A5019057483- Genetic and Kidney Cyst Diseases
- Renal and related cancers
- Protist diversity and phylogeny
- Genomics and Rare Diseases
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- Immunotherapy and Immune Responses
- Fetal and Pediatric Neurological Disorders
- Hedgehog Signaling Pathway Studies
- Cellular Mechanics and Interactions
- Glycosylation and Glycoproteins Research
- Cystic Fibrosis Research Advances
- RNA Research and Splicing
- Metabolism and Genetic Disorders
- Genetics and Neurodevelopmental Disorders
- Cerebrovascular and genetic disorders
- Organ Donation and Transplantation
- Cellular transport and secretion
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- Immune Response and Inflammation
- Dermatological and Skeletal Disorders
- Metalloenzymes and iron-sulfur proteins
- RNA and protein synthesis mechanisms
Radboud University Nijmegen
2016-2025
Radboud University Medical Center
2016-2025
University Medical Center
2025
Radboud Institute for Molecular Life Sciences
2014-2019
Institut des Maladies Métaboliques et Cardiovasculaires
2011
University of Florence
2010
National Center for Tumor Diseases
2009
Combined Ophthalmic Research Rotterdam
2002
Jeune asphyxiating thoracic dystrophy (JATD) is a rare, often lethal, recessively inherited chondrodysplasia characterised by shortened ribs and long bones, sometimes accompanied polydactyly, renal, liver retinal disease. Mutations in intraflagellar transport (IFT) genes cause JATD, including the IFT dynein-2 motor subunit gene DYNC2H1. Genetic heterogeneity large DYNC2H1 size have hindered JATD genetic diagnosis.To determine contribution to we screened 71 patients combining SNP mapping,...
The cilium is an essential organelle at the surface of mammalian cells whose dysfunction causes a wide range genetic diseases collectively called ciliopathies. current rate which new ciliopathy genes are identified suggests that many ciliary components remain undiscovered. We generated and rigorously analyzed genomic, proteomic, transcriptomic evolutionary data systematically integrated these using Bayesian statistics into predictive score for function. This resulted in 285 candidate genes....
Podosomes are dynamic adhesion structures found in dendritic cells (DCs) and other of the myeloid lineage. We previously showed that prostaglandin E2 (PGE2), an important proinflammatory mediator produced during DC maturation, induces podosome disassembly within minutes after stimulation. Here, we demonstrate this response is mediated by cAMP elevation, occurs downstream Rho kinase dependent on myosin II. Whereas PGE2 stimulation leads to activation small GTPase RhoA, decreased levels...
Assembly and disassembly of adhesion structures such as focal adhesions (FAs) podosomes regulate cell differentiation. On antigen-presenting dendritic cells (DCs), acquisition a migratory immunostimulatory phenotype depends on podosome dissolution by prostaglandin E(2) (PGE(2)). Whereas the effects physico-chemical topographical cues have been extensively studied FAs, little is known about how respond to these signals. Here, we show that, unlike for formation not controlled substrate...
Endocrine-cerebro-osteodysplasia (ECO) syndrome [MIM:612651] caused by a recessive mutation (p.R272Q) in Intestinal cell kinase (ICK) shows significant clinical overlap with ciliary disorders. Similarities are strongest between ECO syndrome, the Majewski and Mohr-Majewski short-rib thoracic dysplasia (SRTD) polydactyly syndromes, hydrolethalus syndrome. In this study, we present novel homozygous ICK fetus compare effect of previously reported variant on ciliogenesis cilium morphology....
Mainzer–Saldino syndrome (MZSDS) is a skeletal ciliopathy and part of the short-rib thoracic dysplasia (SRTD) group ciliary disorders. The main characteristics MZSDS are short limbs, mild narrow thorax, blindness, renal failure. Thus far, variants in two genes associated with MZSDS: IFT140, IFT172. In this study, we describe 1-year-old girl presenting abnormalities, Leber congenital amaurosis, bilateral hearing difficulties. For establishing an accurate diagnosis, combined clinical,...
Background: Persistent splenomegaly, often an incidental finding, can originate from a number of inherited metabolic disorders (IMDs). Variants APOE are primarily known as risk factors in terms cardiovascular disease; however, severe dysfunction result disease phenotype with considerable overlap lysosomal storage (LSDs), including splenomegaly and gross elevation N-palmitoyl-O-phosphocholine-serine (PPCS). Methods: A case study (deep phenotyping, genetic FACS analysis) literature was...
Dendritic cells (DC) take up pathogens through phagocytosis and process them into protein lipid fragments for presentation to T cells. So far, the proteome of human DC phagosome, a detrimental compartment antigen processing as well activation, remains largely uncharacterized. Here we have analyzed composition phagosomes from monocyte-derived DC. For LC-MS/MS analysis purified using latex beads targeted DC-SIGN, quantified proteins label-free method. We used organellar enrichment ranking...
Gene expression is commonly used to study the activation of dendritic cells (DCs) identify proteins that determine whether these induce an immunostimulatory or tolerogenic immune response. RNA expression, however, does not necessarily predict protein abundance and often requires large numbers experiments for statistical significance. Proteomics provides a direct view on but costly time consuming. Here, we combined comprehensive quantitative proteome transcriptome analysis single batch...
Chronic infections are caused by microorganisms that display effective immune evasion mechanisms. Dendritic cell (DC)-dependent T cell-mediated adaptive immunity is one of the mechanisms have evolved to prevent occurrence chronic bacterial infections. In turn, pathogens developed strategies evade recognition. this study, we show gram-negative and gram-positive bacteria differ in their ability activate DCs far more inducers DC maturation. Moreover, observed only can induce loss adhesive...
Background: NANS-CDG is a recently described congenital disorder of glycosylation caused by biallelic genetic variants in NANS , encoding an essential enzyme de novo sialic acid synthesis. Sialic at the end glycoconjugates plays key role biological processes such as brain and skeletal development. Here, we present observational cohort study to delineate genetic, biochemical, clinical phenotype assess possible correlations. Methods: Medical laboratory records were reviewed with retrospective...
Abstract INPP5E encodes inositol polyphosphate-5-phosphatase E, an enzyme involved in regulating the phosphatidylinositol (PIP) makeup of primary cilium membrane. Pathogenic variants hence cause a variety ciliopathies: genetic disorders caused by dysfunctional cilia. While majority these are syndromic, such as neuronal ciliopathy Joubert syndrome, some cases patients will present with isolated phenotype—most commonly non-syndromic retinitis pigmentosa (RP). Here, we report two novel...
<h3>Background</h3> Recent findings suggesting that <i>Abelson helper integration site 1</i> (<i>AHI1</i>) is involved in non-syndromic retinal disease have been debated, as the functional significance of identified missense variants was uncertain. We assessed whether <i>AHI1</i> cause retinitis pigmentosa (RP). <h3>Methods</h3> Exome sequencing performed three probands with RP. The effects were predicted by three-dimensional structure homology modelling. Ciliary parameters evaluated...
Sensenbrenner syndrome, which is also known as cranioectodermal dysplasia (CED), a rare, autosomal recessive ciliary chondrodysplasia characterized by variety of clinical features including distinctive craniofacial appearance well skeletal, ectodermal, liver and renal anomalies. Progressive disease can be life-threatening in this condition. CED genetically heterogeneous disorder. Currently, variants any six genes (IFT122, WDR35, IFT140, IFT43, IFT52 WDR19) have been associated with syndrome....
Skeletal ciliopathies are a group of disorders caused by dysfunction the cilium, small signaling organelle present on nearly every vertebrate cell. This is marked genetic and clinical heterogeneity, which complicates accurate diagnosis. In this study, we developed robust, standardized immunofluorescence approach to accurately diagnose subset these disorders. Hereto determined compared cilium phenotype healthy individuals patients from three different ciliopathy subgroups, using skin-derived...