,NLInvestigationofthebeneficialeffectsoftamoxifenindystrophicmuscleApplicant:U.
T.
RueggAllocation2012:CHF57'500Duration:3yearsStartingdate:1.
01.
2010SWISSNATIONALSCIENCEFOUNDATIONApharmacologicalstrategytotreatDuchenneMuscularDystrophy–No.
3100-122548/2Mainapplicant:U.
T.
RueggAllocation2012:CHF53'545Duration:4yearsStartingdate:1.
01.
200952ANNUALREPORT2012ANNUALREPORT201253PHYTOCHEMISTRYANDBIOACTIVENATURALPRODUCTSPROFESSORJean-LucWOLFENDERMEREmersonFERREIRA-QUEIROZSENIORRESEARCHERSElisabethRIVARA-MINTENGuillaumeMARTIPOST-DOCTORALSTUDENTSSamuelBERTRANDLiseBREANTFlorenceMEHLPH.
D.
STUDENTSNadineBOHNISouraCHALLALAdelineCHAUVINVéraOLDRATIPhilippeEUGSTERQuentinFAVRE-GODALDanielMAAGADMINISTRATIVEANDTECHNICALSTAFFLaurenceMARCOURTKarineNDJOKOIOSETNatalieSCHREGLEGENERALDESCRIPTIONOFTHEUNITThemainresearchactivitiesoftheunitarerelatedtothedevelopmentofmethodologiesfortherapidisolationidentificationandbioactivitycharacterisationofnaturalproducts(NPs)atthemicrogramscale.
State-of-the-artLC-MSandLC-MS/MSaswellasmicroNMRtechniquesareusedfordereplicationpurposesordenovoidentificationofNPsincrudeextractsfromdifferentorigins(plants,fungi,andmicroorganisms).
Microfractionationmethodsin96wellplatesallowbioassaystobeperformedonLCpeakincrudeextracts,quantitativeestimationofthewellcontentandfurtherstructuraldeterminationbyCapNMR.
RationallargescaleisolationstrategiesaredevelopedfortherapidobtentionofpureNPsinthemgscaleforfurthertestingbioactiviesandmodeofaction.
Therangeofbiologicalactivititiesstudiedinhouseorincollborationcoversmainlyantifungal,antiprotozoal,antiinflammatoryandantiepilepticactivities.
Theinterestofthegroupisalsofocusedonplantmetabolomics,inthisrespectthefocusisontheinvestigationofbioactiveNPsdynamicallyinducedinvariousstresssituations(fungiconfrontation,bioticandabioticstresses,metaboliteelicitation…).
WiththeideatogenerateorginalsourcesofbioactiveNPsotherstrategiesincludingbiotransformationorchemicalderivatisationofcrudeextractsfromcommonsourcesarealsoinvestigated.
Finallytheanalyticalandmetabolomicmethodsarealsousedforstudyingthemetabolisationofcrudeextractsinviewofabetterunderstandingofthemodeofaction(synergy,prodrugs)andthepotentialtoxicityofphytopharmaceuticalsornutraceuticals.
SPECIFICRESEARCHFIELDSSearchfornewleadcompoundsfromnaturalsourcesOn-lineidentificationofnaturalproductsbyLC-UV-NMR-MS(dereplication)RapidmicrofractionationofcrudeextractsforchemicalandbioactivityprofilingPlantmetabolomicsSearchfororiginalbioactivestress-inducednaturalproductsofvariousoriginStudyofantifungalcompoundsfrompathogenfungiinco-cultureQualitativequantitativeanalysisofphytotherapeuticals54ANNUALREPORT2012StudyofthemetabolisationofphytopreparationbymetabolomicsinrelationwiththeirmodeofactionInvestigationofnaturalproductsinvolvedindiseasesassociatedwithproblemsofageingSearchfornewleadcompoundsforuseagainsttropicalparasiticdiseasesCONGRESSESProf.
Jean-LucWolfenderandProf.
MurielCuendetweretheorganizersofthe27thSeminarinPharmaceuticalSciencesinZermatt,Switzerland,inSeptember2012,DrugsfromNature:fromDiscoverytoClinic.
AsPresidentoftheccCTA(CentreofCompetenceinToxicologicalandAnalyticalChemistry,Prof.
Jean-LucWolfenderwasresponsiblefororganisationofthe"GrandPublic"ConferencefromtheccCTA,atthe"InstitutNationalGenevois"inGeneva,Switzerland,inMarch2012:ArtetChimieAnalytique.
AsmemberofthelocalprogramadvisoryboardfromMSB,Prof.
Jean-LucWolfenderwasoneoftheorganizersofthe27thInternationalSymposiumonMicroScaleBioseparationsandAnalysis(MSB2012)inGeneva,Switzerland.
OUTSTANDINGPUBLICATIONSS.
M.
AL-MASSARANI,S.
BERTRAND,A.
NIEVERGELT,A.
M.
EL-SHAFAE,T.
A.
AL-HOWIRINY,N.
M.
AL-MUSAYEIB,M.
CUENDET,J.
-L.
WOLFENDER.
AcylatedpregnaneglycosidesfromCarallumsinaica.
Phytochemistry,79:129-140,2012P.
J.
EUGSTER,D.
BIASS,D.
GUILLARME,P.
FAVREAU,R.
STCKLIN,J.
-L.
WOLFENDER.
PeakcapacityoptimisationforhighresolutionpeptideprofilingincomplexmixturesbyLiquidChromatographycoupledtoTime-of-FlightMassSpectrometry:ApplicationtotheConusconsorsconesnailvenom.
J.
Chromatogr.
A,1259:187-199,2012.
C.
S.
FUNARI,P.
J.
EUGSTER,S.
MARTEL,P.
-A.
CARRUPT,J.
-L.
WOLFENDER,D.
H.
S.
SILVA.
Highresolutionultra-highpressureliquidchromatography-time-of-flightmassspectrometrydereplicationstrategyforthemetaboliteprofilingofBrazilianLippiaspecies.
J.
Chromatogr.
A,1259:167-178,2012.
J.
-L.
WOLFENDER,S.
RUDAZ,Y.
H.
CHOI,H.
K.
KIM.
PlantMetabolomics:FromHolisticDatatoRelevantBiomarkers.
Curr.
Med.
Chem.
,20:1056-1090,2012.
1.
PUBLICATIONS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE4422))1.
1SCIENTIFICPUBLICATIONS(WITHIMPACTFACTOR)132.
POSTERSPRESENTATIONS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE4433))2.
1POSTERSPRESENTATIONS243.
((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE4455))ORALPRESENTATIONS3.
1CONGRESSES&SYMPOSIA313.
2CONTINUINGEDUCATION&OPENTOTHEPUBLICLECTURES53.
3RADIO/TELEVISIONINTERVENTION14.
PUBLICRESEARCHFUNDS(FNSR,NIH,CTI)NCRRNCCRPlantSurvivalWP2,plantsantagonistsandmutualists(N°110-108)Mainapplicant:T.
TURLINGS,UNINECo-applicants:J.
L.
WOLFENDERTotalallocation:CHF169'000.
--Allocation2012:CHF36'670.
--Duration:4yearsStartingdate:2009ANNUALREPORT201255SWISSNATIONALSCIENCEFOUNDATIONFusariuminhumanandplantpathology:Investigationofphytoalexinsandmycoalexinswithfungitoxicactivityforthesearchofnewantifungalagentsandcharacterisationofcommontraits(CRSII3_127187/1)Mainapplicant:J.
L.
WOLFENDERCo-applicant:M.
MONOD,CHUV,K.
GINDROandS.
SCHRCH,ACWAllocation2012:CHF251'369.
--Duration:3yearsStartingdate:2009TargetedandmetabolomicstudyoftheearlychemicaleventsofthewoundresponseinA.
thaliana:dynamicsofsignalingandsearchforlongdistancebiomarkers(No205320/135190–1)Applicant:J.
L.
WOLFENDERCo-applicant:S.
RUDAZCo-applicant:T.
FARMER,UNILTotalallocation:CHF130'620.
--Allocation2012:CHF66'660.
--Duration:2yearsStartingdate:2011SINOSWISSSCIENCEANDTECHNOLOGYCOOPERATION–SSSTCCollaborationbetweentheSchoolofPharmaceuticalSciencesoftheUniversityofShandongandGenevaSinoSwissScienceandTechnologyCooperationProgram(SSSTC)IP18-092011Mainapplicant:J.
L.
WOLFENDERTotalallocation:CHF31'100.
--Allocation2012:CHF7'800.
--Duration:3yearsStartingdate:2012SECRETARIATD'ETATAL'EDUCATIONETALARECHERCHE(SER)EvaluationoftheHealthBenefitsofBrazilianFruitsandVegetablesfortheDevelopmentofSafeandValuableFunctionalFoodBrazilianSwissJointResearchProgram-BSJRPApplicants:J.
L.
WOLFENDER,M.
CUENDET,E.
FERREIRA-QUEIROZTotalfunding:CHF173'400.
--Totalallocation:CHF112'000.
--Allocation2012:CHF53'000.
--Duration:2yearsStartingdate:2012FP7-PEOPLE-IRSES/IAPP-EUROPEANGRANTExploringChemicalBiodiversitywithInnovativeApproachesforFightingChagasandLeismaniasisProposalN°269301–acronym:ChemBioFight:Applicant:L.
SKALTSOUNIS(EUCoord)Co-Applicant:J.
L.
WOLFENDER(CHCoord.
)Othercountries:GRC,FRA,NLD,BRA,ARG,CHITotalallocation:Euros434'700.
—Allocation2012:0.
--Duration:4yearsStartingdate:2011IntegratedTechnologiesfortheDiscoveriyandDevelopmentofCosmeceuticalAgentsfromPlantBiodiversityProposalNo286287–acronym:NATPROTECApplicant:L.
SKALTSOUNIS(EUCoord.
)Co-Applicant:M.
CUENDET(CHCoord.
),UNIGECo-applicant:J.
L.
WOLFENDEROthercountries:GRC,FRA,AUSTotalfunding:Euros1'813'624.
—Allocation2012:Euros50'118.
—(CHF59'400.
--)Duration:4yearsStartingdate:201256ANNUALREPORT20125.
RESEARCHFUNDS(INDUSTRYANDASSIMILATED)CodeServiceDevelopmentResearchAmountfor2012(CHF)FondsIndustrie(J.
L.
Wolfender,S.
Rudaz)Research&Services216'000FondsIndustrie(J.
L.
Wolfender,M.
Cuendet,Ph.
ChristenResearch&Services66'183FondsIndustrie(J.
L.
Wolfender,M.
Cuendet,Ph.
Christen)Research&Services90'7126.
PATENTSNo1254209:Extraitsdesarmentsdevigne,compositionslescontenantetleurutilisationcommeagentantipathogènepourlesplantes(2012),Gindro,K.
,Maxant,F.
-X.
,Schnee,S.
,Dubuis,P.
H.
,Wolfender,J.
-L.
,FerreiraQueiroz,E.
F.
andGodefroy,P.
ANNUALREPORT201257CLINICALPHARMACEUTICALASSOCIATEPROFESSORChantalCSAJKASCIENTIFICCOLLABORATORSMoniaGUIDIAlicePANCHAUDPH.
DSTUDENTSEtienneWEISSKOPFElyesDAHMANEVerenaGOTTAGENERALDESCRIPTIONOFTHELABORATORYORGROUPClinicalPharmacyisanemergingdisciplinewhosemainaimsaretodevelopdrugresearchandeducationorientedtowardspatientcare.
Theactivitiesofthegroupisdividedintotwomainaspectsthatcomprises(i)drugindividualizationtroughpopulationpharmacokinetic,pharmacodynamicandpharmacogeneticmodellingthatallowscharacterisationofthedose-concentration-responserelationshipsofdrugsand(ii)drugoptimizationinvulnerablepopulations,suchaspaediatrics,geriatricsorcriticallyillpatients.
Thepopulationapproachisaverysuitablemethodtocapturethecombinedeffectsofmultipledemographic,environmental,orgeneticfactorsthatcaninfluencedruglevelsandpotentiallymodulatedrugresponseortoxicity.
Thegroup'interestsarealsofocusedondoseadjustmentstrategiesfordrugsfollowedbytherapeuticdrugmonitoring.
Ourgroupisworkinginclosecollaborationwithseveralresearchgroupsandclinicalunitsforspecificresearchprojectsandisparticipatingtolocalnationalandinternationalclinicalstudies.
Severalimportantprojectsintheareaofanti-infective,oncologicandpsychotropictreatmentsareon-going.
Thegroupisalsomandatedbyindustrialcompaniestoconductpopulationpharmacokineticstudiesfordrugsduringtheirclinicaldevelopmentphases.
Ourexpertiseallowsfordruganalysesandsimulations,whichcanprovideamoreglobalunderstandingofthedrugkineticsalongwithintersubjectvariabilityandcovariateeffect,whichisofmajorinterestfortheclinicaldevelopmentofnewcompounds.
ThegroupisalsoinvolvedintothepregraduateteachingofclinicalpharmacyattheMasterlevelandissupervisingmasterthesesanddoctoralthesesinthefieldofclinicalpharmacy.
Since2012,itisalsoteachingandsupervisingbachelorthesisatthe"HauteEcoleSantéVaud"formid-wifes.
SPECIFICRESEARCHFIELDSAnti-HIV/HCVdrugs.
ThegrouphasbeeninvolvedinthefieldonHIVtherapyforseveralyears.
ThisresearchareahasbeenextendedtothestudyofHCVdrugsfrequentlyusedincombinationwithantiretroviraldrugs.
ThisyearhasbeenfocusedontheelaborationofprotocolsandresearchplansaimingatstudyingthepharmacokineticsofrecentHCVanti-proteasesdrugsinthetargetpopulationofco-infectedpatientsandforHIV/HCVinteractionstudies.
SupportfromtheFNShasbeengrantedforthisprojectin2012.
Optimisationofthetherapeuticdrugmonitoring(TDM)byprovidingbetterinterpretationtoolsisanotherimportantfocusofthegroupincollaborationwiththeCHUVandtheEPFL(IsyPemProjectpartofthenano-teraproject).
ThisincludesthedevelopmentofnewmethodsforthedescriptionofthekineticprofileofHIVandotherdrugsbasedonmeta-analysisapproachesandtheelaborationofaTDMsoftwarethatwillbemadeaccessibletoclinicians.
Oncologictreatments.
Severalstudiesarecontinuinginthefieldoforaloncologictreatments.
Thepharmacokineticsandmetaboliteprofilingoftamoxifeninpatientstreatedforbreast-cancer,inrelationtogeneticpolymorphismandothersourcesofvariabilityiscurrentlyunderinvestigation.
Researchsupportbyaprivatefoundatationhasbeengrantedforthisstudy(Tamoxifenmetabolismandtheimpactoftamoxifendoseontheleveloftheactivemetabolitesinendocrinesensitivebreastcancerpatients.
(K.
Zaman,mainapplicant,LA.
Décosterd,C.
Csajka,CB.
Eap,T.
Buclin,co-applicants).
Thestudyofimatinibinpatientswithchronicmyeloidleukaemiaorgastro-intestinalstromaltumourhasprovidedconfirmatoryresultsregardingtheconcentration-effectrelationshipsofthisdrug.
ThefirstrandomizedstudyevaluatingtheutilityoftheTDMofimatinibhasbeenfulfilled.
Althoughinsufficientpatientscouldbeenrolledtoprovideconclusiveresults,thisstudycoulddemonstratesomeutilityoftheTDMapproachincaseoftoxicityortreatmentfailure.
AfirstprototypetoolfordosageindividualisationbasedonpopulationpharmacokineticanalysesisavailablethroughcollaborationwiththeEPFL(IsyPem,nano-teraproject).
58ANNUALREPORT2012Psychotropicdrugs.
AmulticentrestudyinvolvingtwoSwissandtwoFrenchmaternitieshasstartedin2012,whoseobjectivesaretoassesstheexposureofbreastfedinfantstoantidepressantdrugsandtoevaluatetheimpactofthistreatementontheirneuro-comportmentaldevelopment.
Inaddition,severalcollaborativeprojectsonthepharmacokineticsofpro-cognitiveandpsychotropicdrugshavebeenperformedincollaborationwiththeCHUV.
Anti-infectiousagents:Thepharmacokinetic,pharmacodynamicandpharmacogeneticsanalysesofsomeantibiotics,anti-malariaandantifungaldrugshaveallowedabettercomprehensionoftheirpharmacokineticsandsourcesofvariabilityandhavecontributedtooptimisationoftheirtherapeuticmanagement.
SPECIFICPROJECTSINITIATEDANDRECOGNITIONSAnewresearchprojectonnewlymarketedanti-hepatitisCdrugsthatarefrequentlyassociatedtoantiretroviraldrugsandsusceptibletomanydrug-druginteractionshasbeeninitiated.
AgranthasbeengrantedtotheSNF(ClinicalpharmacologyandpharmacogeneticsinthecomplexcareofHIVandHIV/HCVco-infectedindividuals.
LA.
Décosterd,mainapplicant,A.
Rauch,C.
Csajka,T.
Buclin,A.
Telenti,co-applicants).
Thegroupisinchargeofupdatingthebook"Médicaments,GrossesseetAllaitement.
J-F.
Delaloyeetal.
EditorsMédecine&Hygiène.
Thesettingupofanewcertificateofadvancesstudiesinclinicalpharmacy(CAS)withinthecontinuouseducationprogramattheUNIGEisinprogress.
11.
.
((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE4499))PUBLICATIONS1.
1SCIENTIFICPUBLICATIONS(WITHIMPACTFACTOR)81.
2SSCCIIEENNTTIIFFIICCPPUUBBLLIICCAATTIIOONNSS((WWIITTHHOOUUTTIIMMPPAACCTTFFAACCTTOORR))21.
3BBOOOOKKCCHHAAPPTTEERR222.
.
((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122PPAAGGEE5500))POSTERSPRESENTATIONS2.
1POSTERSPRESENTATIONS833.
.
((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122PPAAGGEE5511))ORALPRESENTATIONS3.
1CONTINUINGEDUCATION&OPENTOTHEPUBLICLECTURES84.
PUBLICRESEARCHFUNDS(FNSR,NIH,CTI)FNRSFN324730141234_1.
ClinicalPharmacologyandPharmacogeneticsIntheComplexCareofHIVandHIV/HCVco-infectedIndividuals.
Dr.
L.
Decosterd,DrA.
Rauch,Dr.
C.
Csajka,Prof.
T.
Buclin,Prof.
A.
Telenti(co-applicant:472'000.
-;(1post-doctoralposition50%for3years)FOUNDATIONROBERTOETGIANNAGONNELLATamoxifenmetabolismandtheimpactoftamoxifendoseontheleveloftheactivemetabolitesinendocrinesensitivebreastcancerpatients.
DrK.
Zaman,Dr.
C.
Csajka,DrLADecosterd,DrT.
Buclin,ProfS.
Leyvraz(co-applicant;CHF116'490.
-).
5.
RESEARCHFUNDS(INDUSTRYANDASSIMILATED)CodeServiceDevelopmentResearchAmountfor2012(CHF)IndustryMandateforapharmacokineticstudy16'000.
-CHFANNUALREPORT201259COMMUNITYPHARMACYPPRROOFFEESSSSOORRAASSSSOOCCIIAATTEEOlivierBUGNONPPHHAARRMMAACCIISSTTSS,,RREESSEEAARRCCHHAASSSSOOCCIIAATTEESSMariePauleSCHNEIDERVOIROLSavianaDIGIOVANNIJean-FranoisLOCCASophieDUPASQUIERPPHHAARRMMAACCIISSTTSS,,PPHH.
.
DDSSTTUUDDEENNTTSSIsabelleANGUISHAurélieGERTSCHJulienMARQUISStéphanieTROXLERJenniferCELIOMinette-JolleZEUKENG-ZEBAZEPPHHAARRMMAACCIISSTTSS,,CCOOMMMMUUNNIITTYYPPHHAARRMMAACCYYDeniseHUGENTOBLERHAMPAJérmeBERGERMarie-JoséBARBALATAlineBOURDINJenniferCELIOJeremyDeMOOIJNollieGENREDeniseJOSSLaureNICOLETPaulinePAPINVanessaPAVONCLEMENTElodieRESENTERRAMurielSCHUETZStéphanieTROXLERSandrineVONGRUENIGENAADDMMIINNIISSTTRRAATTIIVVEEAANNDDPPHHAARRMMAACCYYTTEECCHHNNIICCIIAANNSSChristelleBADINOVéroniqueGROGNUZRaphalNAOUXStéphanieBURNATTORRINathalieISCHERMatthiasREYMERMIERLaurianneCURTETNolleKAECHMirjamRUFENACHTSoniaDESSELBERGERStefaniaMAGNOLjiljanaSCHLAEFLI,SéverineGORGERATNadiaMARTELGGEENNEERRAALLDDEESSCCRRIIPPTTIIOONNOOFFTTHHEEUUNNIITTThefactofprescribing,recommendingorswallowingadrugseemsbanalandyettherearemanytraps:sideeffects,insufficientefficacy,toohighcosts,non-adherence,waste,lackofmotivation,alteredqualityoflife,etc.
Thesetopics,aswellastheevolutionofpharmaceuticalpracticesareconsideredasprioritiesofactionforacademicandclinicactivitiesofthePharmacyofthePMU(PolicliniqueMédicaleUniversitaire),auniqueplaceinSwitzerland,whichcombinescommunitypharmacypracticewithcollaborativecommunitypharmacyresearchanduniversitaryteaching.
OlivierBugnon,chiefpharmacist,isontheotherhandanassociatedprofessortotheSchoolofpharmaceuticalsciences(UniversityofGeneva,UniversityofLausanne);likethis,heparticipatesinthedevelopmentofcommunitypharmacypractice,apharmaceuticalsciencewhichrespectsthehealthcareprioritiesandthecentralroleofthepatient.
HismainteachingresponsibilityistheorganizationofthesecondyearoftheMasterinPharmacy(yearofassistantship).
HesupervisestheexaminationsoftheMasterandrepresentstheSchoolofpharmaceuticalsciencesintheFederalCommitteefortheorganizationandevaluationofthefederalexaminationforpharmacists.
Hisresearchactivities(5PhDstudentsinpharmaceuticalsciencesin2012)explorewaysofcollaborationbetweenphysicians,pharmacistsandotherprofessionalstoimprovetheresponsibleuseofmedicines(effectiveness,safety,efficiency).
Internationally,thegroupofcommunitypharmacyisrepresentedespeciallywithintheInternationalPharmaceuticalFederation(FIP),theEuropeanSocietyofClinicalPharmacy(ESCP),thePharmaceuticalCareNetworksinEurope(PCNE)andtheEuropeanSocietyforPatientAdherence,COMplianceandPersistence(ESPACOMP).
SSPPEECCIIFFIICCRREESSEEAARRCCHHFFIIEELLDDSSTheresearchoftheGroupofCommunityPharmacyPracticecoversthethreefollowingareas:60ANNUALREPORT20121.
INTEGRATEDCARETheglobaltrendforhealthsystemsiscoordination,networkingandcontinuityofcare.
PharmacistsareattheinterfaceofthetreatmentsprescribedbythephysiciansandtheOTCtreatments.
Theevolutionoftheirroleturnstowardscollaborativepharmacypractice,aimingatthequalityofthecareandcontrolofthecosts.
In2012,theareaintegratedcareofthepharmacyofthePMUworkedonthefollowingtopicsandprojects:Qualitycirclesphysicians-pharmacists-nursesinnursinghomes(cantonalprojectsinFribourgandVaud)Riskevaluationandmitigationstrategies–REMSandpatientprograms(e.
g.
Patientwithcardiovascularrisk;patientswithoralanticancermedications)AnimationofthenetworkofthepharmacistsspecializedinAddictionMedicineintheFrench-speakingpartofSwitzerland-COROPHA(projectsupportedbytheFOPH)Theresearchonintegratedcareiscloselylinkedtothetwootherareastherapeuticadherence(e.
g.
oncology)andsafetyandcosteffectivenessofdrugs(e.
g.
ingeriatrics).
Thisresearchinvolvestraversescientificcollaborationsbetweenpharmaceutical,medical,humanandeconomicsciences.
2.
MEDICATIONADHERENCEThedailyandprolongedtakingofmedicineisdifficultforchronicpatients,especiallyincaseofsideeffects,complextreatments,lackofmotivation,incomprehensionorrefusalofthetreatment.
Tosometimesforgettotakeone'smedicineisneverthelessanormalhumanbehavior.
Themedicationadherencedefinesitselfasanactiveprocessinwhichthepatientworkstomaintainhishealthincollaborationwiththemedicalteam.
TheresearchersofthePharmacyofthePMU,incollaborationwithvariousphysiciansandnurses,areinterestedinthescientificdevelopmentandevaluationofaroutineadherenceconsultationindomainslikeforexamplehighbloodpressure,VIHinfections,oralanticancermedications,transplantations.
Theadherenceconsultationisconcretizedby:Motivational,semi-structuredinterviews,leadbyapharmacist;Themeasureofmedicationadherencethroughanelectronicmedicationboxandit'srelationwiththeeffectsofthetherapy;Thesharingofdatacollectedinpharmacies(persistence,qualityofexecution,sideeffects,perceptionsofpatientsandtheirrelatives)withthemedicalandcaretakingteamTheresearchontheadherencealsocontributestothegoalsoftheareaintegratedcare(e.
g.
inoncology).
3.
SAFETYANDCOSTEFFECTIVENESSOFDRUGSDrugsrepresenttheoptionmostfrequentlyusedbythephysicians.
Theprescriptionformalizesthetherapeuticplanwiththeconcordanceofthepatient;itrepresentsanessentialcommunicationtoolforthecollaborationwiththepharmacist.
Drugrelatedproblemsexperiencedbythepatientsandmedicationerrorsaretoofrequent.
Theyareusuallyasignofsystemfailure,acostfactorandbreaksoftheseamlesscare:manygoodreasonstostudyscientificallytheprovidedserviceslikelytocontroldrugriskmanagementaswellastoimprovesafety,effectivenessandefficiencyofthemedicines.
Amedicationreviewisaglobalandstructuredanalyzeofthewholepharmaceuticalrecordofchronicpatients.
Thisprovidedservicecan,inadditiontothemedicationrecord,baseitselfoninterviewswithpatientsaswellasonsomeclinicaldata(laboratoryvalues,therapeuticgoals,pasthistories,.
.
.
)suppliedbythephysicians.
Thosecannowactbytakingintoaccountpropositionsformulatedbythepharmacists.
Thisresearchareaisnaturallycloselylinkedwiththetwootherareastherapeuticadherenceandintegratedcare.
OOUUTTSSTTAANNDDIINNGGPPUUBBLLIICCAATTIIOONNSSG.
GRAS,M.
-P.
SCHNEIDER,M.
CAVASSINI,F.
LUCHT,M.
LOILIER,R.
VERDON,L.
BERNARD,J.
-J.
PARIENTIPatternsofAdherencetoRaltegravir-BasedRegimensandtheRiskofVirologicalFailureAmongHIV-InfectedPatients:TheRALTECAPSCohortStudy.
JAIDS2012,61:265-269O.
BUGNON,D.
HUGENTOBLER-HAMPA,J.
BERGER,M-P.
SCHNEIDERNewRolesforCommunityPharmacistsinModernHealthCareSystems:AChallengeforPharmacyEducationandResearch.
CHIMIA(2012February);66:No.
5,304-307I.
KRUMMENACHER,M.
CAVASSINI,O.
BUGNON,M-P.
SCHNEIDERCharacteristicsofHIVpatientsreferredtoamedicationadherenceprograminSwitzerland.
IntJClinPharm2012,34:426-431SSPPEECCIIFFIICCPPRROOJJEECCTTSSIINNIITTIIAATTEEDDAANNDDRREECCOOGGNNIITTIIOONNSSSince1stAugust2012,consolidationofacademicsupervisionoftheCommunityPharmacyGroupoftheSchoolofpharmaceuticalsciences(UniversityofGeneva,UniversityofLausanne)bytheappointmentofDrMariePauleSchneideras"collaboratricescientifique2".
In2012,theCommunityPharmacyofPMUgoessuccessfullythroughthefollowingcertification/accreditationsteps:1.
RenewalofthecertificationISO9001:2008/Healthmark–2.
FirstintermediateQMS-PharmacyAudit(pseudo-patientwithaRxprescription)inaccordancewiththeprofessionalstandardISASQMS-Pharma2010.
ANNUALREPORT201261O.
BUGNON,representativeoftheSchoolofpharmaceuticalsciences(UniversityofGeneva,UniversityofLausanne)intheFederalCommitteeinchargeoftheorganizationoftheannualfederalexaminPharmacy,asrequestedbythefederallawonthemedicalprofessions(LPMed).
O.
BUGNON,presidentofthenationalworkinggroupPAP("PlatformAusbildungPharmazie")ofpharmaSuisse(Swisssocietyofpharmacists)aimingatthecoordinationinpre-graduateeducationbetweentheuniversities(Basel,Bern,Fribourg,Geneva,Neuchtel,Zürich),theSwissassociationofpharmacystudents(asep),theFederalOfficeofPublicHealth(FOPH)andtheprofessionalassociationsandotherinterestgroups(pharmaSuisse,Swisssocietyofhospitalpharmacists,Swisssocietyofindustrypharmacists);meetingsinBern(27.
06.
2012and07.
11.
2012).
M.
P.
SCHNEIDER,mandatedforSwitzerlandbytheABCproject(AscertainingBarrierstoCompliance:policiesforsafe,effectiveandcost-effectiveuseofmedicinesinEurope),fundedbytheEuropeanCommissionSeventhFrameworkprogramme(FP7ThemeHealth);principalinvestigator:DrW.
Clyne,SchoolofPharmacy,KeeleUniversity.
Project:Managementofpatientmedicationadherence:asurveyofdoctors,pharmacistsandnursesin16Europeancountries.
SurveyconductedfromJune2011toMay2012.
O.
BUGNON,mandatedforthedevelopment,teachingandevaluationofthemodule"RiskManagement"forthenewExecutiveMBAinHealthcareSpecialisationlaunchedbytheInstitutd'économieetmanagementdelasanté(IEMS)(UniversityofLausanne):Riskmanagementstrategiesforoptimizingtheperformanceofhealthcaresystem,providersandindustries.
,Lausanne,12-13.
10.
2012.
A.
Niquille,MPSchneider,D.
NanchenandJ.
Cornuz,inchargeofthedevelopmentandimplementationoftheclinicalresearchqualityprojectofthePolicliniqueMédicaleUniversitaire(PMU)andtheUniversityDepartmentofCommunityMedicineandHealth(DUMSC),UniversityofLausanne.
O.
BUGNON,N.
MARTEL,S.
DESSELBERGER,respondedpositivelytotherequesttovisitthe"PharmaciedelaPMU"3daysbyadelegationoftheJapaneseAssociationofPharmacyinterestedbythefollowingtopics:qualiycirclesphysicians,pharmacists,nursesinprimarycareandinnursinghomes;collaborativeprogramspromotingthemedicationadherence,innovativetrendsincommunitypharmacypractice.
EstablishmentofanagreementofcollaborationbetweenPMU,O.
Bugnonandthestart-upSISPhaSA(www.
sispha.
com),createdtofacilitatetheimplementationincommunitypharmaciesofcollaborativepharmaceuticalservicescurrentlyremuneratedbytheinsurers(RBP)andmoreparticularythecoachingofchronicpatients,medicationadherenceandpostmarketingriskevaluationandmitigationprograms(PhaseIV).
CCOONNGGRREESSSSEESSOORRGGAANNIISSEEDDO.
BUGNON,scientificexpertfortheSymposiaPharmacyonTop,organizedbyMEPHAPharmaSAwiththesupportofSISPhaSA,onthetopicofleadershipandchangestrategies:Retrouverunnouveausouffle:l'exempledeceuxquiontréussiinMontreux(26.
4.
2012)andinLausanne-Bussigny(27.
4.
2012)PremierspasenEntretiensmotivationnels,inLugano(3.
5.
2012).
M.
J.
ZEUKENG,memberofthesymposiumcommitteeandchairmanofthePhDDay2012oftheSchoolofpharmaceuticalsciences(UniversityofGenevaandUniversityofLausanne),FondationBrocher,Hermance(Geneva),15.
06.
2012.
M.
P.
SCHNEIDER,memberofthescientificcommittee,ofthebestpostercommitteeandworkshopleaderofthe15thAnnualmeetingofESPACOMP(EuropeanSocietyforPatientAdherence,COMplianceandPersistence,Ghent(Belgium),26-27.
10.
2012.
O.
BUGNON,memberofthesymposiumcommitteeandchairmanforthescientificsymposiumorganizedattheoccasionofthePolicliniqueMédicaleUniversitaire's(PMU)125thanniversary:LittératieetWeb2.
0:chancesetdéfispourlasanté,Lausanne,14.
11.
2012.
O.
BUGNON,memberoftheconferencecommitteeandworkshopleaderofthe8thPharmaceuticalCareNetworkinEurope(PCNE)WorkingConference[Collaborativepharmaceuticalcareinresearchandpractice]plannedfor6-8February2013inBerlin[www.
pcne.
org].
11.
.
PPUUBBLLIICCAATTIIOONNSSDDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE5522))(1.
1SCIENTIFICPUBLICATIONS(WITHIMPACTFACTOR)31.
2SCIENTIFICPUBLICATIONS(WITHOUTIMPACTFACTOR)151.
3PUBLICATIONSEXTRAMUROS21.
4BOOKSORBOOKSCHAPTERS822.
.
PPOOSSTTEERRSSPPRREESSEENNTTAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE5555))2.
1POSTERSPRESENTATIONS662ANNUALREPORT201233.
.
OORRAALLPPRREESSEENNTTAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE5555))3.
1CONGRESS&SYMPOSIA253.
2CONTINUINGEDUCATION&OPENTOTHEPUBLICLECTURES3444.
.
TTHHEESSIISSPPRREESSEENNTTEEDDM.
SCHTZViolencesconjugalesenverslesfemmes:quepeutfairelepharmaciend'officinePharmaciecommunautaire,Sectiondessciencespharmaceutiques,UniversitédeGenèveetUniversitédeLausanne.
UnitédeMédecinedesviolences,DUMSC,CHUV,UniversitédeLausanneSupervisor:DrMarie-ClaudeHofner55.
.
PPUUBBLLIICCRREESSEEAARRCCHHFFUUNNDDSS((FFNNSSRR,,NNIIHH,,CCTTII))FFEEDDEERRAALLOOFFFFIICCEEOOFFPPUUBBLLIICCHHEEAALLTTHH((FFOOPPHH))Réseaumédecins-pharmaciensdansledomainedel'addiction–Formationetintégrationdupharmaciendansleréseauinterdisciplinairedepréventionetdepriseenchargedel'addiction.
"Consolidationdesacquisd'étudesprécédentesetdéveloppementdesstandardsdequalitépourlapratiqueofficinales'appliquantàlapriseenchargedesproblématiquesd'addiction(drogue,alcoolettabac)"-(ContratNo.
09.
004964/204.
0001/-650)[Integrationofpharmacistsintheinterdisciplinarynetworkforthemanagementofaddictions]Mainapplicant:O.
BugnonCo-applicant:S.
duPasquierTotalallocation:CHF79'000.
-Allocation2012:CHF7'000Duration:4yearsStartingdate:2009Elaborationdel'ExamenfédéralenPharmacie:participationdesexpertsdelaSectiondessciencespharmaceutiques(UniversitédeGenève,UniversitédeLausanne)-(ContratNo.
12.
002085/704.
0001/-527)-[ElaborationoftheFederalExamforPharmacy2012]Mainapplicant:O.
BugnonAllocation2012:CHF187'348Duration:1yearCCAANNTTOONNAALLOOFFFFIICCEEOOFFPPUUBBLLIICCHHEEAALLTTHH––VVAAUUDDEncadrementscientifiqued'unprogrammed'assistancepharmaceutiquedesétablissementsmédico-sociauxpourpersonnesgées(EMS)vaudois[Development,implementationandevaluationofanewcantonalcollaborativecaremanagementprogrammeinnursinghomes(physicians-nurses-pharmacistsqualitycircles]Mainapplicant:O.
BugnonTotalallocation:CHF180'000.
-Allocation2012:CHF30'000Duration:6yearsStartingdate:200755.
.
RREESSEEAARRCCHHFFUUNNDDSS((IINNDDUUSSTTRRYYAANNDDAASSSSIIMMIILLAATTEEDD))CodeMandatsdeprestationsetderechercheMontantspour2012(CHF)ABEC3Rechercheetdéveloppement6'500CP3Formation7'900SAN6Rechercheetdéveloppement20'000SM10Rechercheetdéveloppement10'000SOVAPHRechercheetdéveloppement10'000NOV8Rechercheetdéveloppement48'160PFI6Rechercheetdéveloppement17'000PHA11Formation7'000PFI6Rechercheetdéveloppement17'000TAS11Rechercheetdéveloppement30'000173'560*LesfondsderechercheduProf.
O.
BugnonsontofficiellementcontrlésparledépartementdesFinances,PMU,Lausanne.
ANNUALREPORT201263HOSPITALPHARMACYPPRROOFFEESSSSOORRSSAASSSSOOCCIIAATTEESSProfPascalBONNABRYHUGPharmacyProfAndréPANNATIERCHUVPharmacyPPHH.
.
DDSSTTUUDDEENNTTSSHHUUGGMarcoANASTASIDelphineCARLIOliviaFRANCOISAnne-LaureBLANCMapiFLEURYLaure-ZoéKAESTLILaurentCARREZPPHH.
.
DDSSTTUUDDEENNTTSSCCHHUUVVJean-ChristopheDEVAUDDavidPALMEROHanitraRAVELOJAONAAnneHENRYCatherinePLUESS-SUARDGGEENNEERRAALLDDEESSCCRRIIPPTTIIOONNOOFFTTHHEEUUNNIITTThetwoprofessorsofthegroupareheadofthehospitalpharmaciesatCHUV(Lausanne)andHUG(Geneva)and,inthiscontext,developresearchandeducationactivitiesinhospitalandclinicalpharmacy.
Theundergraduateeducationisespeciallyfocusingonthefollowingtopics:Drugselection,drugflow,andpharmacoeconomicsProductionandqualitycontrolofdrugsatthehospitalMedicaldevicesandmateriovigilanceRiskmanagementInformationondrugs,infovigilanceClinicalpharmacy,especially:oPharmacyinclinicalnutritionoPharmacyinintensivecareunitsoPharmacyinpaediatricsoPharmacyinsurgicalunitsApost-graduateeducation(MAS)inhospitalpharmacyisalsoproposedonthetwositessince1999.
Thisthreeyearprogrammeisacompletespecialisationinhospitalpharmacy,associatingtheoreticalandpracticalteachings,aswellasaoneyearresearchproject.
BothhospitalsalsoproposepositionsofPhDstudentsinpharmaceuticalsciences,eitherforpharmacistshavingfinishedtheirMAS,orindirectaccess.
Formoreinformation:CHUVpharmacy:www.
chuv.
ch/phaHUGpharmacy:http://pharmacie.
hug-ge.
chSSPPEECCIIFFIICCRREESSEEAARRCCHHFFIIEELLDDSS1)SafetyofdruguseprocessinhospitalsProactiveriskanalysisinhospitalprocesses,applicationoftheFMECAmethod.
Impactofinformationtechnologiesonpatientsafetyatprescription,dispensingandadministrationlevels.
Impactofhumanfactorsonerrorratesatdifferentstepsofthemedicationuseprocess.
64ANNUALREPORT20122)OptimisationofdrugadministrationDevelopmentofready-to-useformulationsadaptedtohospitalspecificities,andvalidationofasepticproductionprocesses.
Evaluationofthequalityofmedicaldevicesinvolvedindrugsadministration.
Evaluationandimprovementofspecificadministrationtechniques(i.
e.
enteralfeedingtubes,nebulisation,intrathecal).
3)PharmacoeconomicanalysesofdruguseinthehospitalEvaluationofcost-benefitratiosoftreatments.
Evaluationofspill-overeffectbetweenthehospitalandtheambulatorycaresettings.
OOUUTTSSTTAANNDDIINNGGPPUUBBLLIICCAATTIIOONNSSHHUUGGS.
NUSSBAUMER,L.
GEISER,F.
SADEGHIPOUR,D.
HOCHSTRASSER,P.
BONNABRY,J.
-L.
VEUTHEY,S.
FLEURY-SOUVERAIN.
WipesamplingprocedurecoupledtoLC-MS/MSanalysisforthesimultaneousdeterminationof10cytotoxicdrugsondifferentsurfaces.
AnalyticalBioanalyticalChemistry,402,2499-509,2012.
OOUUTTSSTTAANNDDIINNGGPPUUBBLLIICCAATTIIOONNSSCCHHUUVVJ.
-C.
DEVAUD,M.
M.
BERGER,A.
PANNATIER,P.
MARQUES-VIDAL,L.
TAPPY,N.
RODONDI,R.
CHIOLERO,P.
VOIROL.
Hypertriglyceridemia:apotentialsideeffectofpropofolsedationincriticalillness.
IntensiveCareMed,DOI10.
1007/s00134-012-2688-8;38:1990–1998,2012.
C.
PLSS-SUARD,A.
PANNATIER,C.
RUFFIEUX,G.
KRONENBERG,K.
MHLEMANN,G.
ZANETTI.
Changesintheuseofbroad-spectrumantibioticsaftercefepimeshortage:atimeseriesanalysis.
Antimicrob.
AgentsChemother.
,56(2),989-994,2012.
11.
.
PPUUBBLLIICCAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE6611))1.
1ASCIENTIFICPUBLICATIONS(WITHIMPACTFACTOR)HUG51.
1BSCIENTIFICPUBLICATIONS(WITHIMPACTFACTOR)CHUV91.
2ASCIENTIFICPUBLICATIONS(WITHOUTIMPACTFACTOR)HUG91.
2BSCIENTIFICPUBLICATIONS(WITHOUTIMPACTFACTOR)CHUV41.
3ABOOKSORBOOKSCHAPTERSHUG11.
3BBOOKSORBOOKSCHAPTERSCHUV122.
.
PPOOSSTTEERRSSPPRREESSEENNTTAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE6644))2.
1APOSTERSPRESENTATIONSHUG292.
1BPOSTERSPRESENTATIONSCHUV1633.
.
OORRAALLPPRREESSEENNTTAATTIIOONNSS((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE6666))3.
1ACONGRESSES&SYMPOSIAHUG113.
1BCONGRESSES&SYMPOSIACHUV83.
2ACONTINUINGEDUCATION&OPENTOTHEPUBLICLECTURESHUG193.
2BCONTINUINGEDUCATION&OPENTOTHEPUBLICLECTURESCHUV3044.
.
TTHHEESSIISSPPRREESSEENNTTEEDD44.
.
11.
.
IINNTTRRAA--MMUURROOSSTTHHEESSIISS(HUG)LilianeGSCHWINDAnticoagulationparantivitaminesK:analysedesinteractionsmédicamenteusesetdespolymorphismesgénétiquesàl'originedelavariabilitédelaréponseetdesrisquesliésàl'acénocoumarolUniversityofGeneva–2012–Supervisor:Prof.
J.
DESMEULESCo-Supervisor:Prof.
P.
BONNABRY44.
.
22.
.
IINNTTRRAA--MMUURROOSSTTHHEESSIISS(CHUV)CatherinePLSS-SUARDSuividelaconsommationdesantibiotiquespourlapromotiondeleurbonusageetlamatrisedelaresistancebactérienneenmilieuhospitalier:miseenplaceetexemplesd'utilisation.
UniversityofGeneva–2012–Supervisor:Prof.
A.
PANNATIERCo-supervisor:ProfG.
ZanettiANNUALREPORT201265DOCTORALPROGRAMCCOOUURRSSEESSAANNDDSSYYMMPPOOSSIIAATable1ListofcoursesorganizedwithinthePhDPrograminPharmaceuticalSciences2012andnumberofparticipantsNameofcourse2012#courseResponsibleProfessor#ofhourscredits#StudentsSpectrométrieenmasse1506BCRG.
HopfgartnerE.
Varesio06+mastersSpectrométriedemasse(exercices)1506BEXG.
HofgartnerS.
MichaletE.
Varesio284inclus1506BCR6+mastersAnalyticaltoolscharacterizingprotein-ligandinteractions19H002R.
Perozzo6110Assistancepharmaceutiqueetpharmacieclinique19H003P.
Bonnabry18313,total23AssuranceQualité(AQ):Rle,activitésetexigencesauseind'uneindustriepharmaceutique19H004E.
AllémannS.
CampionePh.
Meuwly162.
515Caractérisationstructuraledeproduitsnaturels19H006J.
-L.
WolfenderE.
Ferreira-Queirros1228Dispositifsmédicauxetmatériovigilance19H008A.
Pannatier1837,total33Formulationofproteinbiopharma-ceuticalanddrugdelivery19H013T.
Arvinte203.
56,total36Initiationàl'électrophorèsecapillaire19H016S.
Rudaz1836Lesbrevetsdanslarecherche-sourced'informationetmoteurdel'innovation19H018L.
ScapozzaJ.
DeWerraP.
DucorD.
KrausL.
MiévilleR.
TschudinP.
Weibel223.
510,total11Essentialsinmolecularandappliedpharmacology19H019U.
Rüegg142.
59Physiopathologieoculaireetmoyensthérapeutiques:diabèteetdèmemaculaire19H021C.
Tabatabay1223Structuralbioinformaticsandmolecularmodeling19H028L.
ScapozzaW.
BissonH.
Scheib30523Techniquesdepréparationd'échantillons,casdematricessolides19H029Ph.
Christen61ANNULEmanqueinscriptionsToxicologieAnalytiqueForensique19H031Ch.
Staub81.
51166ANNUALREPORT2012Nameofcourse2012#courseResponsibleProfessor#ofhourscredits#StudentsUseoffluorescencespectroscopyinthestudyofdrugs,proteinandmembrane19H032T.
Arvinte1225,total20Validationdeméthodesanalytiques19H034S.
Rudaz18312Productionstérile:MéthodesetEnvironnement19H044F.
Sadeghipour1937TherapeuticDrugMonitoringanditsApplicationinDiagnosticsandClinicalResearch19H045L.
Decosterd618Initiationauxméthodesd'analysemultivariéesensciencespharmaceutiques19H046S.
RudazJ.
Boccard12215Introductiontoplantmetabolomics19H047J.
-L.
Wolfender162.
511PhDGE21PhDNEInnovationcollaborativeouOpeninnovationausecoursdelarecherchetdudéveloppementpharmaceutique19H049L.
ScapozzaE.
LePouls183ANNULEàlademandedeE.
LePouls24.
9.
12BiochipsforhealthresearchGRENCR02J.
Breton2442,total32visitransmissBiotechnologieMoléculaireGRENCR03M.
Seve244ANNULETOTAL24178Ph133others*)ThecoursedescriptioncanbefoundunderthewebpageoftheSchoolofPharmaceuticalSciences,EPGLhttp://epgl.
unige.
ch/pharm/fr/Table2ListofsymposiaorganizedwithinthePhDPrograminPharmaceuticalSciences2012andnumberofparticipants*.
Nameofcourse2012-2013#courseResponsibleProfessor#ofhourscredits#StudentsSymposiumPharmapeptides19H001G.
Borchard6110PhD35others-PhDDay19H020L.
Scapozza61or264PhD7post-doc+prof.
+1speakerConférencessursujetsspécialisésG.
Hopfgartner1,5pour5conf.
Table3Nameofcourse2012-2013#courseResponsibleProfessor#ofhourscredits#StudentsSéminaireextra-murosZermatt19H024M.
CuendetJLWolfender1or235PhDtotal48Table4ListofnetworkingactivitiesorganizedwithinthePhDPrograminPharmaceuticalSciences2012andnumberofparticipants.
Nameofcourse2012-2013#courseResponsibleProfessor#ofhourscredits#StudentsRencontreavecl'Industrie19H050L.
Scapozza61ANNULEàlademandedeNovartisCareerday19H007L.
Scapozza6146PhD,1stagiaire,1post-doc+1prof.
***)scheduledbeginningof2012ANNUALREPORT201267CCOOMMMMEENNTTSSTheprogramin2012consistedof23coursesThetotalofhoursgivenwithinthe2012PhDprogramwas451(withoutcountingthe"conferencessursujetsspecializes).
Twotypesofcourseswereproposed,namelyweekly(Hebdo)andbloc(Table1).
WithintheframeworkofthePhDprogram,thePhDday,Careerdays,visittoIndustryandtheextra-murosseminarhavealsobeenorganizedwithsuccess(Table2,3and4).
The"SymposiumPharmapeptides"wasnotheldin2011.
Theprogram2012offeredforthefifthyear2coursesviaapartnershipwiththeUFRdePharmaciedeGrenoble(Table1)whichforeseesanexchangeofcoursesbetweenthetwoUniversities.
Oneofthecourseswascancelledandtheotheronewastransmittedbyvisio-conference.
ThePhDprograminpharmaceuticalscienceshasbeenselectedbytheCUSObasedontheresultsachievedduringthe3yearsprojectasoneoftheprojecttobesupportedfurtherinthenextyears.
TheprogramaswellasthebudgetweresubmittedtotheCUSOwhoacceptedthem.
Thebudgetin2012forthefiveactivities(SeminarExtra-Muros,Conférencespécialisées,Cours,SymposiaaswellasNetworkingactivities)wasof79'400.
-CHFcoveredbythefundallocatedbytheCUSO.
Thecostsfor2012foralltheactivitieswere73'160.
01CHF,therevenueswere16'881.
13.
-CHF.
Thismakesacostof56'278.
88CHFfortheCUSObudget.
Thus,wespentlessthanbudgeted.
Thedifferencebetweenthebudgetandthecostsisduetothefactthat:thecourse19H049(Innovationcollaborative.
.
),withabudgetofCHF4'500.
00,wascancelledbytheorganizerasthenumberofparticipantsregisteredidnotfulfillhisexpectations.
Thecostsfortheseminarextra-muroswerelessthanthe36'670.
CHFbudgetedandamountedto29481.
20.
-becauseofhigherrevenues.
Furthermore,thethesuccessfulEnglishcourseshavebeenintegratedintotheCUSOsoftskillofferasof2011.
ItaketheopportunityinthisreporttothanktheCUSOforthepastandfuturefinancialsupportallowingofferinganoutstandingprogramtothePhDstudentsinPharmaceuticalSciences.
FortherenewaloftheCUSOsupport,anexhaustiveevaluationofthePhDprogramhasbeenconductedattheendof2011.
Basedonthepositiveevaluation,CUSOhasdecidedin2012tocontinuetosupportourPhDprogram.
Theschedule,thecontentofthecourses,hoursandcreditsaswellasallindicationsconcerningthePhDprograminPharmaceuticalSciencesarestoredinaMySQLdatabaseandposteddynamicallyonthewebpageofthePhDprogram(http://epgl.
unige.
ch/pharm/fr/[Etudes/programmedoctoral]).
Furthermore,theinformationrelativetotheprogram2012wassentbyE-mailtoallPhDstudentsandsupervisorswellaheadofthebeginningofthecourses.
TheannualinformationmeetingforthePhDstudentswhostartedtheprogramin2012washeldonthe9thofOctober2012inthelectureroom4-457.
Basedontheresultsfromstudents'demandsandregistrationtothedifferentcourses,someofthecourseshavebeenestablishedasannualcourses,othercoursesarescheduledbiannuallyorevery18months.
ThenumberofPhDstudentsenrolledattheEPGLincreasedoverthelastyears,reaching126attheendof2012.
AllofthemaresubmittedtothebylawthatforeseestheparticipationtothePhDprogramandtheacquisitionofatleast30creditsbeforethedefenseofthethesis.
AninterestingnoteisthatmostofthePhDstudentshavemorethan30creditsattheendoftheirPhDindicatingtheiractiveparticipationtothePhDprogram(Table1,Table2,Table3).
Theparticipationwasgoodwithameanvalueof7.
5PhDstudentspercourse.
Ifweconsideralltheparticipantsincludingpostdocsandpre-gradthismean-valueincreasestomorethan10participants,whichistheaimpercourseinrespecttothenumberofparticipant.
InordertoincreasetheexchangeamongPhDstudentsandbetweenPhDstudentsandotherscientists,theseventhPhDdaywasorganizedonthe15thofJune2012bythePhDstudentsofthegroupofHospitalPharmacy.
ThePhDdaywasorganizedinHermanceattheBrocherFoundationwithaprogramincluding1externaland16PhDstudentsspeakers.
64PhDstudents,1speaker,7post-docandprofessorsforatotalof72participantsparticipatedatthisevent.
Thequalityofthetalksanddiscussionaswellastheorganizationwasverygoodfulfillingtheobjectivesofthisday.
ThenextPhDdayisscheduledatthe31stofMay2013andwillbeorganizedbythePhDstudentsofthegroupofpharmaceuticalanalyticalchemistry.
ConsideringthesuccessoftheCareerDayintroducedin2009,itwaserepeatedon.
21stofMay,2012.
46PhDstudents,1stagiaire,1post-docand1professorparticipatedatthedayorganizedbythePhDstudentsofthePharmaceuticalBiochemistry.
8scientistsfromIndustrypresentedtheircompany,workandcareerpossibilities.
Avisittotheindustrywasplannedforsummerorautumn2012butfinallycancelledbyNovartisduetointernalreorganization.
Prof.
LeonardoScapozzaisstilldiscussingfurtherpossibilitiesforvisitstoNovartis,aneventveryappreciatedbythePhDstudents.
ThePhDstudentsattendedregularlytheconferences(conferencesspécialisées)proposedwithinthePhDprogram.
12seminarshavebeengivenbyinternationalresearchersfromacademiaandindustry.
Atotalof289participantsattendedtheselectureseriesincluding75PhDstudents,12pre-graduates,37post-docsand79seniorscientists.
Theyearlyextra-murosmeetingforPh.
D.
studentsinpharmaceuticalscienceswasheldasusualattheParkhotelBeausite(Zermatt,VS).
IttookplacefromSeptember3to7,2012andwasorganizedbyProf.
MurielCuendetandProf.
Jean-LucWolfender.
Thisyearmeetingwasentitled"DrugsfromNature:fromDiscoverytoClinic"andreviewedsomeoftherecentdevelopmentinthefieldofNaturalproductsresearchrelevanttopharmaceuticalsciences.
Fifteennationalandinternationalspeakersactiveinacademiaandindustrypresentedrecenttrendsinvarioustopicsrangingfromaccesstobiodiversity,leadfindingfromnaturalsourcesuptoclinicaldevelopment.
LecturesonthefirstdayweremainlyfocusedonsourcesofnaturalproductsofdifferentoriginwhichincludetraditionalChinesemedicine,venomsandmicroorganism.
Thetwofollowingdayswerefocusedonstrategyforleadfinding,includingtheworkonplants,animalsormicroorganisms.
Variousapproachesonbiologicalscreeningandtheirapplicationwereillustratedeitherbyspeakersfromtheindustryortheacademy.
LocalpeopleinvolvedinWallisforthepromotionofmedicinalplantsalsopresentedtheirnewlyopenedplatformPhytoArk.
ThursdaywasmainlyreservedforclinicalaspectswiththeexampleofthedevelopmentofnaturalproductsbaseddrugfromtheSwisscompanyDebiopharmandonFriday,68ANNUALREPORT2012someprovocativelecturesontheparadigmofdrugdiscoveryweregivenforaninterestingbrainstormingsession.
Severalapproachesforcancerchemopreventionstrategieswerealsobroughtthroughouttheprogram.
Besidethepresentationsfromtheinvitedspeakers,twoeveningsessionswerededicatedtotenshortPh.
D.
studentlecturesandduringoneeveningtheparticipanthadapreviewofanewdocumentaryforARTEonthepotentialofcone'svenomasadrugsource,presentedbyitsauthor,DrRetoStcklinfromAtherisinGeneva.
Themeetingwasattendedby65persons(speakersincluded).
Fifty-twoparticipantscamefromtheEPGLandtheUniversityhospitalsofGenevaandLausanne.
Asusualthemeetingwasevaluatedbytheparticipants.
Mostoftheparticipantswereverysatisfiedbythescientificcontentoftheprogramandappreciatedthepresentationsofthespeakers,aswellasthesetupofthemeeting.
Thisinternational"extra-muros"meetingoffersPhDstudentswithvariousopportunitiesfornetworking.
Summarizing,thekeypointsoftheactivityofthePhDprograminPharmaceuticalSciencesareaprogramcoveringthebroadrangeoffieldsofPharmaceuticalScienceswith23coursesforatotalof451hours,theverygoodparticipationofthePhDstudentstoallfiveactivitiesofthePhDprograminPharmaceuticalSciences.
3855576687991081121241260204060801001201402003200420052006200720082009201020112012NumberofPhDStudentsNumberofPhDStudentsANNUALREPORT201269PROFESSORHONORARYPPRROOFFEESSSSOORRHHOONNOORRAARRYYRobertGURNYRREESSEEAARRCCHHAASSSSOOCCIIAATTEESSAANNDDLLEECCTTUURREERRSSCinziaDEUTSCHSTELLABéatriceKAUFMANNMichaelMLLERPPHH.
.
DD.
.
SSTTUUDDEENNTTSSLutzASMUS1SemaKADERLI(codirection)3MartaRODRIGUEZ4SarraDEVALENCE2MariekeVEURINK3Guarantors(répondants)1Prof.
E.
Allémann2ProfP.
-A.
Carrupt3Prof.
L.
Scapozza4Prof.
J.
-L.
VeutheyAADDMMIINNIISSTTRRAATTIIVVEEAANNDDTTEECCHHNNIICCAALLSSTTAAFFFF*MyrthaCOPIN*SylvieGUINCHARD*BéatriceKAUFMANN*Guarantor(Répondante)AnnickdeMorsierGGEENNEERRAALLPPRREESSEENNTTAATTIIOONNOOFFTTHHEEAACCTTIIVVIITTYYOOFFUUNNIITTSSTheprojectsbelongtothefieldsof(i)drugdeliverytotheeye,(ii)proteinandpeptideformulationandstabilizationand(iii)developmentofnovelpolymericcarriersofsyntheticandnaturaloriginprogressedverywellwiththefilingof3patents.
Novelhybridgelsbasedonnaturalpolymershavebeentestedinhorsesforthetreatmentofarticularpathologiesofthejoint.
SSPPEECCIIFFIICCRREESSEEAARRCCHHFFIIEELLDDSSInthefieldofvascularbloodflowoftheretina,anovelpeptide(BQ123)hasbeentestedsuccessfully.
Locallyappliedintothevitreous,thebioactivesubstanceimprovesthesupplyofoxygenbydilationoftheretinalarteries.
Clinicalindicationsareacuteocclusionofvessels,ischemicconditions,diabeticretinopathy,branchedretialveinocclusion,severestenosisandembolicdiseases.
Theresearchresultswerepresentedatinternationalmeetings.
OOUUTTSSTTAANNDDIINNGGPPUUBBLLIICCAATTIIOONNSSS.
deValence,J.
-C.
Tille,D.
Mugnai,W.
Mrowczynski,R.
Gurny,M.
Mller,B.
H.
WalpothLongtermperformanceofpolycaprolactonevasculargraftsinaratabdominalaortareplacementmodelBiomaterials33,38-47(2012)Doi:10.
1016/j.
biomaterials.
2011.
09.
024PPAARRTTIICCUULLAARRPPRROOJJEECCTTSSIINNIITTIIAATTEEDDAprojectfocusingontheuseofsuperparamagneticironoxideparticles(SPION)fordiagnosisandtherapyofcerebralischemiawasinitiatedwiththeInstituteofMaterialSciences(ICMAB)andtheNeurovascularResearchLaboratoryatValld'HebronHospital(bothinBarcelona,Spain).
1.
((DDEETTAAIILLSSIINNSSCCIIEENNTTIIFFIICCPPRROODDUUCCTTIIOONNSS22001122––PPAAGGEE7711))PUBLICATIONS1.
1SCIENTIFICPUBLICATIONS(WITHIMPACTFACTOR)970ANNUALREPORT20122.
THESISPRESENTED2.
1.
INTRA-MUROSTHESISLutzASMUS(03.
02.
2012)InjectableSustained-ReleaseFormulationsBasedonPolyestersFromSmallMoleculeSolutionstoProteinDeliverytotheEyeUniversityofGeneva–2012–thesisNo.
4403SarradeVALENCE(30.
11.
2012)SyntheticbiodegradablevasculargraftsfortheregenerationofarteriesUniversityofGeneva–2012-thesisN°44963.
PATENTSM.
MLLER,B.
KAUFMANN,R.
GURNY,ProcessfortheesterificationofhyaluronicacidwithhydrophobicorganiccompoundsPCTInt.
Appl.
(2012),WO2012013670A120120202.
M.
MLLER,L.
ASMUS,R.
GURNY,Compositionscomprising2-hydroxyalkanoicacidpolymersandtheiruseindrugdeliverysystemsPCTInt.
Appl.
(2012),WO2012014011A120120202.
R.
GURNY,O.
JORDAN,S.
KADERLIHybridhydrogels,USPat.
Appl.
US61693803S.
KADERLI,O.
JORDANANDR.
GURNY.
HybridhydrogelsUSPATAPPL.
61693803(JULY2012)S.
KADERLI,R.
GURNY,M.
MLLERANDL.
SCAPOZZA.
Hyaluronicacid-antioxydantsconjugatesandtheirusesUSPat.
EFSID14508328,(DECEMBER2012)