Gisela G. Slaats
A5040640163- Genetic and Kidney Cyst Diseases
- Renal and related cancers
- Tissue Engineering and Regenerative Medicine
- Protist diversity and phylogeny
- Biomedical Research and Pathophysiology
- Hedgehog Signaling Pathway Studies
- Renal cell carcinoma treatment
- Epigenetics and DNA Methylation
- Sulfur Compounds in Biology
- Urological Disorders and Treatments
- Fetal and Pediatric Neurological Disorders
- Organ Donation and Transplantation
- Electrospun Nanofibers in Biomedical Applications
- Glycosylation and Glycoproteins Research
- Amino Acid Enzymes and Metabolism
- Heme Oxygenase-1 and Carbon Monoxide
- Genetic Syndromes and Imprinting
- Bladder and Urothelial Cancer Treatments
- Folate and B Vitamins Research
- Lysosomal Storage Disorders Research
- Retinal Development and Disorders
- 3D Printing in Biomedical Research
- Genomic variations and chromosomal abnormalities
- DNA Repair Mechanisms
- Renin-Angiotensin System Studies
University Medical Center Utrecht
2012-2024
Utrecht University
2012-2023
University Hospital Cologne
2018-2022
University of Cologne
2018-2022
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2018-2022
Stanford University
2015
Heidelberg University
2013-2015
University Hospital Heidelberg
2013-2015
The multinational SYSCILIA consortium aims to gain a mechanistic understanding of the cilium. We utilize multiple parallel high-throughput (HTP) initiatives develop predictive models relationships between complex genotypes and variable phenotypes ciliopathies. generated are only as good wet laboratory data fed into them. It is therefore essential orchestrate well-annotated high-confidence dataset be able assess quality any HTP dataset. Here, we present inaugural gold standard known ciliary...
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....
Pluripotent stem cell-derived kidney organoids offer a promising solution to renal failure, yet current organoid protocols often lead off-target cells and phenotypic alterations, preventing maturity. Here, various dynamic hydrogel architectures are created, conferring controlled biomimetic environment for encapsulation. How stiffness stress relaxation affect phenotype undesired fibrotic markers investigated. The authors observe that stiff encapsulation leads an absence of certain cell types...
Cilia are essential organelles in multiple organ systems, including the kidney where they serve as important regulators of renal homeostasis. Renal nephron cilia emanate from apical membrane epithelia, extending into lumen function flow-sensing and ligand-dependent signaling cascades. Ciliary dysfunction underlies cyst formation that is part caused by deregulation planar cell polarity canonical Wnt signaling. cancer pathologies occur sporadically or heritable syndromes germline mutations...
Significance The molecular mechanisms underlying the juvenile onset cystic kidney disease nephronophthisis, remain incompletely understood. Our mutant mouse model identifies abnormal Hedgehog signaling as primary lesion in although currently perceived knowledge is that aberrant wingless-int responsible. Primary collecting duct cells isolated from mice with nephronophthisis are morphologically and functionally rescued when stimulated. This finding was replicated ex vivo cultured urine-derived...
We recently reported that centrosomal protein 164 (CEP164) regulates both cilia and the DNA damage response in autosomal recessive polycystic kidney disease nephronophthisis. Here we examine functional role of CEP164 nephronophthisis-related ciliopathies concomitant fibrosis. Live cell imaging RPE-FUCCI (fluorescent, ubiquitination-based cycle indicator) cells after siRNA knockdown revealed an overall quicker than control cells, although early S-phase was significantly longer. Follow-up FACS...
Nephronophthisis-related ciliopathies (NPHP-RCs) are developmental and degenerative kidney diseases that frequently associated with extrarenal pathologies such as retinal degeneration, obesity, intellectual disability. We recently identified mutations in a gene encoding the centrosomal protein SDCCAG8 causing NPHP type 10 humans. To study role of Sdccag8 disease pathogenesis, we generated gene-trap mouse line. Homozygous Sdccag8(gt/gt) mice lacked wild-type transcript protein, recapitulated...
Juvenile ciliopathy syndromes that are associated with renal cysts and premature failure commonly the result of mutations in gene encoding centrosomal protein CEP290. In addition to centrosomes transition zone at base primary cilium, CEP290 also localizes nucleus; however, nuclear function is unknown. Here, we demonstrate reduction cellular human mouse kidney cells as well zebrafish embryos leads enhanced DNA damage signaling accumulation breaks ex vivo vivo. Compared those from WT mice,...
<h3>Background</h3> Joubert syndrome (JS) is a recessive ciliopathy characterised by distinctive brain malformation 'the molar tooth sign'. Mutations in >27 genes cause JS, and mutations 12 of these also Meckel-Gruber (MKS). The goals this work are to describe the clinical features <i>MKS1</i>-related JS determine whether disease causing <i>MKS1</i> affect cellular phenotypes such as cilium number, length protein content potential mechanisms underlying JS. <h3>Methods</h3> We measured...
Ciliopathies give rise to a multitude of organ-specific pathologies; obtaining relevant primary patient material is useful for both diagnostics and research. However, acquisition ciliated cells from patients, particularly pediatric presents multiple difficulties. Biopsies blood samples are invasive, patients (and their parents) may be reluctant travel medical centers, especially research purposes. We sought develop non-invasive methods viable ciliopathy which could obtained in the home...
Abstract Fabry disease is a lysosomal storage disorder resulting from impaired alpha-galactosidase A (α-Gal A) enzyme activity due to mutations in the GLA gene. Currently, powerful diagnostic tools and vivo research models study are missing, which major obstacle for further improvements diagnosis therapy. Here, we explore utility of urine-derived primary cells patients. Viable were isolated cultured fresh urine void. The obtained cell culture, modeling renal epithelium, characterized by...
Tissue-engineered grafts for cardiovascular structures experience biochemical stimuli and mechanical forces that influence tissue development after implantation such as the immunological response, oxidative stress, hemodynamic shear strain. Endothelial cells are a cell source of major interest in vascular engineering because their ability to form luminal antithrombotic monolayer. In addition, through undergo endothelial mesenchymal transition (EndMT), may yield type capable increased...
ABSTRACT To investigate the contribution of ion channels to ciliogenesis, we carried out a small interfering RNA (siRNA)-based reverse genetics screen all in mouse genome murine inner medullary collecting duct kidney cells. This revealed four candidate channel genes: Kcnq1, Kcnj10, Kcnf1 and Clcn4. We show that these localize renal tubules, specifically base primary cilia. report human KCNQ1 Long QT syndrome disease alleles regulate ciliogenesis; KCNQ1-p.R518X, -p.A178T -p.K362R could not...
Cilia are sensory organelles that project from the surface of almost all cells. Nephronophthisis (NPH) and NPH-related ciliopathies degenerative genetic diseases caused by mutation cilia-associated genes. These kidney disorders characterized progressive loss functional tubular epithelial cells which is associated with inflammation, fibrosis, cyst formation, ultimately leading to end-stage renal disease. However, disease mechanisms remain poorly understood. Here, we show targeted deletion...