A5016221048- Platelet Disorders and Treatments
- Chemokine receptors and signaling
- COVID-19 Clinical Research Studies
- Receptor Mechanisms and Signaling
- Macrophage Migration Inhibitory Factor
- Spectroscopy Techniques in Biomedical and Chemical Research
- Genetics, Aging, and Longevity in Model Organisms
- Blood properties and coagulation
- Antiplatelet Therapy and Cardiovascular Diseases
- Cell Adhesion Molecules Research
- Spectroscopy and Chemometric Analyses
- Nuclear Receptors and Signaling
- Circadian rhythm and melatonin
- Complement system in diseases
- Adipokines, Inflammation, and Metabolic Diseases
- Lipoproteins and Cardiovascular Health
- Long-Term Effects of COVID-19
- Signaling Pathways in Disease
- Metabolomics and Mass Spectrometry Studies
- Analytical Chemistry and Chromatography
- Erythrocyte Function and Pathophysiology
- Acute Myocardial Infarction Research
- Angiogenesis and VEGF in Cancer
- Pharmacogenetics and Drug Metabolism
- Cancer-related Molecular Pathways
University of Tübingen
2020-2024
Universitätsklinikum Tübingen
2022-2024
University Children's Hospital Tübingen
2023-2024
University of Potsdam
2013-2017
University of Pennsylvania
2010-2011
Universität Greifswald
2005
The soil-dwelling nematode C. elegans is a powerful system for comparative molecular analyses of environmental stress response mechanisms. Infection worms with bacterial and fungal pathogens causes the activation well-characterized innate immune transcriptional programs in pathogen-exposed hypodermal intestinal tissues. However, pathophysiological events that drive such responses are not understood. Here, we show infection-activated are, large part, recapitulated by either physiological or...
Beyond classical roles in thrombosis and haemostasis, it becomes increasingly clear that platelets contribute as key players to inflammatory processes. The involvement of these processes is often mediated through a variety platelet-derived chemokines which are released upon activation act paracrine autocrine factors. In this study, we investigate CXCL14, newly described platelet chemokine its role thrombus formation well monocyte migration. addition, examine the receptor CXCR4 possible for...
Platelets play a significant role in atherothrombosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is critically involved the regulation of LDL metabolism and interacts with platelet function. The effect PCSK9 function poorly understood. authors this article sought to characterize platelets as major source PCSK9's In large cohort patients coronary artery disease (CAD), count, reactivity, platelet-derived release were analyzed. on monocyte was investigated vitro. Platelet count...
Abstract Platelet activation plays a critical role in thrombosis. Inhibition of platelet is cornerstone treatment acute organ ischemia. ACKR3 surface expression independently associated with all-cause mortality CAD patients. In novel genetic mouse strain, we show that megakaryocyte/platelet-specific deletion results enhanced and thrombosis vitro vivo. Further, performed ischemia/reperfusion experiments (transient LAD-ligation tMCAO) mice to assess the impact deficiency platelets on tissue...
Spatial transcriptomics of histological sections have revolutionized research in life sciences and enabled unprecedented insights into genetic processes involved tissue reorganization. However, contrast to genomic analysis, the actual biomolecular composition sample has fallen behind, leaving a gap potentially highly valuable information. Raman microspectroscopy provides untargeted spatiomolecular information at high resolution, capable filling this gap. In study we demonstrate spatially...
Patients with cardiovascular disease (CVD) are at high risk to develop adverse events. The distinct of developing (CV) events is not solely explained by traditional factors. Platelets essentially involved in progression CVD including coronary artery (CAD) and platelet hyperreactivity leads development CV Alterations the lipidome lead hyperresponsiveness thus might alter individual profile. In this study, we investigate CAD patients untargeted lipidomics elucidate alterations lipid...
Cyclophilin A (CyPA) induces leucocyte recruitment and platelet activation upon release into the extracellular space. Extracellular CyPA therefore plays a critical role in immuno-inflammatory responses tissue injury thrombosis activation. To date, CD147 (EMMPRIN) has been described as primary receptor mediating effects of platelets leucocytes. The for advanced glycation end products (RAGE) shares inflammatory prothrombotic properties also found to have similar ligands CD147. In this study,...
Accumulation of free heme B in the plasma can be result severe hemolytic events, when scavenger system for hemoglobin and is overwhelmed. Free oxidized into toxic hemin, which has been proven to activate platelet degranulation aggregation promote thrombosis. In present study we analyzed effect hemin on activation-mediated lysosomal CD63 surface expression platelets using classic flow cytometry fluorescence microscopy techniques. Classical activators were used as control distinguish novel...
ACKR3, an atypical chemokine receptor, has been associated with prothrombotic events and the development of cardiovascular events. We designed, synthesized, evaluated a series novel small molecule ACKR3 agonists. Extensive structure–activity relationship studies resulted in several promising agonists potencies ranging from low micromolar to nanomolar range, for example, 23 (EC50 = 111 nM, Emax 95%) 27 69 82%) β-arrestin-recruitment assay. These compounds are selective versus ACKR2, CXCR3,...
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The molecular mechanisms of animal cell osmoregulation are poorly understood. Genetic studies in yeast have identified mucin-like proteins as critical regulators osmosensitive signaling and gene expression. Whether mucins play similar roles higher organisms is not known. Here, we show that mutations the Caenorhabditis elegans osm-8 specifically disrupt osmoregulatory physiological processes. In mutants, normal responses to hypertonic stress, such accumulation organic osmolytes activation...
To fulfil its orchestration of immune cell trafficking, a network chemokines and receptors developed that capitalizes on specificity, redundancy, functional selectivity. The discovery heteromeric interactions in the chemokine interactome has expanded complexity within this network. Moreover, some inflammatory mediators, not structurally linked to classical chemokines, bind behave as atypical (ACKs). We identified macrophage migration inhibitory factor (MIF) an ACK binds CXCR2 CXCR4 promote...
The atypical chemokine receptor 3 (ACKR3), formerly known as CXC-chemokine 7 (CXCR7), has been postulated to regulate platelet function and thrombus formation. Herein, we report the discovery development of first-in-class ACKR3 agonists, which demonstrated superagonistic properties with Emax values up 160% compared endogenous reference ligand CXCL12 in a β-arrestin recruitment assay. Initial silico screening using an homology model identified two hits, C10 (EC50 19.1 μM) C11 = 11.4 μM)....
Background Platelets are key players in the pathophysiology of coronary artery disease (CAD) and platelet hyperreactivity leads to increased risk developing adverse cardiovascular events. Further, significant changes lipidome occur patients with acute syndrome (ACS) critically regulated lipids lead hyperresponsiveness. Statin treatment is crucial prevention CAD by remodeling lipid metabolism. Objective In this study, we investigate untargeted lipidomics, highlighting between statin-treated...
Abstract Background Diagnostic approaches like the nuclear magnetic resonance spectroscopy (NMR) based quantification of metabolites, lipoproteins, and inflammation markers has helped to identify typical alterations in blood serum COVID-19 patients. However, confounders such as sex, comorbidities, which strongly influence metabolome, were often not considered. Therefore, aim this NMR study was consider well arterial hypertension (AHT), when investigating COVID-19-positive samples a large...
Hemolysis results in release of free hemoglobin and hemin liberation from erythrocytes. Hemin has been described to induce platelet activation trigger thrombosis. We evaluated the effect on function surface expression collagen receptor glycoprotein VI (GPVI). Isolated platelets were stimulated with increasing concentrations hemin. found that strongly enhanced activation, aggregation, aggregate formation immobilized under flow. In contrast, we GPVI was significantly reduced upon stimulation...
Abstract In vulnerable atherosclerotic plaques intraplaque hemorrhages (IPH) result in hemolysis of red blood cells and release hemoglobin free hemin. Hemin activates platelets leads to thrombosis. Agonism the inhibitory platelet receptor ACKR3 inhibits hemin-dependent activation thrombus formation. To characterize effect hemin agonism on isolated human platelets, multi-color flow cytometry classical experimental setup such as light transmission aggregometry a chamber assay have been used....
In vulnerable atherosclerotic plaques, intraplaque hemorrhages (IPH) result in hemolysis of red blood cells and release hemoglobin free hemin. Hemin activates platelets leads to thrombosis. Agonism the inhibitory platelet receptor ACKR3 inhibits hemin-dependent activation thrombus formation. To characterize effect hemin agonism on isolated human platelets, multi-color flow cytometry classical experimental setup such as light transmission aggregometry a chamber assay were used. induces...
Abstract Background Platelet receptors ACKR3 and CXCR4 play a crucial role in variety of cardio-vascular diseases. Like most chemokine receptors, is G protein coupled receptor that induces platelet activation. In contrast, the atypical 3 (ACKR3) lacks ability to activate heterotrimeric proteins its activation leads inhibition attenuates thrombus formation. nucleated cells, heterodimerization with regulates CXCL12-dependent signaling. The aim our study was investigate formation ACKR3/CXCR4...
Cardiovascular diseases are one of the leading causes mortality worldwide. Therefore, novel therapeutic measures urgently needed, and promising new drug targets must be explored. ACKR3, an atypical chemokine receptor, has been associated with prothrombotic events development cardiovascular events. We designed, synthesized, evaluated a series small molecules ACKR3 agonists. Extensive structure-activity relationship studies resulted in several agonists potencies ranging from low micromolar to...
BACKGROUND: Aortic stenosis (AS) is driven by progressive inflammatory and fibrocalcific processes regulated circulating valve resident endothelial interstitial cells. The impact of platelets, platelet-derived mediators, platelet-monocyte interactions on the acceleration local valvular inflammation mineralization presently unknown. METHODS: We prospectively enrolled 475 consecutive patients with severe symptomatic AS undergoing aortic replacement. Clinical workup included repetitive...
Cardiac hypertrophy is characterized by remodeling of the myocardium, which involves alterations in ECM (extracellular matrix) and cardiomyocyte structure. These critically contribute to impaired contractility relaxation, ultimately leading heart failure. Emerging evidence implicates that extracellular signaling molecules are involved pathogenesis cardiac remodeling. The immunophilin CyPA (cyclophilin A) has been identified as a potential culprit. In this study, we aimed unravel interplay...
Abstract Background Platelet receptors ACKR3 and CXCR4 play a crucial role in variety of cardiovascular diseases. Like most chemokine receptors, is G protein coupled receptor that induces platelet activation. In contrast, the atypical 3 (ACKR3) lacks ability to activate heterotrimeric proteins its activation leads inhibition attenuates thrombus formation. nucleated cells, heterodimerization with regulates CXCL12‐dependent signalling. The aim our study was investigate formation ACKR3/CXCR4...