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Lab of V as c ular Net w ork Res e arch. P r o f . Y o u Mi e L e e, Ph.D. ◎ R e s e a r c h Fiel d : Molecular P athophys i o l ogy Ca n c er Biolog y , Angiogen i c Dis e a s e s ◎ P r e s e n t - Dean , P r o fe ss o r , K NU, Colle g e o f Pharmacy
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Labof VascularNetworkResearch Prof.YouMieLee,Ph.D • ◎ ResearchField:MolecularPathophysiology • CancerBiology,AngiogenicDiseases • ◎ Present-Dean,Professor,KNU,CollegeofPharmacy • Chairperson,KSMCB(KoreaSocMol&CellBiol) • Chairperson,VSMO(VascularSciMediOrg) • -PI,NationalBasicResearchLab(VascularHomeostasisRegulation) ◎ Career -Education :SeoulNationalUniv.CollegeofPharmacy,Bachelor/Master/Ph.D -MeetingSociety:KSPharm,KSMCB,AACR,KSBMB,etc -Research :TokyoMedicalandDentalUniversity,HarvardMedicalSchool, Children’shospital,Researchfellow,SNUResearchprofessor :KNUfacultymeetingmember,Women’sBioscienceForumchairperson nominatedbyMarquisWho’s WhointheWorld(2009-present) -Services,etc
ResearchInterest http://pharmacy.knu.ac.kr/vnrl/ • 1Tumorangiogenesisanditsinhibitors • RegulationmechanismofHIF • InhibitionofHIF-mediatedgeneexpression • Developmentofnovelangiogenicinhibitors • Epigeneticregulationinangiogenesis • Epigeneticcontroloftumorsuppressors • Epigeneticmodulatorstorestoretheexpressitumorsuppressortoinhibitangiogenesis Geneticallyengineeredzebrafish onof • Endothelialprogenitorcells(EPC) • DifferentiationofEPCsderivedfrombonemarrow(BM)andcordblood • TherapeuticapproachtoutilizeEPCsinangiogenicdiseases • InhibitionofvasculogenicprocessfromBMintumorangiogenesis • <RepresentativePublications> • NatureMed2001;JCellBiochem,2011; • MCT2010;BBA-MCR2010;Oncogene2009,2013, • JBC2012;MNFR2013,NAR2014andetc • Recent3years;40SCIpapers,IF:140
AngiogenicDiseases Boodvessels Atherosclerosis,hemangioma,etc. Skin Warts,Kaposisarcoma, Psoriasis, neoplasm Adiposetissue Obesity Bone, joint Rheumatoidarthritis, synovitis,cancer Brain,nerves, eye Diabeticretinopathy,retinopathyof prematurity, vasculardementia Lymph vessels tumor metastasis Haematopoiesis AIDS, hematologicmalignancy
Angiogenicinhibitors Endogenous(~ 30) Angioarrestin Angiostatin(plasminogenfragment) Cartilage-derivedinhibitor (CDI) Endostatin(collagenXVIIIfragment) Heparinases hCG IL12 Kringle5 (plasminogenfragment) TIMPs Plasminogenativatorinhibitor Retinoids TSP-1 TGF- Naturalsources Treebark Fungi(TNP-470) SharkMuscleandCartilage Seacoral Greentea Herbs Soybean
Hypoxia(EF5) normoxia CD31(EC) EF-5(hypoxicmarker), WeinbergR,TheBiologyofCancer,2007
Hypoxicmicroenvironmentintumor Nature407:249-257,2000
RoleofHIF-1incancercellresponses Chemoresistance MDR1 MT-IIA CA9 JMolMed(2007)85:1301-1307
Angiogenesis Hypoxia (저산소미세환경) HIF-1 10billion$/year(Roche) VEGF dormant Mutation Regressionofcancer Secretionofangiogenicfactors Rapidgrowthofcancer CarmelietandJain.Nature.2000 =Proangiogenicfactor,eg.VEGF =Angiogenicinhibitor
Vasculogenesisvs.Angiogenesis Vasculogenesis Angiogenesis
InhibitorsofHIF-1intumorangiogenesis Growthfactors,RTK, oncogenicactivation Hypoxia Ras PI3K Siah1a/2 ???? AKT Raf PHDs Ub-mediated degradation MEK1/2 mTOR HIF-1 stabilization MAPK pVHL OH HIF-1 synthesisand activity HIF-1 Hsp90 HIF-1 Ub-mediated degradation HIF-1 HIF-1 Target genes p300/CBP HIF-1 HRE Nulceus Angiogenesis,Vasculogenesis
ResearchApproach MechanismofHIFexpression Hypoxia-inducedgenes -DNAchip -Proteomics ComputerAnalysis Genefinding HIF A,B,C,.…X <Epigeneticregulation> Findingofregulatorymolecules ConfirmwithK/OorK/Danimals Functionalanalysis