A5074440725- Renal and related cancers
- Birth, Development, and Health
- Congenital heart defects research
- Genetic and Kidney Cyst Diseases
- Zebrafish Biomedical Research Applications
- MicroRNA in disease regulation
- Pregnancy and preeclampsia studies
- Helminth infection and control
- Cell Image Analysis Techniques
- Parasitic infections in humans and animals
- Connexins and lens biology
- Neonatal Respiratory Health Research
- Extracellular vesicles in disease
- Barrier Structure and Function Studies
- Assisted Reproductive Technology and Twin Pregnancy
- Developmental Biology and Gene Regulation
- Tissue Engineering and Regenerative Medicine
University Hospital Heidelberg
2018-2024
Heidelberg University
2018-2024
German Centre for Cardiovascular Research
2018-2020
Stockholm University
2013
Despite widespread drug exposure, for example during gestation or in prematurely born children, organ-specific developmental toxicity of most drugs is poorly understood. Developmental and functional abnormalities are a major cause kidney diseases childhood; however, the potential causal relationship to exposure with nephrotoxic nephrogenesis widely unknown. To identify large scale, we established performed an automated high-content screen score phenotypic renal alterations Tg(wt1b:EGFP)...
Endothelial and epithelial barrier function is crucial for the maintenance of physiological processes. The paracellular permeability depends on composition spatial distribution cell-to-cell tight junctions (TJ). Here, we provide an experimental workflow that yields several layers data in setting a single endothelial cell monolayer. Human umbilical vein cells were grown Transwell filters. Transendothelial electrical resistance (TER) 10 kDa FITC dextran flux measured using Alanyl-Glutamine...
Automated high-throughput workflows allow for chemical toxicity testing and drug discovery in zebrafish disease models. Due to its conserved structural functional properties, the pronephros offers a unique model study renal development at larger scale. Ideally, scoring of pronephric phenotypes includes morphological assessments within same larva. However, efficiently upscale such assays, refinement existing methods is required. Here, we describe multiparametric vivo screening pipeline...
Morphogens including Wnt, Hedgehog and BMP proteins are essential during embryonic development early induction of organ progenitors. Besides free diffusion to form signalling gradients, extracellular vesicle- (EV-) mediated morphogen transport was identified as a central mechanism for Wnt- Hh-signalling. Here, we investigated EVs isolated from whole zebrafish embryos potential mechanism. Inhibition EV-secretion leads severe dorsalization phenotypes, reminiscent disrupted BMP-signalling....
Abstract Despite widespread drug exposure, for example during gestation or in prematurely born children, organ-specific developmental toxicity of most drugs is poorly understood. Developmental and functional abnormalities are a major cause kidney diseases childhood; however, the potential causal relationship to exposure with nephrotoxic nephrogenesis widely unknown. To identify large scale, we established performed an automated high-content screen score phenotypic renal alterations...
Abstract Background and Aims In polycystic kidney disease (PKD) cyst formation growth leads to progressive damage. Recognizing the need for effective cyst-inhibitory drugs, we previously performed high-content screening of approved, repurposable drugs in a zebrafish model identified several compounds with activity low toxicity. Here, further tested two compounds, an anthelmintic agent proton pump inhibitor, rodent PKD (PCK rat) their inhibitory GFR-preserving capacity mammals. Method The...
Abstract Background and Aims Cystic kidney diseases represent ciliopathies that can cause vascular damage through renal hypertension. Additionally, there is growing experimental evidence of endothelial cell abnormalities associated with ciliary protein deficiencies. PCK rats, a strain derived from Sprague-Dawley (SD) rats develops both polycystic disease (PKD) liver disease, serve as model for recessive PKD. The rat also presents in non-renal function. Another study our group suggests...
Pharmaceutical drugs and other chemicals can impact organogenesis, either during pregnancy or by postnatal exposure of very preterm infants. Corticosteroids are administered to pregnant women at risk delivery in order reduce neonatal morbidity mortality. In addition, high-dose corticosteroid infants regularly serves maintain blood pressure prevent treat bronchopulmonary dysplasia, a form chronic lung disease prematurely born Despite clinical benefits, there is increasing evidence...
Abstract Background and Aims Polycystic kidney disease (PKD) is a cystic genetic disorder of the kidneys. Vascular abnormalities are most important non-cystic complications in PKD. In present study, we evaluated aortic morphometry vascular function female male PKD/Mhm (Cy/+) rats, an animal model autosomal dominant Method Thoracic rings from six month-old heterozygous (n = 10; 307±4g) 470±24g) age-matched non-affected homozygous (+/+) Control-female 9; 312±6g) Control-male 13; 460±14g) rats...
Abstract Background and Aims Early-onset cystic kidney disease is a clinically genetically heterogeneous overlapping group of rare often severe disorders with limited, mostly symptomatic treatment options. We developed utilized inherited polycystic (PKD) models to search for pharmacological agents that can rescue or mitigate the phenotype. Method A high-content screening platform identification chemical modifiers cyst formation progression in zebrafish genetic nephropathy model (IFT172...