A5021103941- Angiogenesis and VEGF in Cancer
- Cell death mechanisms and regulation
- Cell Adhesion Molecules Research
- Erythrocyte Function and Pathophysiology
- Blood properties and coagulation
- Phagocytosis and Immune Regulation
- Receptor Mechanisms and Signaling
- Hippo pathway signaling and YAP/TAZ
- Lymphatic System and Diseases
- Physiological and biochemical adaptations
- Nitric Oxide and Endothelin Effects
- Neurobiology and Insect Physiology Research
- Barrier Structure and Function Studies
- Mitochondrial Function and Pathology
- S100 Proteins and Annexins
- Cancer Cells and Metastasis
- Chemokine receptors and signaling
- Adenosine and Purinergic Signaling
- Congenital heart defects research
- Invertebrate Immune Response Mechanisms
- Platelet Disorders and Treatments
- Ion Transport and Channel Regulation
- Diabetes Treatment and Management
- Telomeres, Telomerase, and Senescence
- Electrospun Nanofibers in Biomedical Applications
Max Planck Institute for Heart and Lung Research
2012-2022
Goethe University Frankfurt
2013-2019
German Centre for Cardiovascular Research
2013
Heinrich Heine University Düsseldorf
2009-2011
Max Planck Society
2006-2010
Max Planck Institute of Molecular Cell Biology and Genetics
2006-2009
The vascular endothelium is constantly exposed to mechanical forces, including fluid shear stress exerted by the flowing blood. Endothelial cells can sense different flow patterns and convert signal of laminar into atheroprotective signals, eNOS activation, whereas disturbed in atheroprone areas induces inflammatory signaling, NF-κB activation. How endothelial distinguish poorly understood. Here we show that both activate same initial pathway involving mechanosensitive cation channel Piezo1,...
Elevated blood pressure is a key risk factor for developing cardiovascular diseases. Blood largely determined by vasodilatory mediators, such as nitric oxide (NO), that are released from the endothelium in response to fluid shear stress exerted flowing blood. Previous work has identified several mechanotransduction signaling processes involved stress-induced endothelial effects, but how initiates poorly understood. Here, we evaluated human and bovine cells found purinergic receptor P2Y2 G...
The extravasation of leukocytes is a critical step during inflammation that requires the localized opening endothelial barrier. This process initiated by close interaction with various adhesion molecules such as ICAM-1 on surface cells. Here we reveal mechanical forces generated leukocyte-induced clustering synergize fluid shear stress exerted flowing blood to increase plasma membrane tension and activate mechanosensitive cation channel PIEZO1. leads increases in [Ca2+]i activation...
Formation of the lymphatic system requires coordinated expression several key regulators: vascular endothelial growth factor C (VEGFC), its receptor FLT4, and a transcriptional effector, PROX1. Yet, how these signaling components is regulated remains poorly understood. Here, using combination genetic molecular approaches, we identify transcription hematopoietically expressed homeobox (HHEX) as an upstream regulator VEGFC, PROX1 during angiogenic sprouting formation in vertebrates. By...
Metastasis is the major cause of death in cancer patients. Circulating tumor cells need to migrate through endothelial layer blood vessels escape hostile circulation and establish metastases at distant organ sites. Here, we identified membrane-bound metalloprotease ADAM17 on as a key driver metastasis. We show that TNFR1-dependent cell–induced cell death, extravasation, subsequent metastatic seeding dependent activity ADAM17. Moreover, reveal ADAM17-mediated TNFR1 ectodomain shedding...
The cytokine interleukin-11 promotes regeneration and limits scar formation in multiple zebrafish tissues after injury.
Significance G protein–coupled receptors (GPCRs) are important regulators of cellular and biological functions primary targets therapeutic drugs. About 100 mammalian GPCRs still considered orphan because they lack a known endogenous ligand. We report the deorphanization GPR182, which is expressed in endothelial cells microvasculature. show that GPR182 an atypical chemokine receptor, binds CXCL10, 12, 13. However, binding does not induce downstream signaling. Consistent with scavenging...
Transforming growth factor-β-activated kinase 1 (TAK1) is a mitogen-activated protein 3-kinase and an AMP-activated (AMPK) in some cell types. Although TAK1(-/-) mice display defects developmental vasculogenesis, the role of TAK1 endothelial cells has not been investigated detail.TAK1 downregulation (small interfering RNA) human attenuated proliferation without inducing apoptosis diminished migration, as well tube formation. Cytokine- vascular factor (VEGF)-induced sprouting modified...
The cardiovascular system of bilaterians developed from a common ancestor. However, no endothelial cells exist in invertebrates demonstrating that primitive tubes do not require this vertebrate-specific cell type order to form. This raises the question how form invertebrates? Here we discovered invertebrate cephalochordate amphioxus, basement membranes endoderm and mesoderm line lumen major vessels, namely aorta heart. During amphioxus development laminin-containing extracellular matrix...
During developmental angiogenesis, blood vessels grow and remodel to ultimately build a hierarchical vascular network. Whether, how, cell death signaling molecules contribute vessel formation is still not well understood. Caspase-8 (Casp-8), key protease in the extrinsic death–signaling pathway, regulates via both apoptosis necroptosis. Here, we show that expression of Casp-8 endothelial cells (ECs) required for proper postnatal retina angiogenesis. EC-specific Casp-8–KO pups (Casp-8ECKO)...
Somatic stem cells expand massively during tissue regeneration, which might require control of cell fitness, allowing elimination non-competitive, potentially harmful cells. How or if such are removed to restore organ function is not fully understood. Here, we show that a substantial fraction muscle (MuSCs) undergo necroptosis because epigenetic rewiring chronic skeletal required for efficient regeneration dystrophic muscles. Inhibition strongly enhances suppression MuSC expansion in...
Endothelial cells are equipped with the intrinsic ability to form tubes and sprouts a central lumen. However, mechanisms that allow endothelial lumen largely unknown. We would like discuss critically current models of vascular formation point many unexplored open questions. briefly present what researchers can learn from other cell systems lumen, such as cysts formed by Madin-Darby Canine Kidney (MDCK) well tracheae Drosophila epithelial cells. In addition, we number questions need be...
Within the tumor microenvironment, cells and endothelial regulate each other. While induce angiogenic responses in cells, release angiocrine factors, which act on other stromal cells. We report that cell–derived adrenomedullin has a pro-angiogenic as well direct tumor-promoting effect, endothelium-derived CC chemokine ligand 2 (CCL2) suppresses adrenomedullin-induced cell proliferation. Loss of receptor CALCRL or G-protein Gs reduced Surprisingly, proliferation was also after deletion Gs....