A5008843306- Cancer, Hypoxia, and Metabolism
- Nanoplatforms for cancer theranostics
- Genomics and Chromatin Dynamics
- MRI in cancer diagnosis
- Hepatocellular Carcinoma Treatment and Prognosis
- Lanthanide and Transition Metal Complexes
- Chromosomal and Genetic Variations
- RNA Research and Splicing
- Cancer, Lipids, and Metabolism
- Angiogenesis and VEGF in Cancer
- Single-cell and spatial transcriptomics
- MicroRNA in disease regulation
- Genetic and Kidney Cyst Diseases
- Eicosanoids and Hypertension Pharmacology
- DNA and Nucleic Acid Chemistry
- RNA regulation and disease
- Cancer Research and Treatments
- Epigenetics and DNA Methylation
- Advanced biosensing and bioanalysis techniques
- Circular RNAs in diseases
- Genetics, Aging, and Longevity in Model Organisms
- Telomeres, Telomerase, and Senescence
- DNA Repair Mechanisms
- Photoreceptor and optogenetics research
- Retinal Development and Disorders
Universitätsmedizin Göttingen
2019-2024
University of Cologne
2018-2023
University of Göttingen
2019-2023
University Hospital Cologne
2023
University of Belgrade
2016
Physiological homeostasis becomes compromised during ageing, as a result of impairment cellular processes, including transcription and RNA splicing1-4. However, the molecular mechanisms leading to loss transcriptional fidelity are so far elusive, ways preventing it. Here we profiled analysed genome-wide, ageing-related changes in processes across different organisms: nematodes, fruitflies, mice, rats humans. The average elongation speed (RNA polymerase II speed) increased with age all five...
Following exit from mitosis, RNA Pol II is required for reestablishing 3D genome folding by loading cohesin complexes onto DNA.
Cohesin is a ring-shaped multiprotein complex that crucial for 3D genome organization and transcriptional regulation during differentiation development. It also confers sister chromatid cohesion facilitates DNA damage repair. Besides its core subunits SMC3, SMC1A, RAD21, cohesin in somatic cells contains one of two orthologous STAG subunits, STAG1 or STAG2. How these variable affect the function still unclear. STAG1- STAG2-cohesin were initially proposed to organize at telomeres centromeres,...
Glioblastoma multiforme (GBM) possesses glioma stem cells (GSCs) that promote self-renewal, tumor propagation, and relapse. Understanding the mechanisms of GSCs self-renewal can offer targeted therapeutic interventions. However, insufficient knowledge GSCs' fundamental biology is a significant bottleneck hindering these efforts. Here, we show patient-derived recruit elevated levels proteins ensure temporal cilium disassembly, leading to suppressed ciliogenesis. Depleting cilia disassembly...
ABSTRACT The 10x Genomics Gene Expression Flex protocol allows profiling of fixed or frozen material, greatly simplifying the logistics sample collection, storage and transfer prior to single -cell sequencing. method makes single-cell transcriptomics possible for existing fresh-frozen FFPE tissue samples, but also facilitates sampling process, allowing instant preservation samples. technology relies on species-specific probes available human mouse. Nevertheless, processing patient-derived...
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A distinct combination of transcription factors elicits the acquisition a specific fate and initiation differentiation program. Multiciliated cells (MCCs) are specialized type epithelial that possess dozens motile cilia on their apical surface. Defects in function have been associated with ciliopathies affect many organs, including brain airway epithelium. Here we show geminin coiled-coil domain-containing protein 1 GemC1 (also known as Lynkeas) regulates transcriptional activation p73,...
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...
Cellular senescence is acknowledged as a key contributor to organismal ageing and late-life disease. Though popular, the study of in vitro can be complicated by prolonged asynchronous timing cells committing it its paracrine effects. To address these issues, we repurposed small molecule inhibitor, inflachromene (ICM), induce human primary cells. Within 6 days treatment with ICM, hallmarks, including nuclear eviction HMGB1 -B2, are uniformly induced across IMR90 cell populations. By...
It is widely accepted that adenosine triphosphate (ATP) acts as a universal danger‐associated molecular pattern with several known mechanisms for immune cell activation. In the central nervous system, ATP activates microglia and astrocytes induces neuroinflammatory response. The aim of present study was to describe responses isolated increasing concentrations (5 µM 1 mM), which were intended mimic graded intensity extracellular stimulus. results show activation response in terms...
Abstract A hallmark of senescence is the acquisition an enhanced secretome comprising inflammatory mediators and tissue remodelling agents – senescence‐associated secretory phenotype (SASP). Through SASP, senescent cells are hypothesised to contribute both ageing pathologies associated with age. Whilst soluble factors have been most widely investigated components there growing evidence that small extracellular vesicles (EVs) comprise functionally important constituents. Thus, dissecting...
Abstract Treatment of patients with locally advanced rectal cancer (RC) is based on neoadjuvant chemoradiotherapy followed by surgery. In order to reduce the development therapy resistance, it necessary further improve previous treatment approaches. Recent in vivo experimental studies suggested that reduction tumor hypoxia vessel normalization (TVN), through inhibition glycolytic activator PFKFB3, could significantly response therapy. We have evaluated vitro and effects PFKFB3 inhibitor...
Abstract Cohesin is a ring-shaped multiprotein complex that crucial for 3D genome organization and transcriptional regulation during differentiation development. It also confers sister chromatid cohesion facilitates DNA damage repair. Besides its core subunits SMC3, SMC1A RAD21, cohesin contains in somatic cells one of two orthologous STAG subunits, SA1 or SA2. How these variable affect the function still unclear. SA1- SA2-cohesin were initially proposed to organize at telomeres centromeres,...
SUMMARY Mammalian chromosomes are three-dimensional entities shaped by converging and opposing forces. Mitotic cell division induces drastic chromosome condensation, but following reentry into the G1 cycle phase, condensed unwind to reestablish interphase organization. Here, we use a line allowing auxin-mediated degradation of RNA polymerase II test its role in this transition. In situ Hi-C showed that RNAPII is required for compartment loop formation mitosis. RNAPs often counteract...