Kadriye Nehir Cosgun, PhD
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Targeting β-catenin degradation with GSK3β inhibitors induces cell death in acute lymphoblastic leukemia
Cosgun K, Jumaa H, Robinson M, Cheng Z, Oulghazi S, Kume K, Fonseca Arce D, Agadzhanian N, Kistner K, Leveille E, Drivet E, Yu F, Qian Z, Song J, Chan W, Xu L, Xiao G, Taketo M, Kothari S, Davids M, Schjerven H, Jellusova J, Müschen M. Targeting β-catenin degradation with GSK3β inhibitors induces cell death in acute lymphoblastic leukemia. Nature Cancer 2026, 7: 150-168. PMID: 41507538, PMCID: PMC12858398, DOI: 10.1038/s43018-025-01093-z.Peer-Reviewed Original ResearchConceptsProtein degradationCell deathProtein degradation machineryAcute lymphoblastic leukemiaGlycogen synthase kinase 3bB-ALLXenograft model in vivoDegradation machineryCRISPR screensMyc repressionProteasomal degradationHuman B-ALLLymphoblastic leukemiaPatient-derived xenograft models in vivoRefractory B-cell malignanciesB-cateninB-cell acute lymphoblastic leukemiaAcute cell deathWnt signalingGSK3BB-cell malignanciesMechanistic targetProteinMYCModel in vivoIdentification of NAE1-dependent β-catenin neddylation as selective vulnerability in B-cell malignancies
Cosgun K, Ito T, Robinson M, Fera E, Oulghazi S, Feng Y, Forward J, Yin T, Xin G, Chen S, Davids M, Müschen M. Identification of NAE1-dependent β-catenin neddylation as selective vulnerability in B-cell malignancies. Blood 2025, 146: 5042. DOI: 10.1182/blood-2025-5042.Peer-Reviewed Original ResearchB cell selectionCre-mediated deletionCell deathB-cell malignanciesAcute cell deathProteasomal degradationProtein degradationNedd8-E3 ligaseLoss of colony formationMantle cell lymphomaB-cell tumorsB-ALLCRISPR-KO screensCRISPR-mediated deletionB cellsPre-B cell transitionPro- to pre-B cell transitionNext generation sequencingNEDD8-activating enzymeB-cateninB cell developmentHematopoietic reconstitutionCell lymphomaExpression of MYCLeukemia-initiating abilityHarnessing repressive LEF1/β-catenin complexes to overcome drug resistance in chronic lymphocytic leukemia
Cosgun K, Ito T, Robinson M, Fera E, Mishra P, Forward J, Iyer P, Wang L, Vaisitti T, Deaglio S, Buchner M, Xue H, Davids M, Müschen M. Harnessing repressive LEF1/β-catenin complexes to overcome drug resistance in chronic lymphocytic leukemia. Blood 2025, 146: 5659-5659. DOI: 10.1182/blood-2025-5659.Peer-Reviewed Original ResearchNuclear translocation of b-cateninCLL cellsB cellsSolid tumorsB-cateninGSK3B inhibitionRichter transformationLEF1 expressionCLL developmentH3K27ac signalPK/PD profilesClinical trialsNuclear translocationB cell-specific deletionMYC enhancer regionChronic lymphocytic leukemiaB-cell leukemiaMyc repressionNormal B cellsCell deathExpression of MYCWnt/b-catenin signalingIntracellular FACSLymphocytic leukemiaMechanism of actionKit Regulates HSC Engraftment across the Human-Mouse Species Barrier
Cosgun KN, Rahmig S, Mende N, Reinke S, Hauber I, Schäfer C, Petzold A, Weisbach H, Heidkamp G, Purbojo A, Cesnjevar R, Platz A, Bornhäuser M, Schmitz M, Dudziak D, Hauber J, Kirberg J, Waskow C. Kit Regulates HSC Engraftment across the Human-Mouse Species Barrier. Cell Stem Cell 2014, 15: 227-238. PMID: 25017720, DOI: 10.1016/j.stem.2014.06.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineageCrosses, GeneticEnzyme-Linked Immunosorbent AssayFetal BloodGene Expression RegulationHematopoietic Stem Cell TransplantationHematopoietic Stem CellsHumansLymphocytesMiceMice, Inbred C57BLMice, TransgenicMutationRNA, MessengerSpecies SpecificityStem Cell FactorThymocytesTime Factors
2026
BCR::ABL1‐Induced Enhancer Reprogramming Uncovers Hypersensitivity of Ph+B‐ALL Cells to Enhancer‐Targeting Drugs
Ng H, Glaser T, Zhu J, Robinson M, Cosgun K, Malysheva V, Deniz O, Crump N, Helian K, Innes A, Burt R, Sun L, John G, Zhou H, Kaneshige A, Bai L, Wang S, Spivakov M, Müschen M, Feldhahn N. BCR::ABL1‐Induced Enhancer Reprogramming Uncovers Hypersensitivity of Ph+B‐ALL Cells to Enhancer‐Targeting Drugs. Advanced Science 2026, e17231. PMID: 41764406, DOI: 10.1002/advs.202517231.Peer-Reviewed Original ResearchKinase-dependent activationTranscriptional programsB-ALLActivation of STAT5B-lineage leukemiasTranscriptional reprogrammingGenomic lesionsEnhancer reprogrammingKinase activityPoor prognosisCurrent therapiesMalignant transformationHematological cancersEnhancer deregulationKinase inhibitorsCurrent treatmentBlood cancerCancer initiationCancerEnhanced inhibitionEnhancer signaturesBCR::ABL1LesionsEnhanced activityGenesDynamic feedback control of oncogenic tyrosine kinase signaling in acute leukemia
Lee J, Sun R, Kume K, Robinson M, Cheng Z, Cosgun K, Ma N, Hurtz C, Geng H, Luger S, Litzow M, Paietta E, Chen J, Vaidehi N, Müschen M. Dynamic feedback control of oncogenic tyrosine kinase signaling in acute leukemia. Science Signaling 2026, 19: eadw5054. PMID: 41666265, PMCID: PMC12924454, DOI: 10.1126/scisignal.adw5054.Peer-Reviewed Original ResearchConceptsOncogenic tyrosine kinase signalingTyrosine kinase signalingPatient-derived xenograftsKinase signalingAcute leukemiaNatural killerInterleukin-2Tyrosine kinaseLeukemia cellsLeukemia-initiating capacityActivation of tyrosine kinasesGlobal phosphoproteome analysisOncogenic tyrosine kinasesPhosphatase activityInteractome analysisModels of acute leukemiaAntibody-drug conjugatesAcute leukemia cellsPhosphoproteomic analysisClonal fitnessRefractory leukemiaTransplant recipientsInhibitory phosphatasesMyeloid leukemiaT cells
2025
Alternating cycles of quiescent and proliferative cell states determine stemness and leukemia-initiation capacity in acute lymphoblastic leukemia
Cheng Z, Kume K, Shi R, Robinson M, Cosgun K, Bao Y, Chen S, Mishra P, Bewersdorf J, Xu M, Müschen M. Alternating cycles of quiescent and proliferative cell states determine stemness and leukemia-initiation capacity in acute lymphoblastic leukemia. Blood 2025, 146: 1485-1485. DOI: 10.1182/blood-2025-1485.Peer-Reviewed Original ResearchLeukemia-initiating cellsB-ALL cellsCell state transitionsAcute myeloid leukemiaLeukemia-initiating cell populationProliferative cell statesCell statesB-ALLFusion proteinTime-lapse imagingDry massKnockin alleleClonal hierarchyIntegrated ChIP-seqCatabolic metabolismMultiplex immunofluorescenceGene expression studiesDrug resistanceCellular dry massTime-lapse fluorescence imagingQuiescent cell stateLeukemia-initiating potentialChIP-seqDegron systemProtein synthesis pathwaysTargeted hyperactivation of oncogenic STAT5-signaling in acute lymphoblastic leukemia
Kume K, Cheng Z, Lin J, Xu L, Xiao G, Robinson M, Leveille E, Bramson E, Cosgun K, Geng H, Heinäniemi M, Graeber T, Abkowitz J, Chi H, Alexander W, Chiarle R, Leonard W, Müschen M. Targeted hyperactivation of oncogenic STAT5-signaling in acute lymphoblastic leukemia. Blood 2025, 146: 433-433. DOI: 10.1182/blood-2025-433.Peer-Reviewed Original ResearchLoss-of-functionB-ALL cellsLeukemia-initiating capacityCell statesER stressColony formationLoss of colony formationLeukemia cellsAmino acid metabolic pathwaysActivation of MYCExpression levelsGenetic deletionProliferative cell statesTime-lapse experimentsInhibitors of JAK2Oncogenic tyrosine kinasesActivation of BCL6Autophagosome biogenesisPtdEtn synthesisBCL6 target genesTCA cycleGene setsSTAT5 regulationCell-statesTranscriptional programsTargeting β-catenin nuclear export and protein degradation in high-risk acute lymphoblastic leukemia
Forward J, Cosgun K, Fera E, Bhojwani D, Teachey D, Müschen M. Targeting β-catenin nuclear export and protein degradation in high-risk acute lymphoblastic leukemia. Blood 2025, 146: 3371-3371. DOI: 10.1182/blood-2025-3371.Peer-Reviewed Original ResearchCargo proteinsLeukemia cell deathNuclear exportProtein degradationB-ALL cellsCell deathAcute lymphoblastic leukemia cellsNuclear localizationAcute lymphoblastic leukemiaXPO1 inhibitionT-ALLProtein degradation mechanismsLeukemia cell survivalAdvanced clinical developmentB-cateninGain-of-function mutationsGain-of-functionT-ALL cellsInhibitor of XPO1T-ALL xenograftsWestern blottingCRISPR engineeringCancer cell linesDegradation complexExpression reportersApoptotic rewiring via PI3K hyperactivation as a therapeutic strategy in B-cell malignancies
Martindale S, Leveille E, Wang J, Ito T, Cosgun K, Davids M, Müschen M. Apoptotic rewiring via PI3K hyperactivation as a therapeutic strategy in B-cell malignancies. Blood 2025, 146: 437-437. DOI: 10.1182/blood-2025-437.Peer-Reviewed Original ResearchBCL2 dependencyBcl-xLCell deathMCL cell linesB-cell malignanciesPI3K hyperactivationCell linesCaspase inhibitor Z-VAD-FMKPan-caspase inhibitor Z-VAD-FMKInhibitor Z-VAD-FMKAnti-apoptotic dependencyDynamic BH3 profilingCaspase-dependent mechanismZ-VAD-FMKBCL2 inhibitionCRISPR knockout screenBCL2 inhibitor venetoclaxSynthetic lethal genesNegative selectionAnti-apoptotic protein Bcl2Whole-genome CRISPR knockout screenB-ALLPharmacological inhibitionB cellsCompetitive growth assays
Academic Achievements & Community Involvement
News
News
- February 10, 2026
Yale Study Identifies a New Class of Drug Targets for Aggressive Leukemia
- January 08, 2026
Yale-Led Study Identifies a New Target for Treating Acute Leukemia
- December 09, 2025
Yale research advances presented at American Society of Hematology annual meeting
- February 26, 2025
Celebrating Yale Cancer Center Faculty, Research Scientists