0000000000189461

AUTHOR

Johannes Beckers

showing 4 related works from this author

Murine tissue factor disulfide mutation causes a bleeding phenotype with sex specific organ pathology and lethality.

2019

Tissue factor is highly expressed in sub-endothelial tissue. The extracellular allosteric disulfide bond Cys186-Cys209 of human tissue factor shows high evolutionary conservation and in vitro evidence suggests that it significantly contributes to tissue factor procoagulant activity. To investigate the role of this allosteric disulfide bond in vivo, we generated a C213G mutant tissue factor mouse by replacing Cys213 of the corresponding disulfide Cys190-Cys213 in murine tissue factor. A bleeding phenotype was prominent in homozygous C213G tissue factor mice. Pre-natal lethality of 1/3rd of homozygous offspring was observed between E9.5 and E14.5 associated with placental hemorrhages. After b…

Malemedicine.medical_specialtyOffspring610 Medicine & healthHemorrhage030204 cardiovascular system & hematologyBiologymedicine.disease_causeArticleThromboplastin11459 Center for Molecular Cardiology03 medical and health sciencesTissue factorArterial Thrombosis; Blood Coagulation and Fibrinolysis; Disorders of Coagulation and FibrinolysisMice0302 clinical medicineIn vivoPregnancyInternal medicinemedicineExtracellularAnimalsDisulfidesMutationHematologyPhenotypeIn vitroEndocrinologyPhenotype10036 Medical Clinic10076 Center for Integrative Human PhysiologyHemostasisMutation10209 Clinic for CardiologyFemale030215 immunologyHaematologica
researchProduct

Transcriptional Mechanisms of Proneural Factors and REST in Regulating Neuronal Reprogramming of Astrocytes

2015

Summary Direct lineage reprogramming induces dramatic shifts in cellular identity, employing poorly understood mechanisms. Recently, we demonstrated that expression of Neurog2 or Ascl1 in postnatal mouse astrocytes generates glutamatergic or GABAergic neurons. Here, we take advantage of this model to study dynamics of neuronal cell fate acquisition at the transcriptional level. We found that Neurog2 and Ascl1 rapidly elicited distinct neurogenic programs with only a small subset of shared target genes. Within this subset, only NeuroD4 could by itself induce neuronal reprogramming in both mouse and human astrocytes, while co-expression with Insm1 was required for glutamatergic maturation. Cu…

Transcription GeneticRepressorNerve Tissue ProteinsCell fate determinationBiologyDNA-binding proteinArticleMiceGlutamatergicBasic Helix-Loop-Helix Transcription FactorsGeneticsAnimalsHumansPromoter Regions GeneticTranscription factorCells CulturedNeuronsCell BiologyCellular ReprogrammingMolecular biologyCell biologyDNA-Binding ProteinsRepressor ProteinsASCL1Astrocytesembryonic structuresMolecular MedicineGABAergicReprogrammingTranscription FactorsCell Stem Cell
researchProduct

Identification and validation of novel ERBB2 (HER2, NEU) targets including genes involved in angiogenesis.

2005

V-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2; synonyms HER2, NEU) encodes a transmembrane glycoprotein with tyrosine kinase-specific activity that acts as a major switch in different signal-transduction processes. ERBB2 amplification and overexpression have been found in a number of human cancers, including breast, ovary and kidney carcinoma. Our aim was to detect ERBB2-regulated target genes that contribute to its tumorigenic effect on a genomewide scale. The differential gene expression profile of ERBB2-transfected and wild-type mouse fibroblasts was monitored employing DNA microarrays. Regulated expression of selected genes was verified by RT-PCR and validated by West…

Cancer ResearchReceptor ErbB-2Blotting WesternViral OncogeneDown-RegulationComputational biologyBiologymedicine.disease_causeTransfectionGenomeMiceGene expressionmedicineAnimalsHumansskin and connective tissue diseasesGeneDNA PrimersGlycoproteinsOligonucleotide Array Sequence AnalysisGeneticsRegulation of gene expressionGenomeNeovascularization PathologicReverse Transcriptase Polymerase Chain ReactionFibroblastsGenes erbB-2Up-RegulationGene expression profilingGene Expression Regulation NeoplasticCell Transformation NeoplasticOncologyNIH 3T3 CellsDNA microarrayCarcinogenesisSignal TransductionInternational journal of cancer
researchProduct

Identification and Successful Negotiation of a Metabolic Checkpoint in Direct Neuronal Reprogramming

2016

Despite the widespread interest in direct neuronal reprogramming, the mechanisms underpinning fate conversion remain largely unknown. Our study revealed a critical time point after which cells either successfully convert into neurons or succumb to cell death. Co-transduction with Bcl-2 greatly improved negotiation of this critical point by faster neuronal differentiation. Surprisingly, mutants with reduced or no affinity for Bax demonstrated that Bcl-2 exerts this effect by an apoptosis-independent mechanism. Consistent with a caspase-independent role, ferroptosis inhibitors potently increased neuronal reprogramming by inhibiting lipid peroxidation occurring during fate conversion. Genome-w…

0301 basic medicineGeneticsProgrammed cell deathCell typeCellular Reprogramming TechniquesMutantCell BiologyBiologyIn vitroCell biology03 medical and health sciencesTransduction (genetics)030104 developmental biologyIn vivoGeneticsMolecular MedicineReprogrammingCell Stem Cell
researchProduct