2023
ALK inhibitors increase ALK expression and sensitize neuroblastoma cells to ALK.CAR-T cells
Bergaggio E, Tai W, Aroldi A, Mecca C, Landoni E, Nüesch M, Mota I, Metovic J, Molinaro L, Ma L, Alvarado D, Ambrogio C, Voena C, Blasco R, Li T, Klein D, Irvine D, Papotti M, Savoldo B, Dotti G, Chiarle R. ALK inhibitors increase ALK expression and sensitize neuroblastoma cells to ALK.CAR-T cells. Cancer Cell 2023, 41: 2100-2116.e10. PMID: 38039964, PMCID: PMC10793157, DOI: 10.1016/j.ccell.2023.11.004.Peer-Reviewed Original ResearchConceptsALK inhibitorsALK expressionChimeric antigen receptor TBest tumor antigensPromising clinical activityExpression of ALKMost normal tissuesHematologic malignanciesClinical activityMost neuroblastomasAnaplastic lymphoma kinase (ALK) receptorTherapeutic successTumor antigensPotent efficacySolid tumorsTherapeutic efficacyNeuroblastomaTumor growthOncogenic driversNeuroblastoma cellsNormal tissuesALKKinase receptorsMonotherapyInhibitorsMassively parallel base editing to map variant effects in human hematopoiesis
Martin-Rufino J, Castano N, Pang M, Grody E, Joubran S, Caulier A, Wahlster L, Li T, Qiu X, Riera-Escandell A, Newby G, Al'Khafaji A, Chaudhary S, Black S, Weng C, Munson G, Liu D, Wlodarski M, Sims K, Oakley J, Fasano R, Xavier R, Lander E, Klein D, Sankaran V. Massively parallel base editing to map variant effects in human hematopoiesis. Cell 2023, 186: 2456-2474.e24. PMID: 37137305, PMCID: PMC10225359, DOI: 10.1016/j.cell.2023.03.035.Peer-Reviewed Original ResearchConceptsHuman hematopoiesisVariant effectsNon-coding variantsDisease-associated variantsSingle-cell genotypingHuman hematopoietic stemFetal hemoglobin expressionHigh-throughput variantGenome engineeringSequencing readoutHematopoietic differentiationFunctional screenHemoglobin expressionDifferentiation stateDefines mechanismsHematopoietic stemPrimary cellsGenetic variantsProgenitor cellsSpecific mutationsDiverse diseasesHuman physiologyRich phenotypingHematopoiesisImmunotherapy approachesRAMIHM generates fully human monoclonal antibodies by rapid mRNA immunization of humanized mice and BCR-seq
Ren P, Peng L, Yang L, Suzuki K, Fang Z, Renauer P, Lin Q, Bai M, Li T, Clark P, Klein D, Chen S. RAMIHM generates fully human monoclonal antibodies by rapid mRNA immunization of humanized mice and BCR-seq. Cell Chemical Biology 2023, 30: 85-96.e6. PMID: 36640761, PMCID: PMC9868106, DOI: 10.1016/j.chembiol.2022.12.005.Peer-Reviewed Original ResearchConceptsHuman monoclonal antibodyHumanized miceMonoclonal antibodiesMemory B cell populationsHumanized transgenic miceBroad antibody responseB cell populationsG protein-coupled receptor targetsNeutralizing antibodiesPeripheral bloodAntibody responseImmunotherapy targetClinical vaccinesPlasma BCell sequencingTransgenic miceImmunization methodReceptor targetsAntibodiesMiceCell populationsHigh potencyImmunizationHigh rateAntibody discovery
2021
Structural basis for ligand reception by anaplastic lymphoma kinase
Li T, Stayrook SE, Tsutsui Y, Zhang J, Wang Y, Li H, Proffitt A, Krimmer SG, Ahmed M, Belliveau O, Walker IX, Mudumbi KC, Suzuki Y, Lax I, Alvarado D, Lemmon MA, Schlessinger J, Klein DE. Structural basis for ligand reception by anaplastic lymphoma kinase. Nature 2021, 600: 148-152. PMID: 34819665, PMCID: PMC8639777, DOI: 10.1038/s41586-021-04141-7.Peer-Reviewed Original Research
2019
H2A.Z facilitates licensing and activation of early replication origins
Long H, Zhang L, Lv M, Wen Z, Zhang W, Chen X, Zhang P, Li T, Chang L, Jin C, Wu G, Wang X, Yang F, Pei J, Chen P, Margueron R, Deng H, Zhu M, Li G. H2A.Z facilitates licensing and activation of early replication origins. Nature 2019, 577: 576-581. PMID: 31875854, DOI: 10.1038/s41586-019-1877-9.Peer-Reviewed Original ResearchConceptsOrigin recognition complexHistone variant H2A.ZEarly replication originsReplication originsVariant H2A.ZReplication timingChromatin-based regulatory mechanismsEarly replication timingGenome-wide studiesNascent DNA strandsH2A.Z resultsNucleosome bindsDNA replicationH2A.ZHistone H4Cell cycle1Precise duplicationRegulated processDNA sequencesRegulatory mechanismsHeLa cellsDNA strandsORC1Firing efficiencyGenome