A5017245275- Pluripotent Stem Cells Research
- 14-3-3 protein interactions
- Anesthesia and Neurotoxicity Research
- Neuroscience and Neural Engineering
- 3D Printing in Biomedical Research
- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Neurogenesis and neuroplasticity mechanisms
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- MicroRNA in disease regulation
- Animal testing and alternatives
- Estrogen and related hormone effects
- Neonatal Respiratory Health Research
- Eicosanoids and Hypertension Pharmacology
- Effects and risks of endocrine disrupting chemicals
- Adipose Tissue and Metabolism
- Cancer, Stress, Anesthesia, and Immune Response
- Microtubule and mitosis dynamics
- Scientific Research and Philosophical Inquiry
- Nerve injury and regeneration
- Wnt/β-catenin signaling in development and cancer
- Medicinal Plants and Neuroprotection
- Discourse Analysis and Cultural Communication
- Advanced biosensing and bioanalysis techniques
Leibniz Institute of Environmental Medicine
2020-2025
Heinrich Heine University Düsseldorf
2015-2021
Düsseldorf University Hospital
2015-2021
University of Bonn
2016
Abstract Cancer cells upregulate anabolic processes to maintain high rates of cellular turnover. Limiting the supply macromolecular precursors by targeting enzymes involved in biosynthesis is a promising strategy cancer therapy. Several tumors excessively metabolize glutamine generate for nonessential amino acids, nucleotides, and lipids, process called glutaminolysis. Here we show that pharmacological inhibition glutaminase (GLS) eradicates glioblastoma stem-like (GSCs), small cell...
The mannose receptor (MR) is an endocytic involved in serum homeostasis and antigen presentation. Here, we identify the MR as a direct regulator of CD8(+) T-cell activity. We demonstrate that expression on dendritic cells (DCs) impaired cytotoxicity vitro vivo. This regulatory effect was mediated by interaction with CD45 T cell, inhibiting its phosphatase activity, which resulted up-regulation cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4) induction tolerance. Inhibition prevented...
Wingless (Wnt) signaling is an important pathway in gliomagenesis and the growth of stem-like glioma cells. Using immunohistochemistry to assess translocation β-catenin protein, we identified intranuclear staining suggesting Wnt activation 8 43 surgical samples (19%) from adult patients with glioblastoma 9 30 (30%) pediatric glioblastoma. activity, evidenced by nuclear our cohort high expression its target AXIN2 (axis inhibitor protein 2) published datasets, was associated shorter patient...
Glioblastoma is the most aggressive type of glioma. The Wingless (Wnt) signaling pathway has been shown to promote stem cell properties and resistance radio- chemotherapy in glioblastoma. Here, we demonstrate that pharmacological Wnt inhibition using porcupine inhibitor LGK974 acts synergistically with temozolomide (TMZ), chemotherapeutic drug currently used as standard treatment for glioblastoma, suppress vitro growth glioma cells. Synergistic was independent O6-alkylguanine DNA...
Abstract Due to their neurodevelopmental toxicity, flame retardants (FRs) like polybrominated diphenyl ethers are banned from the market and replaced by alternative FRs, organophosphorus that have mostly unknown toxicological profiles. To study we evaluated hazard of several FRs including phased-out FRs: 2,2′,4,4′-tetrabromodiphenylether (BDE-47), 2,2′,4,4′,5-pentabromodiphenylether (BDE-99), tetrabromobisphenol A, triphenyl phosphate, tris(2-butoxyethyl) phosphate its metabolite...
There is a call for paradigm shift in developmental neurotoxicity (DNT) evaluation, which demands the implementation of faster, more cost-efficient, and human-relevant test systems than current vivo guideline studies. Under umbrella Organisation Economic Co-operation Development (OECD), guidance document currently being prepared that instructs on regulatory use DNT vitro battery (DNT IVB) fit-for-purpose applications. One crucial issue OECD application methods validation, new approach (NAMs)...
On occasion of the DNT5 meeting in Konstanz, Germany (April-2024), participants brainstormed on future challenges concerning a regulatory implementation developmental neurotoxicity (DNT) vitro test battery (DNT-IVB). The five discussion topics below outline some key issues, opportunities and research directions for next several years: (1) How to contextualize DNT hazard with information potential maternal toxicity or other domains (non-DNT)? Several approaches how use cytotoxicity data from...
Despite growing awareness of endocrine disrupting chemicals (EDCs), knowledge gaps remain regarding their effects on human brain development. EDC risk assessment focuses primarily EATS modalities (estrogens, androgens, thyroid hormones, and steroidogenesis), overlooking the broader range hormone receptors expressed in developing brain. This limits evaluation for potential to cause disruption-mediated developmental neurotoxicity (ED-DNT). The Neurosphere Assay, an vitro test method (DNT)...
Notch signaling can promote tumorigenesis in the nervous system and plays important roles stem-like cancer cells. However, little is known about how inhibition might alter tumor metabolism, particularly lesions arising brain. The gamma-secretase inhibitor MRK003 was used to treat glioblastoma neurospheres, they were subdivided into sensitive insensitive groups terms of canonical target response. Global metabolomes then examined using proton magnetic resonance spectroscopy, changes...
Glioblastoma is the most common and lethal primary brain cancer. CBF1 (also known as Recombination signal Binding Protein for immunoglobulin kappa J, RBPJ) cardinal transcriptional regulator of Notch signalling network has been shown to promote cancer stem-like cells (CSCs) in glioblastoma. Recent studies suggest that some malignant properties CSCs are mediated through activation pro-invasive programme epithelial-to-mesenchymal transition (EMT). Little whether involved EMT-like phenotype...
Glioblastoma (GBM) is the most malignant brain tumor with very limited therapeutic options. Standard multimodal treatments, including surgical resection and combined radio-chemotherapy do not target aggressive subtype of glioma cells, stem cells (BTSCs). BTSCs are thought to be responsible for initiation, progression, relapse. Furthermore, they have been associated expression mesenchymal features as a result epithelial-mesenchymal transition (EMT) thereby inducing dissemination chemo...
The currently accepted methods for neurotoxicity (NT) testing rely on animal studies. However, high costs and low throughput hinder their application large numbers of chemicals. To overcome these limitations, in vitro are being developed based human-induced pluripotent stem cells (hiPSC) that allow higher at lower costs. We applied six different protocols to generate 3D BrainSphere models acute NT evaluation. These include three media 2D neural induction two subsequent differentiation...
Myelinating oligodendrocytes (OLs) establish saltatory nerve conduction during white matter development. Thus, interference with oligodendrogenesis leads to an adverse outcome on brain performance in the child due aberrant myelination. An intertwined network of hormonal, transcriptional and biosynthetic processes regulates OL development, thereby simultaneously creating various routes for environmental toxicants. The flame retardant tetrabromobisphenol A (TBBPA) is debated as endocrine...
Glioblastoma (GBM) is the most aggressive malignant primary brain tumour in adulthood. Despite strong research efforts current treatment options have a limited impact on glioma stem-like cells (GSCs) which contribute to GBM formation, progression and chemoresistance. Invasive growth of GSCs part associated with epithelial–mesenchymal-like transition (EMT), mechanism CD73 several cancers. Here, we show that regulates EMT activator SNAIL1 further investigate role enzymatic non-enzymatic...
Abstract For 3D neural cultures durable hydrogels are required, which persist over a long differentiation period and thus enable the maturation of neuronal networks (NN). Here, models based on human induced pluripotent stem cell‐derived progenitor cells that embedded in either pure alginate or functionalized with extracellular matrix protein laminin 111 (L111) established. This study analyzes material characteristics such as porosity, L111 distribution shear viscosity, cell compatibility by...
Abstract Adverse outcome pathways (AOPs) are organized sequences of key events (KEs) that triggered by a xenobiotic-induced molecular initiating event (MIE) and summit in an adverse (AO) relevant to human or ecological health. The AOP framework causally connects toxicological mechanistic information with apical endpoints for application regulatory sciences. AOPs very useful link endophenotypic, cellular vitro health effects vivo. In the field developmental neurotoxicity (DNT), such can be...
Abstract Cockayne Syndrome B (CSB) is a hereditary multiorgan syndrome which—through largely unknown mechanisms—can affect the brain where it clinically presents with microcephaly, intellectual disability and demyelination. Using human induced pluripotent stem cell (hiPSC)-derived neural 3D models generated from CSB patient-derived isogenic control lines, we here provide explanations for these three major neuropathological phenotypes. In our models, deficiency associated (i) impaired...
Cancer stem-like cells mediate tumor initiation, progression, and therapy resistance; however, their identification selective eradication remain challenging. Herein, we analyze the metabolic dependencies of glioblastoma (GSCs) with high-resolution proton nuclear magnetic resonance (1H-NMR) spectroscopy. We stratify our in vitro GSC models into two subtypes primarily based on relative amount glutamine relationship to glutamate (Gln/Glu). Gln/GluHigh GSCs were found be resistant deprivation,...
ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Kahlert U, Koch K, Suwala A, et al. The effect of neurosphere culture conditions on the cellular metabolism glioma cells. Folia Neuropathologica. 2015;53(3):219-225. doi:10.5114/fn.2015.54422. APA Kahlert, U., Koch, K., Suwala, A., Hartmann, R., Cheng, M., & Maciaczyk, D. (2015). Neuropathologica, 53(3), 219-225. https://doi.org/10.5114/fn.2015.54422 Chicago Ulf Dietrich, Katharina Abigail Kora Rudolf Menglin...