2023
Repurposing GSK3B Small Molecule Inhibitors for Refractory Lymphoid Malignancies
Cosgun K, Robinson M, Oulghazi S, Xu L, Xiao G, Chan L, Lee J, Kume K, Leveille E, Arce D, Khanduja D, Feldhahn N, Song J, Chan W, Chen J, Taketo M, Schjerven H, Jellusova J, Kothari S, Davids M, Müschen M. Repurposing GSK3B Small Molecule Inhibitors for Refractory Lymphoid Malignancies. Blood 2023, 142: 2818. DOI: 10.1182/blood-2023-190522.Peer-Reviewed Original ResearchFavorable safety profileSmall molecule inhibitorsT-lymphoid malignancyΒ-catenin degradationLymphoid malignanciesΒ-cateninInteractome studiesSafety profileClinical trialsMolecule inhibitorsLow nanomolar concentrationsΒ-catenin accumulationSolid tumorsRefractory B-cell malignanciesCell deathPK/PD profilesZinc finger proteinRefractory lymphoid malignanciesChIP-seq analysisPhase 2 trialMYC target genesT-cell lymphomaColony formationRapid nuclear accumulationWnt/β-catenin pathwayComputational Discovery and Validation of NAD+ Biosynthesis As Unique Vulnerability in B-Lymphoid Malignancies
Li Q, Robinson M, Leveille E, Zhang C, Sun R, Cheng Z, Kume K, Cosgun K, Kothari S, Khanduja D, Nakada D, Müschen M. Computational Discovery and Validation of NAD+ Biosynthesis As Unique Vulnerability in B-Lymphoid Malignancies. Blood 2023, 142: 418. DOI: 10.1182/blood-2023-190269.Peer-Reviewed Original ResearchSmall molecule inhibitorsDrug discovery toolNAMPT inhibitorsCompound screenCell type-specific targetsCell linesMolecule inhibitorsPurine/pyrimidine metabolismTumor cell linesEnergy metabolismSalvage biosynthesis pathwaySolid tumor cell linesB cell developmentCellular energy metabolismB cell signalingAmino acid metabolismCell cycle arrestDiscovery toolDepletion of metabolitesBiosynthesis pathwayCompetitive fitnessRate-limiting enzymeNAMPT deletionConditional mouse modelEnergy stressGenetic Knockin Approaches to Reconstructing DLBCL-Subtypes from Human Germinal Center B-Cells
Khanduja D, Robinson M, Arce D, Klemm L, Leveille E, Kothari S, Caeser R, Hodson D, Müschen M. Genetic Knockin Approaches to Reconstructing DLBCL-Subtypes from Human Germinal Center B-Cells. Blood 2023, 142: 1627. DOI: 10.1182/blood-2023-190634.Peer-Reviewed Original ResearchSecondary lymphoid organsGerminal center B cellsMYD88 L265P mutationLymphoid organsLymph nodesB cellsL265P mutationHuman germinal center B cellsDLBCL subtypesNSG miceTonsillar germinal center B cellsLymphoma developmentPreclinical testingLymphoid tissue inducer cellsTransgenic expressionPoor clinical outcomeWild-type mutationsGenetic mouse modelsExon 5GC B cellsNBSGW miceClinical outcomesLTi cellsLymphoid folliclesInducer cells
2022
Genetic Modeling of B-cell State Transitions for Rational Design of Lymphoma Therapies.
Leveille E, Kothari S, Müschen M. Genetic Modeling of B-cell State Transitions for Rational Design of Lymphoma Therapies. Blood Cancer Discovery 2022, 4: 8-11. PMID: 36534735, PMCID: PMC9816816, DOI: 10.1158/2643-3230.bcd-22-0180.Commentaries, Editorials and Letters