2023
Pericytes are protective in experimental pneumococcal meningitis through regulating leukocyte infiltration and blood–brain barrier function
Teske N, Dyckhoff-Shen S, Beckenbauer P, Bewersdorf J, Engelen-Lee J, Hammerschmidt S, Kälin R, Pfister H, Brouwer M, Klein M, Glass R, van de Beek D, Koedel U. Pericytes are protective in experimental pneumococcal meningitis through regulating leukocyte infiltration and blood–brain barrier function. Journal Of Neuroinflammation 2023, 20: 267. PMID: 37978545, PMCID: PMC10655320, DOI: 10.1186/s12974-023-02938-z.Peer-Reviewed Original ResearchConceptsModel of pneumococcal meningitisPneumococcal meningitisLeukocyte infiltrationAnimal model of pneumococcal meningitisPrevented blood-brain barrierToll-like receptor inhibitorsDegree of leukocyte infiltrationSerotypes of Streptococcus pneumoniaeUnfavorable disease courseBlood-brain barrier disruptionHuman pericytesExperimental pneumococcal meningitisBlood-brain barrier integrityRegulating leukocyte infiltrationBlood-brain barrier functionRegulation of cerebral blood flowAdult mouse modelInfection in vivoUpregulation of chemokine expressionIncreased cerebral edemaMaintenance of blood-brain barrier integrityBlood-brain barrierCerebral blood flowMouse meningitis modelIn vitro studiesPlasma renalase levels are associated with the development of acute pancreatitis
Wang M, Weiss F, Guo X, Kolodecik T, Bewersdorf J, Laine L, Lerch M, Desir G, Gorelick F. Plasma renalase levels are associated with the development of acute pancreatitis. Pancreatology 2023, 23: 158-162. PMID: 36697349, DOI: 10.1016/j.pan.2023.01.001.Peer-Reviewed Original ResearchConceptsAcute pancreatitisSevere diseasePlasma renalase levelsAcute pancreatitis patientsSevere acute pancreatitisAcute pancreatitis modelPlasma renalaseRenalase levelsSignificant morbidityPancreatitis patientsPlasma levelsHealthy controlsPancreatitis modelPancreatitisPatientsPlasma samplesRenalaseDiseaseNonparametric statistical analysisSecretory proteinsMorbidityStatistical analysisMortalityLevels
2022
Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia
Tanaka A, Nakano T, Nomura M, Yamazaki H, Bewersdorf J, Mulet-Lazaro R, Hogg S, Liu B, Penson A, Yokoyama A, Zang W, Havermans M, Koizumi M, Hayashi Y, Cho H, Kanai A, Lee S, Xiao M, Koike Y, Zhang Y, Fukumoto M, Aoyama Y, Konuma T, Kunimoto H, Inaba T, Nakajima H, Honda H, Kawamoto H, Delwel R, Abdel-Wahab O, Inoue D. Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia. Blood 2022, 140: 875-888. PMID: 35709354, PMCID: PMC9412007, DOI: 10.1182/blood.2021015325.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyeloid leukemiaEVI1 isoformsSF3B1 mutationsAberrant 3' splice sitesSelf-renewal of hematopoietic stem cellsSplicing factor SF3B1Zinc finger domainExonic splicing enhancerIn-frame insertionCryptic branch pointPathogenesis of myeloid leukemiaPatient-derived cell linesHematopoietic stem cellsRNA-splicingSplicing enhancerSplice siteEpigenomic analysesMutant SF3B1Promoter usageExon 13Leukemic transformationSplice variantsGenomic alterationsUpregulated transcriptsSynthetic introns enable splicing factor mutation-dependent targeting of cancer cells
North K, Benbarche S, Liu B, Pangallo J, Chen S, Stahl M, Bewersdorf J, Stanley R, Erickson C, Cho H, Pineda J, Thomas J, Polaski J, Belleville A, Gabel A, Udy D, Humbert O, Kiem H, Abdel-Wahab O, Bradley R. Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells. Nature Biotechnology 2022, 40: 1103-1113. PMID: 35241838, PMCID: PMC9288984, DOI: 10.1038/s41587-022-01224-2.Peer-Reviewed Original ResearchConceptsBreast cancerExpression of herpes simplex virus thymidine kinaseHerpes simplex virus thymidine kinaseCancer cellsPancreatic cancer cells in vitroWild-type cellsCancer cells in vitroCancer gene therapyTargeting of cancer cellsTumor-specific changesUveal melanoma cellsTreatment in vivoSynthetic intronChange-of-function mutationsCells in vitroUveal melanomaSF3B1 mutationsHSV-tkGene therapyTumor cellsIsogenic wild-type cellsMelanoma cellsRNA splicing factorsCancerHost survivalPhase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes
Zeidan AM, DeAngelo DJ, Palmer J, Seet CS, Tallman MS, Wei X, Raymon H, Sriraman P, Kopytek S, Bewersdorf JP, Burgess MR, Hege K, Stock W. Phase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes. Annals Of Hematology 2022, 101: 557-569. PMID: 34981142, PMCID: PMC9414073, DOI: 10.1007/s00277-021-04734-2.Peer-Reviewed Original ResearchConceptsAnti-drug antibodiesAcute myeloid leukemiaDose-limiting toxicityRefractory acute myeloid leukemiaHigh-risk myelodysplastic syndromeMyelodysplastic syndromeMyeloid leukemiaCommon treatment-emergent adverse eventsTreatment-emergent adverse eventsADA-positive patientsPhase 2 dosePresence/frequencyUnexpected safety findingsPhase 1 studyAnti-CD47 antibodyCD47-SIRPα interactionMacrophage-mediated killingHematological cancer cell linesFebrile neutropeniaMonotherapy activityCancer cell linesPrimary endpointSecondary endpointsAdverse eventsObjective response
2019
Calcium Influx through Plasma-Membrane Nanoruptures Drives Axon Degeneration in a Model of Multiple Sclerosis
Witte M, Schumacher A, Mahler C, Bewersdorf J, Lehmitz J, Scheiter A, Sánchez P, Williams P, Griesbeck O, Naumann R, Misgeld T, Kerschensteiner M. Calcium Influx through Plasma-Membrane Nanoruptures Drives Axon Degeneration in a Model of Multiple Sclerosis. Neuron 2019, 101: 615-624.e5. PMID: 30686733, PMCID: PMC6389591, DOI: 10.1016/j.neuron.2018.12.023.Peer-Reviewed Original ResearchConceptsAxonal lossModel of multiple sclerosisSodium-calcium exchangerCytoplasmic calcium levelsMultiple sclerosis modelMultiple sclerosis patientsCalcium entryCalcium influxCalcium levelsCalcium imagingCalcium accumulationGlutamate excitotoxicityPersistent disabilityAxonal degenerationMultiple sclerosisAxonsPlasma membraneEndoplasmic reticulumCalcium
2018
Mast Cells Are Activated by Streptococcus pneumoniae In Vitro but Dispensable for the Host Defense Against Pneumococcal Central Nervous System Infection In Vivo
Fritscher J, Amberger D, Dyckhoff S, Bewersdorf J, Masouris I, Voelk S, Hammerschmidt S, Schmetzer H, Klein M, Pfister H, Koedel U. Mast Cells Are Activated by Streptococcus pneumoniae In Vitro but Dispensable for the Host Defense Against Pneumococcal Central Nervous System Infection In Vivo. Frontiers In Immunology 2018, 9: 550. PMID: 29616039, PMCID: PMC5867309, DOI: 10.3389/fimmu.2018.00550.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsCell DegranulationCells, CulturedCentral Nervous SystemCromolyn SodiumHumansImmunity, InnateMaleMast CellsMeningitis, PneumococcalMiceMice, Inbred C57BLMice, TransgenicMutationPneumococcal InfectionsProto-Oncogene Proteins c-kitStreptococcus pneumoniaeStreptolysinsConceptsBone marrow-derived mast cellsCentral nervous systemSystemic infection in vivoMast cellsBone-marrow-derived mast cell degranulationMast cell engraftmentMouse bone marrow-derived mast cellsBacterial infectionsMarrow-derived mast cellsCerebrospinal fluidMutant mouse strainsMast cell-deficientExperimental pneumococcal meningitisMast cell stabilizerSystemic bacterial infectionInfection in vivoDisease phenotypeCell deficiencyCSF pleocytosisPneumococcal serotypesC-kitCell engraftmentPneumococcal meningitisMouse strainsNervous system