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Explore the cutting-edge research on tumor angiogenesis, HIF regulation, epigenetic control, and novel angiogenic inhibitors by Dr. You Mie Lee. Discover the latest developments in endothelial progenitor cells and therapeutic approaches in angiogenic diseases.
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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