A5066475986- Pluripotent Stem Cells Research
- Developmental Biology and Gene Regulation
- Animal testing and alternatives
- TGF-β signaling in diseases
- 3D Printing in Biomedical Research
- Effects and risks of endocrine disrupting chemicals
- Carcinogens and Genotoxicity Assessment
- Congenital heart defects research
- Cell Adhesion Molecules Research
- Kruppel-like factors research
- bioluminescence and chemiluminescence research
- Computational Drug Discovery Methods
- NF-κB Signaling Pathways
- Protein Kinase Regulation and GTPase Signaling
- CRISPR and Genetic Engineering
- Glycosylation and Glycoproteins Research
- Connective Tissue Growth Factor Research
- Wnt/β-catenin signaling in development and cancer
- Anesthesia and Neurotoxicity Research
- Health, Environment, Cognitive Aging
- Renal and related cancers
- Circadian rhythm and melatonin
- Biomedical Ethics and Regulation
- Light effects on plants
- Genomics and Chromatin Dynamics
Federal Institute for Risk Assessment
2016-2025
Max Planck Institute of Immunobiology and Epigenetics
2004-2014
Max Planck Society
2004-2006
In-Q-Tel
2006
University of California, Los Angeles
2000-2003
Howard Hughes Medical Institute
2001-2003
Medizinische Hochschule Hannover
1995-2001
Northeastern University
1994
ABSTRACT In Xenopus, mesoderm induction by endoderm at the blastula stage is well documented, but molecular nature of endogenous inductive signals remains unknown. The carboxy-terminal fragment Cerberus, designated Cer-S, provides a specific secreted antagonist mesoderm-inducing Xenopus Nodal-Related (Xnr) factors. Cer-S does not inhibit signalling other inducers such as Activin, Derrière, Vg1 and BMP4, nor neural inducer Xnr3. present study we show that blocks both dorsal ventral in...
The murine neutrophil elastase (NE) gene is expressed specifically in immature myeloid cells. A 91-bp NE promoter region contains three cis elements which are conserved evolutionarily and essential for activation of the differentiating 32D cl3 These bound c-Myb (at -49), C/EBPalpha -57), PU.1 -82). In NIH 3T3 cells, was activated by c-Myb, C/EBPalpha, PU.1, via their respective binding sites. Cooperative seen any combination including all together, again DNA-binding CV-1 but not cooperation...
Dorsoventral patterning is regulated by a system of interacting secreted proteins involving BMP, Chordin, Xolloid and Twisted gastrulation (Tsg). We have analyzed the molecular mechanism which Tsg regulates BMP signaling. Overexpression mRNA in Xenopus embryos has ventralizing effects similar to Xolloid, metalloprotease that cleaves Chordin. In dorsalized LiCl treatment, microinjection or restores formation trunk-tail structures, indicating an increase Microinjection leads degradation...
A key challenge of mixture toxicity testing is that a multitude substances with even more combinations need to be tested in broad dose range. Consequently rodent bioassays, the current gold standard testing, hardly feasible. High-throughput compatible cell culture systems, however, suffer from limitations respect toxicokinetics, tissue interactions, and compensatory mechanisms. Therefore, simple organisms like nematode Caenorhabditis elegans, combining relevant advantages complex vivo fast...
Humans are involuntarily exposed to hundreds of chemicals that either contaminate our environment and food or added intentionally daily products. These complex mixtures may pose a risk human health. One the goals European Union’s Green Deal zero-pollution ambition for toxic-free is tackle existent gaps in chemical mixture assessment by providing scientific grounds support implementation adequate regulatory measures within EU. We suggest dealing with this challenge by: (1) characterising...
Phosphorylation of c-Myb has been implicated in the regulation binding to DNA. We show that murine is phosphorylated at Ser-11 and -12 vivo these sites can be vitro by casein kinase II (CKII), analogous chicken c-Myb. An efficient method study DNA properties full-length Myb mutants under nondenaturing conditions was developed. It found a mutant which were replaced with Ala (Myb Ala-11/12), wild-type c-Myb, Asp-11/12 bound A site mim-1 promoter decreasing affinities. In agreement this...
Accurate simulation of different cell type interactions is crucial for physiological and precisein vitrodrug testing. Human tissue-resident macrophages are critical modulating disease conditions drug-induced injuries in various tissues; however, their limited availability has hindered use inin vitromodeling. Therefore, this study aimed to create macrophage-containing organoid co-culture models by directly incorporating human-induced pluripotent stem (hiPSC)-derived pre-macrophages into...
Abstract The potential risk of chemicals to the human eye is assessed by adopted test guidelines (TGs) for regulatory purposes ensure consumer safety. Over past decade, Organization Economic Co-operation and Development (OECD) has approved new approach methodologies (NAMs) predict chemical damage. However, existing NAMs remain associated with limitations: First, no full replacement in vivo Draize due limited predictability severe/mild damage was reached. Second, do not allow reliable...
The determination of the vertebrate dorsoventral body axis is regulated in extracellular space by a system interacting secreted molecules consisting BMP, Chordin, Tolloid and Twisted Gastrulation (Tsg). Tsg BMP-binding protein that forms ternary complexes with BMP Chordin. We investigated function embryonic patterning generating point mutations its two conserved cysteine-rich domains. Surprisingly, proteins N-terminal domain were unable to bind yet ventralized embryo very effectively,...
In biomedical research, the past two decades have seen advent of in vitro model systems based on stem cells, humanized cell lines, and engineered organotypic tissues, as well numerous cellular assays primarily established tumor-derived lines their genetically modified derivatives.There are high hopes that these might replace need for animal testing regulatory toxicology. However, despite increasing pressure recent years to reduce testing, regulators still reluctant adopt approaches a large...
Studying chemical disturbances during neural differentiation of murine embryonic stem cells (mESCs) has been established as an alternative in vitro testing approach for the identification developmental neurotoxicants. miRNAs represent a class small non-coding RNA molecules involved regulation development and ESC specification. Thus, mESCs allows investigating role chemical-mediated toxicity. We analyzed changes miRNome transcriptome exposed to neurotoxicant sodium valproate (VPA). A total...