Sangwon Lee, PhD
Assistant Professor of PharmacologyCards
About
Titles
Assistant Professor of Pharmacology
Appointments
Pharmacology
Assistant ProfessorPrimary
Other Departments & Organizations
Education & Training
- Associate Research Scientist
- Yale School of Medicine (2018)
- Postdoctoral Associate
- Yale School of Medicine (2012)
- PhD
- University of California, San Diego, Chemistry and Biochemistry (2007)
- MS
- Konkuk University, Chemistry (1998)
- BS
- Konkuk University, Chemistry (1996)
Research
Publications
Featured Publications
Isoform-specific inhibition of FGFR signaling achieved by a de-novo-designed mini-protein
Park JS, Choi J, Cao L, Mohanty J, Suzuki Y, Park A, Baker D, Schlessinger J, Lee S. Isoform-specific inhibition of FGFR signaling achieved by a de-novo-designed mini-protein. Cell Reports 2022, 41: 111545. PMID: 36288716, PMCID: PMC9636537, DOI: 10.1016/j.celrep.2022.111545.Peer-Reviewed Original ResearchConceptsFibroblast growth factor receptorC isoformsFibroblast growth factor ligandsLigand-binding regionSilico design strategyIsoform-specific inhibitionGrowth factor ligandsAlternative splicingCellular signalingRegulated processGrowth factor receptorDevelopment of therapeuticsFGFR isoformsFactor ligandCellular analysisFactor receptorMechanistic insightsKlotho proteinSpecific interactionsMB7Distinct subsetsHigh affinitySplicingSignalingFGFDesign of protein-binding proteins from the target structure alone
Cao L, Coventry B, Goreshnik I, Huang B, Sheffler W, Park JS, Jude KM, Marković I, Kadam RU, Verschueren KHG, Verstraete K, Walsh STR, Bennett N, Phal A, Yang A, Kozodoy L, DeWitt M, Picton L, Miller L, Strauch EM, DeBouver ND, Pires A, Bera AK, Halabiya S, Hammerson B, Yang W, Bernard S, Stewart L, Wilson IA, Ruohola-Baker H, Schlessinger J, Lee S, Savvides SN, Garcia KC, Baker D. Design of protein-binding proteins from the target structure alone. Nature 2022, 605: 551-560. PMID: 35332283, PMCID: PMC9117152, DOI: 10.1038/s41586-022-04654-9.Peer-Reviewed Original ResearchConceptsDe novo designStructures of ligand-occupied β-Klotho complexes reveal a molecular mechanism underlying endocrine FGF specificity and activity
Kuzina ES, Ung PM, Mohanty J, Tome F, Choi J, Pardon E, Steyaert J, Lax I, Schlessinger A, Schlessinger J, Lee S. Structures of ligand-occupied β-Klotho complexes reveal a molecular mechanism underlying endocrine FGF specificity and activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 7819-7824. PMID: 30944224, PMCID: PMC6475419, DOI: 10.1073/pnas.1822055116.Peer-Reviewed Original ResearchConceptsFGF receptorsPleiotropic cellular responsesFibroblast growth factor (FGF) familyPrimary high-affinity receptorsKlotho proteinChimeric mutantsGrowth factor familyCatalytic subunitFGFR functionRegulatory interactionsTerminal tailPleiotropic cellular effectsFactor familyP motifS motifExtracellular domainMolecular mechanismsIntracellular signalingCellular responsesSame binding siteCellular effectsGeneral mechanismEndocrine FGFsBinary complexBinding sitesStructures of β-klotho reveal a ‘zip code’-like mechanism for endocrine FGF signalling
Lee S, Choi J, Mohanty J, Sousa LP, Tome F, Pardon E, Steyaert J, Lemmon MA, Lax I, Schlessinger J. Structures of β-klotho reveal a ‘zip code’-like mechanism for endocrine FGF signalling. Nature 2018, 553: 501-505. PMID: 29342135, PMCID: PMC6594174, DOI: 10.1038/nature25010.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCrystallography, X-RayExtracellular SpaceFibroblast Growth Factor-23Fibroblast Growth FactorsGlycoside HydrolasesHEK293 CellsHumansKlotho ProteinsLigandsMembrane ProteinsModels, MolecularProtein BindingProtein DomainsReceptors, Fibroblast Growth FactorSignal TransductionSubstrate SpecificityInhibition of ErbB3 by a monoclonal antibody that locks the extracellular domain in an inactive configuration
Lee S, Greenlee EB, Amick JR, Ligon GF, Lillquist JS, Natoli EJ, Hadari Y, Alvarado D, Schlessinger J. Inhibition of ErbB3 by a monoclonal antibody that locks the extracellular domain in an inactive configuration. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 13225-13230. PMID: 26460020, PMCID: PMC4629334, DOI: 10.1073/pnas.1518361112.Peer-Reviewed Original ResearchConceptsAllosteric mechanismExtracellular domainUnique allosteric mechanismFormation of heterodimersReceptor tyrosine kinasesEGF receptor familyTyrosine kinase domainStructure-based designPseudo-kinaseKinase domainLigand-dependent mechanismInactive conformationTyrosine kinaseInactive configurationReceptor familyFamily activationErbB3 activationErbB3KinaseErbB2ErbB4Family membersDomainActivationHeterodimerization
2024
Modulation of FGF pathway signaling and vascular differentiation using designed oligomeric assemblies.
Edman NI, Phal A, Redler RL, Schlichthaerle T, Srivatsan SR, Ehnes DD, Etemadi A, An SJ, Favor A, Li Z, Praetorius F, Gordon M, Vincent T, Marchiano S, Blakely L, Lin C, Yang W, Coventry B, Hicks DR, Cao L, Bethel N, Heine P, Murray A, Gerben S, Carter L, Miranda M, Negahdari B, Lee S, Trapnell C, Zheng Y, Murry CE, Schweppe DK, Freedman BS, Stewart L, Ekiert DC, Schlessinger J, Shendure J, Bhabha G, Ruohola-Baker H, Baker D. Modulation of FGF pathway signaling and vascular differentiation using designed oligomeric assemblies. Cell 2024, 187: 3726-3740.e43. PMID: 38861993, DOI: 10.1016/j.cell.2024.05.025.Peer-Reviewed Original Research
2023
Cryo-EM analyses of KIT and oncogenic mutants reveal structural oncogenic plasticity and a target for therapeutic intervention
Krimmer S, Bertoletti N, Suzuki Y, Katic L, Mohanty J, Shu S, Lee S, Lax I, Mi W, Schlessinger J. Cryo-EM analyses of KIT and oncogenic mutants reveal structural oncogenic plasticity and a target for therapeutic intervention. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2300054120. PMID: 36943885, PMCID: PMC10068818, DOI: 10.1073/pnas.2300054120.Peer-Reviewed Original ResearchConceptsOncogenic KIT mutantsStem cell factorKIT mutantsHomotypic contactsCryo-EM analysisUnexpected structural plasticityLigand stem cell factorElectron microscopy structural analysisReceptor tyrosine kinase KITOncogenic mutantsHematopoietic stem cellsKIT dimerizationTyrosine kinase KITD5 regionPlasma membraneMutational analysisMutantsExtracellular domainGerm cellsHuman cancersSomatic gainCell factorStructural plasticityStem cellsKinase KIT
2020
FGF23 contains two distinct high-affinity binding sites enabling bivalent interactions with α-Klotho
Suzuki Y, Kuzina E, An SJ, Tome F, Mohanty J, Li W, Lee S, Liu Y, Lax I, Schlessinger J. FGF23 contains two distinct high-affinity binding sites enabling bivalent interactions with α-Klotho. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 31800-31807. PMID: 33257569, PMCID: PMC7749347, DOI: 10.1073/pnas.2018554117.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCalcinosisCell MembraneFibroblast Growth Factor-23Fibroblast Growth FactorsGlucuronidaseHEK293 CellsHumansHyperostosis, Cortical, CongenitalHyperphosphatemiaImmunoglobulin Fc FragmentsKlotho ProteinsMutationOsteomalaciaProtein BindingProtein DomainsProtein MultimerizationRecombinant Fusion ProteinsRickets, HypophosphatemicConceptsFGF receptorsTotal internal reflection fluorescence microscopyChimeric receptor moleculesReflection fluorescence microscopyBinding sitesDisulfide bridge formationCritical metabolic processesMAPK responseCytoplasmic domainGrowth factor familyTerminal tailFactor familyKinase activationSimilar binding affinitiesExtracellular domainFGFR1 activationTandem repeatsMetabolic processesDisulfide bridgesCell surfaceDistinct ligandsCell membraneFluorescence microscopyDistinct high-affinity binding sitesPhosphate homeostasis
2017
Tylophorine Analogs Allosterically Regulates Heat Shock Cognate Protein 70 And Inhibits Hepatitis C Virus Replication
Wang Y, Lee S, Ha Y, Lam W, Chen SR, Dutschman GE, Gullen EA, Grill SP, Cheng Y, Fürstner A, Francis S, Baker DC, Yang X, Lee KH, Cheng YC. Tylophorine Analogs Allosterically Regulates Heat Shock Cognate Protein 70 And Inhibits Hepatitis C Virus Replication. Scientific Reports 2017, 7: 10037. PMID: 28855547, PMCID: PMC5577180, DOI: 10.1038/s41598-017-08815-z.Peer-Reviewed Original ResearchConceptsHepatitis C virus replicationC virus replicationTylophorine analogsHCV replicationHeat shock cognate protein 70HCV RNAShock cognate protein 70Inhibits Hepatitis C Virus ReplicationVirus replicationProtein 70Anti-HCV activityHCV replication complexPotent inhibitory activityExhibit potent inhibitory activityInhibitory activityATPase activityArthritisInflammationLupusReplicationActivityCancerHsc70
2015
FGF1 and FGF19 reverse diabetes by suppression of the hypothalamic–pituitary–adrenal axis
Perry RJ, Lee S, Ma L, Zhang D, Schlessinger J, Shulman GI. FGF1 and FGF19 reverse diabetes by suppression of the hypothalamic–pituitary–adrenal axis. Nature Communications 2015, 6: 6980. PMID: 25916467, PMCID: PMC4413509, DOI: 10.1038/ncomms7980.Peer-Reviewed Original ResearchMeSH KeywordsAcetyl Coenzyme AAdrenocorticotropic HormoneAnimalsCorticosteroneDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1Fibroblast Growth Factor 1Fibroblast Growth FactorsGlucoseHypothalamo-Hypophyseal SystemInjections, IntraventricularInsulinLipolysisLiverMalePituitary-Adrenal SystemPyruvate CarboxylaseRats, Sprague-DawleyConceptsHepatic acetyl-CoA contentFibroblast growth factor 1Whole-body lipolysisHepatic glucose productionAcetyl-CoA contentGlucose productionAwake rat modelRecombinant fibroblast growth factor 1CoA contentIntra-arterial infusionGlucose-lowering effectType 1 diabetesGrowth factor-1Mechanism of actionReverse diabetesDiabetic rodentsICV injectionIntracerebroventricular injectionPlasma ACTHHPA axisAdrenal axisRat modelGlucose metabolismCorticosterone concentrationsFGF19