A5086037421- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Immune Response and Inflammation
- Takotsubo Cardiomyopathy and Associated Phenomena
- Chemotherapy-induced cardiotoxicity and mitigation
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Advanced Glycation End Products research
- Immune cells in cancer
- Acute Myeloid Leukemia Research
- Chromosomal and Genetic Variations
- Nitric Oxide and Endothelin Effects
- Telomeres, Telomerase, and Senescence
- Cancer-related cognitive impairment studies
- Advanced biosensing and bioanalysis techniques
- CRISPR and Genetic Engineering
- Cell Adhesion Molecules Research
- Single-cell and spatial transcriptomics
- Cancer-related molecular mechanisms research
- RNA Interference and Gene Delivery
University of Cologne
2018-2024
University Hospital Cologne
2021-2024
Universitätsmedizin Göttingen
2018
Johannes Gutenberg University Mainz
2016-2017
University Medical Center of the Johannes Gutenberg University Mainz
2017
RNA-binding proteins (RBPs) are central for gene expression by controlling the RNA fate from birth to decay. Various disorders arising perturbations of RNA–protein interactions document their critical function. However, deciphering function is complex, limiting general functional elucidation this growing class and contribution (patho)physiology. Here, we present sCLIP, a simplified robust platform genome-wide interrogation interactomes based on crosslinking-immunoprecipitation...
Cardiotoxicity is a major complication of anthracycline therapy that negatively impacts prognosis. Effective pharmacotherapies for prevention anthracycline-induced cardiomyopathy (AICM) are currently lacking. Increased plasma levels the neutrophil-derived enzyme myeloperoxidase (MPO) predict occurrence AICM in humans. We hypothesized MPO release causally contributes to AICM. Mice intravenously injected with doxorubicin (DOX) exhibited higher neutrophil counts and circulation cardiac tissue...
Abstract Members of the chromodomain-helicase-DNA binding (CHD) protein family are chromatin remodelers implicated in human pathologies, with CHD6 being one its least studied members. We discovered a de novo missense mutation patient clinically presenting rare Hallermann-Streiff syndrome (HSS). used genome editing to generate isogenic iPSC lines and model HSS relevant cell types. By combining genomics functional vivo vitro assays, we show that binds cohort autophagy stress response genes...
Myeloperoxidase (MPO) is an enzyme that functions in host defense. MPO released into the vascular lumen by neutrophils during inflammation and may adhere subsequently penetrate endothelial cells (ECs) coating walls. We show enters nucleus of ECs binds chromatin independently its enzymatic activity. drives decondensation at binding sites enhances condensation neighboring regions. It loci relevant for endothelial-to-mesenchymal transition (EndMT) affects migratory potential ECs. Finally,...
ABSTRACT Senescence —the endpoint of replicative lifespan for normal cells— is established via a complex sequence molecular events. One such event the dramatic reorganization CTCF into senescence-induced clusters (SICCs). However, determinants, genomic consequences, and functional purpose SICCs remained unknown. Here, we combine assays, super-resolution imaging, 3D genomics with computational modelling to dissect SICC emergence. We establish that competition between CTCF-bound non-bound loci...
Abstract Spatial organization and gene expression of mammalian chromosomes are maintained regulated in conjunction with cell cycle progression. This is however disturbed once cells enter senescence the highly abundant HMGB1 protein depleted from senescent nuclei to act as an extracellular proinflammatory stimulus. Despite its physiological importance, we know little about positioning on chromatin or roles nucleus. To address this, mapped binding genome-wide different primary using a tailored...
ABSTRACT Members of the chromodomain-helicase-DNA binding (CHD) protein family are chromatin remodelers critically implicated in human pathologies, with CHD6 being one its least studied members. Here, we discovered a de novo missense mutation patient clinically presenting rare Hallermann-Streiff syndrome (HSS). We used genome editing to generate isogenic iPSC lines and model HSS relevant cell types. show that binds cohort autophagy stress response genes across The HSS-mutation affects...
ABSTRACT Myeloperoxidase (MPO) is an enzyme that functions in host defence by catalysing the formation of reactive oxygen intermediates. Synthesized majorly myeloid progenitor cell types and neutrophils, MPO released into vascular lumen during inflammation, where it may adhere subsequently enter endothelial cells coating walls. Here, we show actually enters nucleus these binds chromatin independently its enzymatic activity to cause changes structure. At binding sites, drives decondensation,...
Abstract Cardiotoxicity is a major complication of anthracycline therapy that negatively impacts prognosis. Effective pharmacotherapies for prevention anthracycline-induced cardiomyopathy (AICM) are currently lacking. Increased plasma levels the neutrophil-derived enzyme myeloperoxidase (MPO) predict occurrence AICM in humans. We hypothesized MPO release causally contributes to AICM. Mice intravenously injected with Doxorubicin (DOX) exhibited higher neutrophil counts and circulation cardiac...