A5081941586- Cellular transport and secretion
- Genetics and Neurodevelopmental Disorders
- Cell Image Analysis Techniques
- Viral Infections and Vectors
- Mosquito-borne diseases and control
- Plant Virus Research Studies
- Mitochondrial Function and Pathology
- Genomic variations and chromosomal abnormalities
- Genetic Neurodegenerative Diseases
- Neuroscience and Neuropharmacology Research
- RNA Research and Splicing
- Neurological diseases and metabolism
- Parkinson's Disease Mechanisms and Treatments
- Hereditary Neurological Disorders
- Neurogenesis and neuroplasticity mechanisms
- 3D Printing in Biomedical Research
- Brain Tumor Detection and Classification
- CRISPR and Genetic Engineering
- Lipid Membrane Structure and Behavior
- Computational Drug Discovery Methods
- Congenital heart defects research
- Single-cell and spatial transcriptomics
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience of respiration and sleep
- Multiple Sclerosis Research Studies
Heidelberg University
2020-2024
Chica and Heinz Schaller Foundation
2020-2024
Heidelberg University
2023-2024
University of Chile
2016
Abstract MYT1L is an autism spectrum disorder (ASD)-associated transcription factor that expressed in virtually all neurons throughout life. How mutations cause neurological phenotypes and whether they can be targeted remains enigmatic. Here, we examine the effects of deficiency human mice. Mutant mice exhibit neurodevelopmental delays with thinner cortices, behavioural phenotypes, gene expression changes resemble those ASD patients. target genes, including WNT NOTCH , are activated upon...
ABSTRACT The formation of mammalian synapses entails the precise alignment presynaptic release sites with postsynaptic receptors but how nascent cell–cell contacts translate into assembly specializations remains unclear. Guided by pioneering work in invertebrates, we hypothesized that synapses, liprin-α proteins directly link trans -synaptic initial to downstream steps. Here show that, human neurons lacking all four isoforms, synaptic are formed recruitment active zone components and...
Glioblastomas are invasive brain tumors with high therapeutic resistance. Neuron-to-glioma synapses have been shown to promote glioblastoma progression. However, a characterization of tumor-connected neurons has hampered by lack technologies. Here, we adapted retrograde tracing using rabies viruses investigate and manipulate neuron-tumor networks. Glioblastoma rapidly integrated into neural circuits across the brain, engaging in widespread functional communication, cholinergic driving...
Multiple sclerosis (MS) is a progressive inflammatory demyelinating disease of the CNS. Increasing evidence suggests that vulnerable neurons in MS exhibit fatal metabolic exhaustion over time, phenomenon hypothesized to be caused by chronic hyperexcitability. Axonal Kv7 (outward-rectifying) and oligodendroglial Kir4.1 (inward-rectifying) potassium channels have important roles regulating neuronal excitability at around nodes Ranvier. Here, we studied spatial functional relationship between...
Dystonia is a debilitating hyperkinetic movement disorder, which can be transmitted as monogenic trait. Here, we describe homozygous frameshift, nonsense, and missense variants in TSPOAP1, encodes the active-zone RIM-binding protein 1 (RIMBP1), genetic cause of autosomal recessive dystonia 7 subjects from 3 unrelated families. Subjects carrying loss-of-function presented with juvenile-onset progressive generalized dystonia, associated intellectual disability cerebellar atrophy. Conversely,...
Toscana virus is a major cause of arboviral disease in humans the Mediterranean basin during summer. However, early virus-host cell interactions and entry mechanisms remain poorly characterized. Investigating iPSC-derived human neurons lines, we found that binding to surface was specific, 50% bound virions were endocytosed within 10 min. Virions entered Rab5a+ endosomes and, subsequently, Rab7a+ LAMP-1+ late endosomal compartments. Penetration required intact occurred 30 min following...
Glioblastomas are heterogeneous brain tumors, notorious for their invasive behavior and resistance to therapy. Neuron-to-glioma synapses have been identified promote glioblastoma invasion proliferation. However, a comprehensive characterization of tumor-connected neurons has hampered by lack technologies. Here, we adapted retrograde tracing with modified rabies virus system characterize manipulate connected neuron-tumor networks. Glioblastoma rapidly integrated into neural circuits across...
Abstract Presynaptic scaffold proteins, including liprin-α, RIM, and ELKS, are pivotal to the assembly of active zone regulating coupling calcium signals neurotransmitter release, yet underlying mechanism remains poorly understood. Here, we determined crystal structure liprin-α2/RIM1 complex, revealing a multifaceted intermolecular interaction that drives liprin-α/RIM assembly. Neurodevelopmental disease-associated mutations block formation complex. Disrupting this in neurons impairs...
Abstract Glioblastomas are primary brain tumors known for their whole-brain invasion and high therapeutic resistance. In previous studies, neuron-to-glioma synapses have been shown to promote glioblastoma progression. A deep characterization of this communication tumor-connected neurons has not possible due technological limitations. We adapted a rabies virus-based retrograde tracing approach investigate manipulate neuron-tumor networks. Interestingly, we found that cells rapidly integrated...
ABSTRACT Dystonia is a debilitating hyperkinetic movement disorder, frequently transmitted as monogenic trait. Here, we describe homozygous frameshift, nonsense and missense variants in TSPOAP1 , encoding the active zone RIM-binding protein 1 (RIMBP1), novel genetic cause of autosomal recessive dystonia seven subjects from three unrelated families. Subjects carrying loss-of-function presented with juvenile- onset progressive generalized dystonia, associated intellectual disability cerebellar...
Abstract Toscana virus is a major cause of arboviral disease in humans the Mediterranean basin during summer. However, early virus-host cell interactions and entry mechanisms remain poorly characterized. Investigating iPSC-derived human neurons lines, we found that binding to surface was specific but inefficient, 50% bound virions were endocytosed within 10 min. Virions entered Rab5a+ endosomes and, subsequently, Rab7a+ LAMP-1+ late endosomal compartments. Penetration required intact...
<title>Abstract</title> Formation of mammalian synapses entails the precise alignment presynaptic release sites with postsynaptic receptors but how nascent cell-cell contacts translate into assembly specializations remains unclear. Guided by pioneering work in invertebrates, we hypothesized that synapsesLiprin-α proteins directly link trans-synapticinitial to downstream steps. In human neurons lacking all four Liprin-α isoforms, synaptic are formed recruitment active zone components and...
Abstract Glioblastoma are incurable brain tumors characterized by their colonization of the entire and notorious therapeutic resistance. Recently, we discovered long membrane tubes called tumor microtubes contributing to invasion, network formation tumor-tumor networks Subsequently, heterogeneous neurons glioblastoma cells were characterized, which can communicate synaptic perisynaptic contacts as well paracrine mechanisms. Currently used models studying neuron-glioblastoma interactions...