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◎ R e s e a r c h Fiel d : Molecular P athophys i o l ogy PowerPoint Presentation
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◎ R e s e a r c h Fiel d : Molecular P athophys i o l ogy
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  1. 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

  2. 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

  3. 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

  4. AngiogenicBalance

  5. Tumorgrowthandangiogenesis

  6. Anti-angiogenictherapy

  7. 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

  8. VEGFsignalingpathway

  9. Hypoxia(EF5) normoxia CD31(EC) EF-5(hypoxicmarker), WeinbergR,TheBiologyofCancer,2007

  10. Hypoxicmicroenvironmentintumor Nature407:249-257,2000

  11. RoleofHIF-1incancercellresponses Chemoresistance MDR1 MT-IIA CA9 JMolMed(2007)85:1301-1307

  12. Angiogenesis Hypoxia (저산소미세환경) HIF-1 10billion$/year(Roche) VEGF dormant Mutation Regressionofcancer Secretionofangiogenicfactors Rapidgrowthofcancer CarmelietandJain.Nature.2000 =Proangiogenicfactor,eg.VEGF =Angiogenicinhibitor

  13. Vasculogenesisvs.Angiogenesis Vasculogenesis Angiogenesis

  14. 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

  15. ResearchApproach MechanismofHIFexpression Hypoxia-inducedgenes -DNAchip -Proteomics ComputerAnalysis Genefinding HIF A,B,C,.…X <Epigeneticregulation> Findingofregulatorymolecules ConfirmwithK/OorK/Danimals Functionalanalysis