A5029224282- Cellular transport and secretion
- Genetic and rare skin diseases.
- Hedgehog Signaling Pathway Studies
- Mitochondrial Function and Pathology
- Cancer and Skin Lesions
- Metabolism and Genetic Disorders
- Ion channel regulation and function
- Endoplasmic Reticulum Stress and Disease
- Retinal Development and Disorders
- Zebrafish Biomedical Research Applications
- Hereditary Neurological Disorders
- Neuroscience and Neuropharmacology Research
- RNA modifications and cancer
- Ion Channels and Receptors
- Genetics and Neurodevelopmental Disorders
- Cardiomyopathy and Myosin Studies
- Photoacoustic and Ultrasonic Imaging
- Erythrocyte Function and Pathophysiology
- CRISPR and Genetic Engineering
- Bone Metabolism and Diseases
- Trace Elements in Health
- Advanced Fluorescence Microscopy Techniques
- Cardiac Arrhythmias and Treatments
- Cardiac electrophysiology and arrhythmias
- Calcium signaling and nucleotide metabolism
Maastricht University
2016-2023
Maastricht University Medical Centre
2015-2021
KU Leuven
2003-2019
Rega Institute for Medical Research
2019
Royal Netherlands Academy of Arts and Sciences
2011
Hubrecht Institute for Developmental Biology and Stem Cell Research
2010
University of Ferrara
2001
Mitochondrial disorders, characterized by clinical symptoms and/or OXPHOS deficiencies, are caused pathogenic variants in mitochondrial genes. However, some of these genes can lead to manifestations which overlap with other neuromuscular diseases, be non-mitochondrial as well. found the DNA (mtDNA) or any 1,500 nuclear a function. We have performed two-step next-generation sequencing approach cohort 117 patients, mostly children, whom disease-cause could likely possibly explain phenotype. A...
Background Neuropathic pain is common in peripheral neuropathy. Recent genetic studies have linked pathogenic voltage-gated sodium channel (VGSC) variants to human disorders. Our aims are determine the frequency of SCN9A , SCN10A and SCN11A patients with pure small fibre neuropathy (SFN), analyse their clinical features provide a rationale for screening. Methods Between September 2009 January 2017, 1139 diagnosed SFN at our reference centre were screened variants. Pathogenicity was...
ATP2C1, encoding the human secretory pathway Ca2+/Mn2+ ATPase (hSPCA1), was recently identified as defective gene in Hailey-Hailey Disease (HHD), an autosomal dominant skin disorder characterized by persistent blisters and erosions. To investigate underlying cause of HHD, we have analyzed changes expression level function hSPCA1 caused mutations found HHD patients. Mutations were introduced into hSPCA1d, a novel splice variant expressed keratinocytes, described here for first time. Encoded...
For many years bone research has been mainly performed in mice, chicken, cell culture systems or human material from the clinic. In this review, we describe features of zebrafish (Danio rerio), a relatively new model system field. This small teleost offers possibilities which make it great complement to mouse: forward genetic screens are possible fish due extrauterine development and large brood size, recent generation osteoblast-specific reporter lines allows visualization osteoblasts vivo....
Calcium is an essential ion serving a multitude of physiological roles. Aside from its role as second messenger, it component the vertebrate bone matrix. Efficient uptake and storage calcium are therefore indispensable for all vertebrates. Transient receptor potential family, vanilloid type (TRPV)5 TRPV6 channels known players in transcellular uptake, but exact contribution this pathway unclear. We used forward genetic screening zebrafish (Danio rerio) to identify genes formation identified...
In recent years, it has been well established that the Ca2+ concentration in lumen of intracellular organelles is a key determinant cell function. Despite fact essential functions Golgi apparatus depend on and Mn2+ its lumen, little known transport system responsible for ion accumulation. The pump PMR1 functionally studied only yeast. humans, mutations orthologous geneATP2C1 cause Hailey-Hailey disease. We report here identification homologue model organismCaenorhabditis elegans after...
Neural cell differentiation involves a complex regulatory signal transduction network in which Ca 2+ ions and the secretory pathway play pivotal roles. The -ATPase isoform 1 (SPCA1) is found Golgi apparatus where it actively involved transport of or Mn from cytosol to lumen. Its expression during brain development different types neurons has been documented recently, raises possibility that SPCA1 contributes neuronal differentiation. In present study, we investigated potential impact on...
In establishing a genetic diagnosis in heterogeneous neurological disease, clinical characterization and whole exome sequencing (WES) go hand-in-hand. Clinical data are essential, not only to guide WES variant selection define the severity of defect, but also identify other patients with defects same gene. an infant patient sensorineural hearing loss, psychomotor retardation epilepsy, resulted identification novel homozygous CLPP frameshift mutation (c.21delA). Based on gene defect symptoms,...
Cytosolic Ca<sup>2+</sup> oscillations can be due to cycles of release and re-uptake internally stored Ca<sup>2+</sup>. To investigate the nature these Ca<sup>2+</sup>stores, we expressed Pmr1 pump of<i>Caenorhabditis elegans</i> in COS-1 cells pretreated with thapsigargin prevent uptake by sarco(endo)plasmic reticulum Ca<sup>2+</sup>-ATPase. co-localized Golgi-specific 58K protein was targeted a store that less leaky for than endoplasmic whose inositol trisphosphate receptors were sensitive...
Human secretory pathway Ca2+/Mn2+-ATPase (SPCA) 2 encoded by ATP2C2 is only expressed in a limited number of tissues, unlike the ubiquitously SPCA1 pump (encoded ATP2C1, gene defective Hailey-Hailey disease). It has not been determined whether there are significant functional differences between and SPCA2 enzymes. Therefore, steady-state transient kinetic approaches were used to characterize overall partial reactions Ca2+ transport cycle mediated human enzyme upon heterologous expression...
In a previous study we overexpressed the thapsigargin (tg)-insensitive Pmr1 Ca<sup>2+</sup> pump of Golgi apparatus <i>Caenorhabditis elegans</i> in COS-1 cells and studied properties store into which it was integrated. Here assessed an endogenous tg-insensitive nonmitochondrial A7r5 16HBE14o− cells, express mammalian homologue Pmr1. The considerably less leaky for than sarco(endo)plasmic-reticulum Ca<sup>2+</sup>-ATPase (SERCA)-containing store. Moreover like worm expressed accumulation...