A5068007651- Neuroinflammation and Neurodegeneration Mechanisms
- Glycosylation and Glycoproteins Research
- Pancreatic function and diabetes
- Genetics and Neurodevelopmental Disorders
- Immune cells in cancer
- Functional Brain Connectivity Studies
- RNA regulation and disease
- Tryptophan and brain disorders
- Redox biology and oxidative stress
- Stress Responses and Cortisol
- Neurogenesis and neuroplasticity mechanisms
- Peroxisome Proliferator-Activated Receptors
- Zebrafish Biomedical Research Applications
Erasmus MC
2018-2024
Utrecht University
2019
University Medical Center Utrecht
2018-2019
Microglia are brain-resident macrophages with trophic and phagocytic functions. Dominant loss-of-function mutations in a key microglia regulator, colony-stimulating factor 1 receptor (CSF1R), cause adult-onset leukoencephalopathy axonal spheroids pigmented glia (ALSP), progressive white matter disorder. Because it remains unclear precisely how CSF1R affect microglia, we generated an allelic series of csf1r mutants zebrafish to identify csf1r-dependent changes. We found that led aberrant...
Developmental and/or epileptic encephalopathies (DEEs) are a group of devastating genetic disorders, resulting in early-onset, therapy-resistant seizures and developmental delay. Here we report on 22 individuals from 15 families presenting with severe form intractable epilepsy, delay, progressive microcephaly, visual disturbance similar minor dysmorphisms. Whole exome sequencing identified recurrent, homozygous variant (chr2:64083454A > G) the essential UDP-glucose pyrophosphorylase (UGP2)...
Abstract Tissue-resident macrophages of the brain, including microglia, are implicated in pathogenesis various CNS disorders and possible therapeutic targets by their chemical depletion or replenishment hematopoietic stem cell therapy. Nevertheless, a comprehensive understanding microglial function consequences human brain is lacking. In disease, heterozygous variants CSF1R , encoding Colony-stimulating factor 1 receptor, can lead to adult-onset leukoencephalopathy with axonal spheroids...
Genetic, epidemiological, and biomarker studies suggest that the immune system is involved in pathogenesis of bipolar disorder (BD). It has therefore been hypothesized activation microglia, resident cells brain, associated with disease. Only a few have addressed involvement microglia BD so far more detailed profiling microglial lacking. Here, we applied multi-level approach to determine state post-mortem brain tissue. We did not find differences density, mRNA expression markers medial...
Abstract Biallelic variants in thioredoxin-related transmembrane 2 protein (TMX2) can cause a brain malformation of cortical development (MCD), characterized by primary microcephaly, polymicrogyria and pachygyria an unknown mechanism. To better understand visualize how TMX2 loss disrupts vivo we investigated the function TMX2, using zebrafish embryo as model system. We generated deficient for ortholog tmx2b , which during first days post fertilization (dpf) showed normal behavioral activity...
Abstract Developmental and/or epileptic encephalopathies (DEEs) are a group of devastating genetic disorders, resulting in early onset, therapy resistant seizures and developmental delay. Here we report on 12 individuals from 10 families presenting with severe form intractable epilepsy, delay, progressive microcephaly visual disturbance. Whole exome sequencing identified recurrent, homozygous variant (chr2:64083454A>G) the essential UDP-glucose pyrophosphorylase ( UGP2 ) gene all...
Schizophrenia (SZ) and bipolar disorder (BD) are severe psychiatric disorders that not easily distinguishable based on clinical measures. Offspring of patients with SZ or BD have a tenfold increased risk developing the as well an for other mental disorders. Reliable identification these subjects might allow early recognition intervention, which been shown to be beneficial treatment outcome may even prevent transition illness. Based abundant evidence associated structural brain abnormalities,...