A5034103031- Lymphatic System and Diseases
- Vascular Malformations and Hemangiomas
- Lymphatic Disorders and Treatments
- Angiogenesis and VEGF in Cancer
- Planarian Biology and Electrostimulation
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Genetic and Kidney Cyst Diseases
- Galectins and Cancer Biology
- Neurogenetic and Muscular Disorders Research
- Cutaneous lymphoproliferative disorders research
- Hippo pathway signaling and YAP/TAZ
- Renal and related cancers
- Chemokine receptors and signaling
- Cancer Cells and Metastasis
- Cardiovascular Health and Disease Prevention
- Neonatal Respiratory Health Research
- Congenital heart defects research
- Sympathectomy and Hyperhidrosis Treatments
- Axon Guidance and Neuronal Signaling
- Advanced Neural Network Applications
- Wound Healing and Treatments
- Icing and De-icing Technologies
- Lysosomal Storage Disorders Research
- Genomics and Rare Diseases
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2022-2025
Charité - Universitätsmedizin Berlin
2020-2025
Max Planck Institute for Molecular Biomedicine
2013-2024
Max Planck Institute for Molecular Genetics
2022-2024
Humboldt-Universität zu Berlin
2021-2024
Freie Universität Berlin
2021-2024
St George's, University of London
2020
Max Planck Society
2011-2014
The endothelial Tie1 receptor is ligand-less, but interacts with the Tie2 for angiopoietins (Angpt). Angpt2 expressed in tumor blood vessels, and its blockade inhibits angiogenesis. Here we found that deletion from endothelium of adult mice angiogenesis growth by decreasing cell survival without affecting normal vasculature. Treatment VEGF or VEGFR-2 blocking antibodies similarly reduced growth; however, no additive inhibition was obtained targeting both VEGF/VEGFR-2. In contrast, treatment...
Abstract Mouse models are a critical tool for studying human diseases, particularly developmental disorders 1 . However, conventional approaches phenotyping may fail to detect subtle defects throughout the developing mouse 2 Here we set out establish single-cell RNA sequencing of whole embryo as scalable platform systematic genetic models. We applied combinatorial indexing-based 3 profile 101 embryos 22 mutant and 4 wild-type genotypes at embryonic day 13.5, altogether profiling more than...
Lymphatics are essential for cardiac health, and insufficient lymphatic expansion (lymphangiogenesis) contributes to development of heart failure (HF) after myocardial infarction. However, the regulation impact lymphangiogenesis in non-ischaemic cardiomyopathy following pressure-overload remains be determined. Here, we investigated transversal aortic constriction (TAC) C57Bl/6 Balb/c mice, end-stage HF patients.Cardiac function was evaluated by echocardiography, hypertrophy, lymphatics,...
Therapies targeting blood vessels hold promise for autosomal dominant polycystic kidney disease (ADPKD), the commonest inherited disorder causing failure. However, onset and nature of vascular abnormalities in ADPKD are poorly defined. Accordingly, we employed a combination single-cell transcriptomics, three-dimensional imaging with geometric, topological fractal analyses, multimodal magnetic resonance arterial spin labelling to investigate aberrant microvasculature kidneys. Within human...
The lymphatic vascular system plays an active role in immune cell trafficking, inflammation and cancer spread. In order to provide vivo tool improve our understanding of vessel function physiological pathological conditions, we generated characterized a tdTomato reporter mouse crossed it with line expressing Cre recombinase under the control specific promoter Prox1 inducible fashion. We found that fluorescent signal recapitulates expression pattern vessels other known Prox1-expressing...
Lack of investigatory and diagnostic tools has been a major contributing factor to the failure mechanistically understand lymphedema other lymphatic disorders in order develop effective drug surgical therapies. One difficulty understanding true changes lymph vessel pathology from standard 2D tissue sections.VIPAR (volume information-based histopathological analysis by 3D reconstruction data extraction), light-sheet microscopy-based approach for biopsies, is based on digital visualization...
ABSTRACT Hallmarks of autosomal dominant polycystic kidney disease (ADPKD), the most common hereditary anomaly, include expanding fluid-filled epithelial cysts, inflammation, and fibrosis. Despite previous work showing potential vascular-based therapies, renal microvascular alterations in ADPKD, their timing, are poorly understood. Using single-cell transcriptomics human microvasculature, we identify a population endothelial cells adjacent to cysts ADPKD. This pericystic endothelium,...
In the era of high throughput sequencing, special software is required for clinical evaluation genetic variants. We developed REEV (Review, Evaluate and Explain Variants), a user-friendly platform clinicians researchers in field rare disease genetics. Supporting data was aggregated from public sources. compared with seven other tools variant evaluation. (semi-)automatically fills individual ACMG criteria facilitating interpretation. can store phenotype related to case use these similarity...
Recent advances in 3D imaging technologies provide novel insights to researchers and reveal finer more detail of examined specimen, especially the biomedical domain, but also impose huge challenges regarding scalability for automated analysis algorithms due rapidly increasing dataset sizes. In particular, existing research towards vessel network does not consider memory requirements proposed often generates a large number spurious branches structures consisting many voxels. Additionally,...
We have recently shown that genetic replacement of VE-cadherin by a VE-cadherin-α-catenin fusion construct strongly impairs opening endothelial cell contacts during leukocyte extravasation and induction vascular permeability in adult mice. Here we show this mutation leads to lethality at midgestation on clean C57BL/6 background. Investigating the reasons for embryonic lethality, observed lack fetal liver hematopoiesis severe lymphedema but no detectable defects blood vessel formation...
SUMMARY The fetal liver is a hematopoietic organ, hosting diverse and evolving progenitor population. While human organoids derived from pluripotent stem cells (PSCs) mimic aspects of embryonic development, they typically lack the complex niche interaction between hepatic development. We describe generation Fetal Liver-like Organoids (FLOs), that model hepato-hematopoietic interactions previously characterized in mouse models. Developing FLOs first integrate yolk sac-like hemogenic...
Lymphatic vessels are indispensable for tissue fluid homeostasis, transport of solutes and dietary lipids immune cell trafficking. In contrast to blood vessels, which easily visible by their erythrocyte cargo, lymphatic not readily detected in the context. Their invisibility interferes with analysis three-dimensional lymph vessel structure large volumes hampers dynamic intravital studies on function pathofunction. An approach overcome these limitations mouse models, express transgenic...
Primary lymphoedema (PL) syndromes are increasingly recognised as presentations of complex genetic disease, with at least 20 identified causative genes. Recognition clinical patterns is key to diagnosis, research and therapeutics. The defining criteria for one such syndrome, 'WILD syndrome' (
The placenta is the first embryonic organ, representing connection between embryo and mother, therefore necessary for embryo’s growth survival. To meet ever-growing need nutrient gas exchange, maternal spiral arteries undergo extensive remodeling, thus increasing uteroplacental blood flow by 16-fold. However, insufficient remodeling of can lead to severe pregnancy-associated disorders, including but not limited pre-eclampsia. Insufficient endovascular trophoblast invasion plays a key role in...
Abstract Mouse models are a critical tool for studying human diseases, particularly developmental disorders, as well advancing our general understanding of mammalian biology. However, it has long been suspected that conventional approaches phenotyping insufficiently sensitive to detect subtle defects throughout the developing mouse. Here we set out establish single cell RNA sequencing (sc-RNA-seq) whole embryo scalable platform systematic molecular and cellular mouse genetic models. We...
High-quality three-dimensional (3D) microscopy allows detailed, unrestricted and non-destructive imaging of entire volumetric tissue specimens can therefore increase the diagnostic accuracy histopathological analysis. However, commonly used IgG antibodies are oftentimes not applicable to 3D imaging, due their relatively large size consequently inadequate penetration speed. The lack suitable reagents for histopathology be overcome by an emerging class single-domain antibodies, referred as...