A5002488831- Alzheimer's disease research and treatments
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Zebrafish Biomedical Research Applications
- Neurological Disease Mechanisms and Treatments
- RNA Research and Splicing
- Parkinson's Disease Mechanisms and Treatments
- Single-cell and spatial transcriptomics
- Amyotrophic Lateral Sclerosis Research
- Mitochondrial Function and Pathology
- Genomics and Chromatin Dynamics
- Genetics, Aging, and Longevity in Model Organisms
- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- Autophagy in Disease and Therapy
- Neuroscience and Neuropharmacology Research
- Plant Molecular Biology Research
- 3D Printing in Biomedical Research
- Neurogenetic and Muscular Disorders Research
- Evolution and Genetic Dynamics
- Nuclear Receptors and Signaling
- Adipose Tissue and Metabolism
- Stroke Rehabilitation and Recovery
- Barrier Structure and Function Studies
Munich Cluster for Systems Neurology
2020-2025
Ludwig-Maximilians-Universität München
2012-2025
LMU Klinikum
2019-2024
Synergy University
2023
German Center for Neurodegenerative Diseases
2009-2021
Rockefeller University
2014-2021
Center for Integrated Protein Science Munich
2007
Degeneration of dopaminergic neurons in the substantia nigra is characteristic for Parkinson's disease (PD), second most common neurodegenerative disorder. Mitochondrial dysfunction believed to contribute etiology PD. Although cases are sporadic, recent evidence points a number genes involved familial variants Among them, loss-of-function phosphatase and tensin homolog-induced kinase 1 (PINK1; PARK6) associated with rare autosomal recessive parkinsonism. In HeLa cells, RNA...
Our aging society is confronted with a dramatic increase of patients suffering from tauopathies, which include Alzheimer disease and certain frontotemporal dementias. These disorders are characterized by typical neuropathological lesions including hyperphosphorylation subsequent aggregation TAU protein neuronal cell death. Currently, no mechanism-based cures available. We generated fluorescently labeled transgenic zebrafish, rapidly recapitulated key pathological features phosphorylation...
Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between makes it challenging to replicate key findings integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC deeply characterized their genetic properties using whole genome sequencing, genomic stability upon CRISPR-Cas9-based gene editing, including differentiation commonly used types. These studies...
CRISPR genome editing is a promising tool for translational research but can cause undesired outcomes, both on target at the edited locus and off other genomic loci. Here, we investigate occurrence of deleterious on-target effects (OnTEs) in human stem cells after insertion disease-related mutations by homology-directed repair (HDR) gene using non-homologous end joining (NHEJ). We identify large, mono-allelic deletions loss-of-heterozygosity escaping standard quality controls up to 40%...
Haploinsufficiency of the progranulin (PGRN)‐encoding gene (GRN) causes frontotemporal lobar degeneration (GRN‐FTLD) and results in microglial hyperactivation, TREM2 activation, lysosomal dysfunction, TDP‐43 deposition. To understand contribution hyperactivation to pathology, we used genetic pharmacological approaches suppress TREM2‐dependent transition microglia from a homeostatic disease‐associated state. Trem2 deficiency Grn KO mice reduced hyperactivation. explore antibody‐mediated...
Imbalances in the amounts of amyloid-β peptides (Aβ) generated by membrane proteases β- and γ-secretase are considered as a trigger Alzheimer's disease (AD). Cell-free studies have shown that increasing thickness modulates Aβ generation but it has remained unclear if these effects translatable to cells. Here we show very long-chain fatty acid erucic (EA) triggers acyl chain remodeling AD cell models, resulting substantial lipidome alterations which included increased esterification EA...
Abstract Background Amyloid-β peptide (Aβ) species of 42 or 43 amino acids in length (Aβ42/43) trigger Alzheimer´s disease (AD) and are produced abnormal amounts by mutants the γ-secretase subunit presenilin-1 (PS1), which represent primary cause familial AD (FAD). Lowering these peptides modulators (GSMs) is increasingly considered a safe strategy to treat since compounds do not affect overall cleavage substrates. GSMs were shown modulate only wild-type (WT) but also FAD mutants, expanding...
Mitochondria provide ATP, maintain calcium homeostasis, and regulate apoptosis. Neurons, due to their size complex geometry, are particularly dependent on the proper functioning distribution of mitochondria. Thus disruptions these organelles transport play a central role in broad range neurodegenerative diseases. While vitro studies have greatly expanded our knowledge mitochondrial dynamics, understanding vivo remains limited. To address this shortcoming, we developed tools study dynamics...
The Tau protein is the major component of intracellular filaments observed in a number neurodegenerative diseases known as tauopathies. pathological mutant containing proline-to-leucine mutation at position 301 (P301L) leads to severe human tauopathy. Here, we assess impact FK506-binding with molecular mass ∼52 kDa (FKBP52), an immunophilin that interacts physiological Tau, on Tau-P301L activity. We identify direct interaction FKBP52 and its phosphorylated forms demonstrate FKBP52's ability...
With the emergence of microglia-modulating therapies there is an urgent need for reliable biomarkers to evaluate microglial activation states.Using mouse models and human induced pluripotent stem cell-derived microglia (hiMGL), genetically modified yield most opposite homeostatic (TREM2-knockout) disease-associated (GRN-knockout) states, we identified activity-dependent markers. Non-targeted mass spectrometry was used identify proteomic changes in cerebrospinal fluid (CSF) Grn-...
Background Mutations in the gene encoding E3 ubiquitin ligase parkin (PARK2) are responsible for majority of autosomal recessive parkinsonism. Similarly to other knockout mouse models PD-associated genes, mice do not show a substantial neuropathological or behavioral phenotype, while loss Drosophila melanogaster leads severe including reduced lifespan, apoptotic flight muscle degeneration and male sterility. In order study function more detail address possible differences its role different...
Human-induced-pluripotent-stem-cell (hiPSC)-derived neurons are valuable for investigating brain physiology and disease. Here, we present a protocol to differentiate hiPSCs into cortical with high yield purity. We describe neural induction via dual-SMAD inhibition, followed by spot-based differentiation provide quantities of precursors. detail their enrichment, expansion, purification avoid unwanted cell fates optimal conditions rosette proliferation. These differentiated suitable drug...