2023
Computational 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 stress
2020
Pevonedistat, a NEDD8‐activating enzyme inhibitor, induces apoptosis and augments efficacy of chemotherapy and small molecule inhibitors in pre‐clinical models of diffuse large B‐cell lymphoma
Torka P, Mavis C, Kothari S, Belliotti S, Gu J, Sundaram S, Barth M, Hernandez‐Ilizaliturri F. Pevonedistat, a NEDD8‐activating enzyme inhibitor, induces apoptosis and augments efficacy of chemotherapy and small molecule inhibitors in pre‐clinical models of diffuse large B‐cell lymphoma. EJHaem 2020, 1: 122-132. PMID: 33073261, PMCID: PMC7566777, DOI: 10.1002/jha2.2.Peer-Reviewed Original ResearchActivated B cellsPre-clinical modelsSmall molecule inhibitorsClass NEDD8-activating enzyme (NAE) inhibitorEnzyme inhibitorsSCID mouse xenograft modelDiffuse large B-cell lymphomaCell linesLarge B-cell lymphomaActivity of cytarabineCytotoxic chemotherapy agentsFurther clinical studiesB-cell lymphomaViable therapeutic strategyMouse xenograft modelMolecule inhibitorsB-cell lymphoma cell linesDLBCL cell linesGCB-DLBCL cell linesLarge B-cell lymphoma cell linesAugments efficacyChemotherapy agentsClinical studiesLymphoma cell linesMonotherapy controls
2018
Effects of Proteasome Inhibition in the Anti-Tumor Activity of Venetoclax in Mantle Cell Lymphoma Pre-Clinical Models
Kothari S, Mavis C, Gu J, Hernandez-Ilizaliturri F. Effects of Proteasome Inhibition in the Anti-Tumor Activity of Venetoclax in Mantle Cell Lymphoma Pre-Clinical Models. Blood 2018, 132: 2942. DOI: 10.1182/blood-2018-99-116510.Peer-Reviewed Original ResearchMantle cell lymphomaAnti-tumor activityPre-clinical modelsRefractory mantle cell lymphomaB-cell lymphoma patientsPrimary tumor cellsMCL cell linesCell cycle regulatory proteinsResistant cell linesProteasome inhibitorsHBL-2 cellsLymphoma patientsCycle regulatory proteinsSCID miceSCID animalsCell linesAutologous stem cell rescueTumor cellsHigh-dose chemotherapyStem cell rescueSignificant anti-tumor activitySynergistic activityNovel therapeutic strategiesNovel proteasome inhibitorSelective BCL-2 inhibitor