翻譯醫(yī)學(xué)Marc Shuman翻譯醫(yī)學(xué)Marc Shuman

iumonClinicalandderofUCSFUCBerkeleyMastersinTranslationalforfor?AssociateEditorJournalofClinicalInvestigation1989-1994?AdvisoryBoard?CellWorksInc.?InterpretaInc.?AndesBionova,Inc.ialsialsTheTranslationalResearchParadigmClinicClinic/HospitalIDENTIFYNEEDSsPharmaPharma/Biotech/DeveClinic/HospitalPhaseIII?Antibodies?Smallmolecules?Cellulartherapeutics(Laborious.TimeconsumingPurity+/-)Cloning:Earlydays?GrowthHormone(UCSF-Genentech)1976?G-CSFAMGEN1985?AllanJ.Erslev(ThomasJeffersonMedicalsredbloodesearcheratcenseditPOia?Clonedin1985byAMGEN?1989approvedbyFDAforadministrationwork.?Aranesp+Epogengeneratedsalesof~5s0204060802000-20151990's1980's1970'snicaluse?Endocrinedisorders(hormonedeficiencies)InsulinanalogsDiabetesmellitus??HemophiliaB?Proteintherapeuticsthatderivetheirspecificityandfunctionfromtheirstructure.TherapeuticMetabolicenzymedeficiency?a-Gluco-cerebrosidase2Gaucher’sdisease?MyozymePompedisease(glycogen?LaronidaseHurlerandHurler-Scheiedisease?Elaprase?GalsulphaseRecombinantProteintherapeuticsAugmentingaKnownPathway?Erythropoietin,Anemiaofchronicdisease,renalfailure,myleodysplasia,?GranulocytecolonystimulatingfactorG-CSFNeutropeniainpost-chemotherapy,bone-marrowtransplantation?Granulocyte-macrophagecolonystimulatingfactor(GM-CSF)Leukopenia,myeloidreconstitutionpost-bone-marrowtransplantation?Thrombopoietinthrombocytopaeniaaftermyelosuppressivechemotherapy;ITP?Humanfollicle-stimulatinghormone(FsH)Assistedreproduction?Humanchorionicgonadotropin(HcG)Assistedreproduction?Lutropin-LuverisInfertilitywithluteinizinghormonedeficiencyeRecombinantantibodies?Cancer,examples–Anti-Her2(2001)Breast–Anti-EGFR2009Lung,colon?Autoimmunediseases,example?Anti-TNFalpha(1994)–Rheumatoidarthritis;Crohn’sdisease;Ulcerativecolitis;AnkylosingspondylitisdcylaGenentechIncAntibodydirectedanti-cancerdrugsonrSMALLMOLECULES?KinaseInhibitorsTKIsoperatebyseveraldifferentmechanisms:mpetitionwithATPthephosphorylatingentity,thesubstrateorbothactinanallostericfashion,i.e.,bindtoasiteoutsidetheactivesite,affectingitsactivitybyconformationalchanges.?Ubiquitylation?Degradation.?sinekinaseshavebeengeneratedandareeffectiveanti-canceragents.?Basedonthiswork,imatinibwasdevelopedagainstchronicmyelogenousleukemia(CML).?LatergefitinibanderlotinibinhibitorsoftheEGF?Sunitinib,aninhibitoroftheforFGF,PDGFandVEGFreceptorsisalsobasedonstudiesofTKIsofVEGFreceptors.nhibitorsespeciallyTKIsonAbltyrosinekinaseCrystalstructureofthesecondgenerationBcr-Abltyrosine-kinaseinhibitornilotinib(red)incomplexwithanAblkinasedomain(blue).transplantation(hematopoieticstemsEDonalThomasCellTherapeutics?ChronicB-celllymphocyticleukemia(CLL)?Acutelymphoblasticleukemia(ALL)itAsksphysicianifhecanuseit.Doc,Canyouusethis?arethereisaneedforanewdevice.-Mechanicalventricularassistdevices(VAD)----Cardioablation(arrhythmias)?Thepresent?ysture?Indication:Organfailure?Problem-therearen’tenoughorganstoemand?USA?In2011,morethan110,000peoplewereontinglistforanorganAnaverageofnearlydieeverydaywhilewaiting.?Morethan16,000kidneyin?Thewaitcanbelong(verylong!).Innearly000peoplewereon?Jaw?Skull?Skin?Trachea(congenitalatresia)sselsinmiceandothersmallanimals?ThebiggestchallengeistogetthecellstoloodbodilyfluidsofRX;Prognosis.–IdeasfromacademiaorPharmaDevelopment:Academia?Pharma?Requirevalidationusuallyclinicaltrials.Usuallyacademiafinancedbyacademia.FDAApprovallizationsourceofforcompanylinicalTranslationalSciencetosupporttranslationalresearch.UCSFawarded120millionUS$$bya5–yearNIHaward.staffsupportedbyCTSIresourcesandservices.Facilitatesthetranslationofresearchtoimprovementsinpatientandcommunityhealth.Campus-wideinstitutewithscientificleadersatitshelm.ionandteambuilding?CTSIintramuralcompetitiveprogramprovidingfundingandconsultationto