- Neurogenesis and neuroplasticity mechanisms
- Nerve injury and regeneration
- Pluripotent Stem Cells Research
- Congenital heart defects research
- Tissue Engineering and Regenerative Medicine
- Alzheimer's disease research and treatments
- Stress Responses and Cortisol
- Sleep and Wakefulness Research
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Mesenchymal stem cell research
- Neurogenetic and Muscular Disorders Research
- Cannabis and Cannabinoid Research
- Genetics and Neurodevelopmental Disorders
- Cardiomyopathy and Myosin Studies
- Cancer-related gene regulation
- Diet and metabolism studies
- Receptor Mechanisms and Signaling
- Amyotrophic Lateral Sclerosis Research
- Spinal Cord Injury Research
- Genetic Neurodegenerative Diseases
- Cellular transport and secretion
- Biochemical Acid Research Studies
- Cholinesterase and Neurodegenerative Diseases
- Anesthesia and Neurotoxicity Research
University Medical Center of the Johannes Gutenberg University Mainz
2013-2022
Johannes Gutenberg University Mainz
2013-2022
Délégation Paris 5
2021
Inserm
2007-2021
Université Paris Cité
2014-2021
Descartes (Belgium)
2021
UNSW Sydney
2015
Genopole (France)
2014
Institut des Cellules Souches pour le Traitement et l'Étude des Maladies Monogéniques
2007
Osnabrück University
2004-2007
Direct reprogramming of somatic cells into induced pluripotent stem (iPSCs) provides a unique opportunity to derive patient-specific with potential applications in tissue replacement therapies and without the ethical concerns human embryonic (hESCs). However, cellular senescence, which contributes aging restricted longevity, has been described as barrier derivation iPSCs. Here we demonstrate, using an optimized protocol, that senescence is not limit age-related physiology reversible. Thus,...
Human embryonic stem (HES) cells can give rise to cardiomyocytes in vitro. However, whether undifferentiated HES also feature a myocardial regenerative capacity after vivo engraftment has not been established yet. We compared two cell lines (HUES-1 and I6) that were specified toward cardiac lineage by exposure bone morphogenetic protein-2 (BMP2) SU5402, fibroblast growth factor receptor inhibitor. Real-time polymerase chain reaction (PCR) revealed the cardiogenic inductive turned on...
LMNA mutations in patients are responsible for a dilated cardiomyopathy. Molecular mechanisms underlying the origin and development of pathology unknown. Herein, using mouse pluripotent embryonic stem cells (ESCs) model both harboring p.H222P Lmna mutation, we found early defects cardiac differentiation mutated ESCs dilatation hearts at E13.5, pointing to developmental disease. Using ESCs, demonstrated that LmnaH222P/+ was impaired mesodermal stage. Expression Mesp1, cardiogenic gene...
The neurotrophin brain-derived neurotrophic factor (BDNF) stimulates adult neurogenesis, but also influences structural plasticity and function of serotonergic neurons. Both, BDNF/TrkB signaling the system modulate behavioral responses to stress can lead pathological states when dysregulated. two systems have been shown mediate therapeutic effect antidepressant drugs regulate hippocampal neurogenesis. To elucidate interplay both at cellular levels, we generated a transgenic mouse line that...
Neural stem cells (NSCs) in the adult mouse hippocampus occur a specific neurogenic niche, where multitude of extracellular signaling molecules converges to regulate NSC proliferation as well fate and functional integration. However, underlying mechanisms how NSCs react extrinsic signals convert them intracellular responses still remains elusive. contain endocannabinoid system, including cannabinoid type-1 receptor (CB1). To decipher whether CB1 regulates neurogenesis directly or indirectly...
Mammalian neurofilaments (NFs) are modified by post-translational modifications that thought to regulate NF assembly and organization. Whereas phosphorylation has been intensely studied, the role of another common modification, attachment O-linked N-acetylglucosamine (GlcNAc) individual serine threonine residues, is hardly understood. We generated a novel monoclonal antibody specifically recognizes an O-glycosylated epitope in tail domain NF-M allows determination glycosylation state at this...
Postsynaptically generated 2-arachidonoylglycerol activates the presynaptic cannabinoid type-1 receptor, which is involved in synaptic plasticity at both glutamatergic and GABAergic synapses. However, differential function of signaling vs synapses context animal behavior has not been investigated yet.Here, we analyzed role selectively hippocampal neurons. Monoacylglycerol lipase, primary degrading enzyme 2-arachidonoylglycerol, expressed sites excitatory inhibitory By adeno-associated...
Abstract Alzheimer’s disease (AD) is characterized by massive neuron loss in distinct brain regions, extracellular accumulations of the amyloid precursor protein‐fragment amyloid‐β (Aβ) and intracellular tau fibrils containing hyperphosphorylated tau. Experimental evidence suggests a relation between presenilin (PS) mutations, Aβ formation, phosphorylation triggering cell death; however, how PS affect tau‐dependent degeneration unknown. Using herpes simplex virus 1‐mediated gene‐transfer...
Huntington's disease (HD) is characterized by fatal motoric failures induced loss of striatal medium spiny neurons. Neuronal cell death has been linked to impaired expression and axonal transport the neurotrophin BDNF (brain-derived neurotrophic factor). By transplanting embryonic stem cell-derived neural progenitors overexpressing BDNF, we combined replacement supply as a potential HD therapy approach. Transplantation purified was analyzed in quinolinic acid (QA) chemical two genetic mouse...
The neurotrophin brain derived neurotrophic factor (BDNF) is an important growth in the CNS. Deficits transport of this secretory protein could underlie neurodegenerative diseases. Investigation disease-related changes BDNF might provide insights into cellular mechanism underlying, for example, Alzheimer’s disease (AD). To analyze role AD, live cell imaging fluorescently labeled was performed hippocampal neurons different AD model systems. and APP colocalized with low incidence vesicular...
Neural stem cells for the treatment of spinal cord injury (SCI) are particular interest future therapeutic use. However, until now, cell therapies often limited due to inhibitory environment following injury. Therefore, in this study, we aimed at testing a combinatorial approach with BDNF (brain-derived neurotrophic factor) overexpressing early neural progenitors derived from mouse embryonic cells. is neurotrophin, which both facilitates differentiation and favors regeneration damaged...
Brain-derived neurotrophic factor (BDNF) is known to be a crucial regulator of neuronal survival and synaptic plasticity in the mammalian brain. Furthermore, BDNF positively influences differentiation embryonic neural precursors as well stem cells from adult neurogenic niches. To study impact cell-released on (ESCs), which represent an attractive source for cell transplantation studies, we have generated BDNF-GFP overexpressing mouse ESC clones by knock-in technology. After vitro, observed...
Human embryonic stem (HUES) cells are derived from early individual embryos with unique genetic printing. However, how their epigenetic status might affect potential to differentiate toward specific lineages remains a puzzling question. Using chromatin immunoprecipitation (ChIP)–polymerase chain reaction and ChIP-on-chip, the of bivalent domains on gene promoters (ie, histone 3 lysine 4 27 trimethylation) was monitored for both undifferentiated bone morphogenetic protein 2 (BMP2)-induced...
Brain-derived neurotrophic factor (BDNF) is known to be a crucial regulator of neuronal survival and synaptic plasticity in the mammalian brain. Furthermore, BDNF positively influences differentiation embryonic neural precursors, as well that stem cells from adult neurogenic niches. To study impact cell-released on (ESCs), which represent an attractive source for cell transplantation studies, we have generated mouse ESC clones overexpressing BDNF-GFP by use knock-in technology. After vitro,...
Specific gene transcription is a key biological process that underlies cell fate decision during embryonic development. The mediated by factors which bind genomic regulatory regions including enhancers and promoters of cardiac constitutive genes. DNA wrapped around histones are subjected to chemical modifications. Modifications further lead repressed, activated or poised transcription, thus bringing another level fine tuning regulation transcription. Embryonic Stem cells (ES cells)...
Specific gene transcription is a key biological process that underlies cell fate decision during embryonic development. The mediated by factors which bind genomic regulatory regions including enhancers and promoters of cardiac constitutive genes. DNA wrapped around histones are subjected to chemical modifications. Modifications further lead repressed, activated or poised transcription, thus bringing another level fine tuning regulation transcription. Embryonic Stem cells (ES cells)...