- Axon Guidance and Neuronal Signaling
- Cancer-related gene regulation
- Hippo pathway signaling and YAP/TAZ
- RNA modifications and cancer
- ATP Synthase and ATPases Research
- Zebrafish Biomedical Research Applications
- Hepatitis C virus research
- Wnt/β-catenin signaling in development and cancer
- Cytokine Signaling Pathways and Interactions
- Angiogenesis and VEGF in Cancer
- Neurogenesis and neuroplasticity mechanisms
- Galectins and Cancer Biology
- Cellular Mechanics and Interactions
- Glycosylation and Glycoproteins Research
- Receptor Mechanisms and Signaling
- Apelin-related biomedical research
- Erythrocyte Function and Pathophysiology
- Optimism, Hope, and Well-being
- Immune Cell Function and Interaction
- Cancer Mechanisms and Therapy
- Cancer Cells and Metastasis
- Biomarkers in Disease Mechanisms
- Cellular transport and secretion
- Retinal Development and Disorders
- Immune cells in cancer
Philipps University of Marburg
2016-2025
Max Planck Institute for Heart and Lung Research
2015-2024
LOEWE Centre for Translational Biodiversity Genomics
2022
Institute of Pharmacology
2016
Max Planck Society
2014-2016
Goethe University Frankfurt
2014
Heidelberg University
2004-2010
Institute of Occupational Medicine
2001
Ludwig-Maximilians-Universität München
2000
Klinikum Vest
2000
The precise spatiotemporal control of cell proliferation is key to the morphogenesis epithelial tissues. Epithelial divisions lead tissue crowding and local changes in force distribution, which turn suppress rate divisions. However, molecular mechanisms underlying this mechanical feedback are largely unclear. Here, we identify a critical requirement B-plexin transmembrane receptors response crowding-induced forces during embryonic skin development. Epidermal stem cells lacking B-plexins fail...
Sema4D-induced activation of plexin-B1 has been reported to evoke different and sometimes opposing cellular responses. The mechanisms underlying the versatility plexin-B1-mediated effects are not clear. Plexin-B1 can associate with receptor tyrosine kinases ErbB-2 Met. Here we show that inactivation RhoA require Met, respectively. In breast carcinoma cells, Sema4D have pro- anti-migratory depending on presence exchange two is sufficient convert response from vice versa. This work identifies...
Semaphorins and their receptors, plexins, have emerged as important cellular cues regulating key developmental processes. B-type plexins directly regulate the actin cytoskeleton in a variety of cell types. Recently, been shown to be expressed striking patterns nervous system over critical windows. However, contrast well characterized plexin-A family, functional role plexin-B proteins neural development organogenesis vertebrates vivo is not known. Here, we elucidated contribution two...
Diagnosis of metastatic breast cancer is associated with a very poor prognosis. New therapeutic targets are urgently needed, but their development hampered by lack understanding the mechanisms leading to tumor metastasis. Exemplifying this fact that approximately 30% all cancers overexpressing receptor tyrosine kinase ErbB-2 characterized high potential and prognosis, signaling events downstream drive cell invasion metastasis remain incompletely understood. Here we show overexpression in...
The accumulation of intratumoral CD8+ T cells is associated with the survival high grade serous ovarian carcinoma patients, but it unclear which cell subsets contribute to this effect and how they are affected by peritoneal tumor microenvironment. Here, we provide evidence for a functional link between long relapse-free survival, effector memory (TEM) in effusion (ascites), level TEM attracting chemokine CXCL9, produced macrophages as major source. We also propose novel mechanism...
A central reason behind the poor clinical outcome of patients with high-grade serous carcinoma (HGSC) ovary is difficulty in reliably detecting early occurrence or recurrence this malignancy. Biomarkers that provide reliable diagnosis disease are therefore urgently needed. Systematic proteomic methods identify HGSC-associated molecules may such biomarkers. We applied antibody-based proximity extension assay (PEA) platform (Olink) for identification proteins upregulated plasma OC patients....
Abstract Background IL‐17A and TNF synergistically promote inflammation tumorigenesis. Their interplay impact on ovarian carcinoma (OC) progression are, however, poorly understood. We addressed this question focusing mesothelial cells, whose interaction with tumor cells is known to play a pivotal role in transcoelomic metastasis formation. Methods Flow‐cytometry immunohistochemistry experiments were employed identify cellular sources of TNF. Changes transcriptomes secretomes determined by...
Significance Plexins, a family of transmembrane receptors for semaphorins, control diverse biological processes during mouse development. However, it is largely unknown through which signaling pathways they exert their functions in vivo. Using an allelic series transgenic mice, we show that the GTPase activating protein domain plexins constitutes key module development, required proper formation nervous, cardiovascular, and skeletal system. In contrast, development liver vasculature...
The peritoneal fluid of ovarian carcinoma patients promotes cancer cell invasion and metastatic spread with lysophosphatidic acid (LPA) as a potentially crucial mediator. However, the origin LPA in ascites clinical relevance individual species have not been addressed. Here, we show that levels multiple acyl-LPA are strongly elevated versus plasma associated short relapse-free survival. Data derived from transcriptome secretome analyses primary ascite-derived cells indicate (a) major route...
Ovarian cancer is characterized by early transcoelomic metastatic spread via the peritoneal fluid, where tumor cell spheroids (TU), tumor-associated T cells (TAT), and macrophages (TAM) create a unique microenvironment promoting progression, chemoresistance, immunosuppression. However, underlying signaling mechanisms remain largely obscure. To chart these networks, we performed comprehensive proteomic transcriptomic analyses of TU, TAT, TAM from ascites ovarian patients. We identify multiple...
The peritoneal fluid (ascites), replete with abundant tumor-promoting factors and extracellular vesicles (EVs) reflecting the tumor secretome, plays an essential role in ovarian high-grade serous carcinoma (HGSC) metastasis immune suppression.A comprehensive picture of mediators impacting HGSC progression is, however, not available.Methods: Proteins ascites from patients were quantified by aptamer-based SOMAscan affinity proteomic platform.SOMAscan data analyzed bioinformatic methods to...
Mutations in the TMEM260 gene cause structural heart defects and renal anomalies syndrome, but function of encoded protein remains unknown. We previously reported wide occurrence O-mannose glycans on extracellular immunoglobulin, plexin, transcription factor (IPT) domains found hepatocyte growth receptor (cMET), macrophage-stimulating (RON), plexin receptors, further demonstrated that two known O-mannosylation systems orchestrated by POMT1/2 transmembrane tetratricopeptide repeat-containing...
Introduction We here thought to dissect the inflammatory signature in lesions of three skin disorders, which show a common adaptive immune response against autoantigens but are characterized by diverging clinical phenotypes. Pemphigus vulgaris (PV) and bullous pemphigoid (BP) type-2-dependent, IgG autoantibody-driven blistering disorders mucous membranes skin, target desmoglein (Dsg)3 (BP)180, respectively. In contrast, lichen planus (LP) is chronic disease with pronounced dermal T cell...
Virus-specific CD4+ T-cell response at the site of inflammation is believed to play a decisive role for course viral disease. In hepatitis C virus (HCV) infection, majority studies focused on peripheral blood response. this study we analyzed intrahepatic virus-specific and compared with that in blood. Liver blood-derived lines were studied 36 patients (18 chronic 18 HCV-associated cirrhosis). interferon gamma (IFN-γ) production single cell level various HCV-proteins (core, nonstructural [NS]...
Abstract Semaphorins and their receptors play important roles in patterning the connectivity of developing nervous system recent data suggest that members plexin‐B family semaphorin may be involved axonal guidance. Here we show mRNAs three genes, plxnb1 , plxnb2 plxnb3 (plexin‐B1, plexin‐B2 plexin‐B3), respectively, are expressed highly specific non‐redundant patterns peripheral central components over defined periods during murine development. Whereas plexin‐B1 strongly neuroepithelium...
Semaphorins comprise a large family of ligands that regulate key cellular functions through their receptors, plexins. In this study, we show the transmembrane semaphorin 4A (Sema4A) can also function as receptor, rather than ligand, and transduce signals triggered by binding Plexin-B1 reverse signaling. Functionally, Sema4A signaling regulates migration various cancer cells well dendritic cells. By combining mass spectrometry analysis with small interfering RNA screening, identify polarity...
Aberrant fear is a cornerstone of several psychiatric disorders. Consequently, there large interest in elucidation signaling mechanisms that link extracellular cues to changes neuronal function and structure brain pathways are important the generation maintenance memory its behavioral expression. Members Plexin-B family receptors for class 4 semaphorins play roles developmental plasticity neurons, their expression persists some areas adult nervous system. Here, we aimed elucidate role...
<title>Abstract</title> Oral administration remains the most accessible and patient-friendly route for drug delivery. Paclitaxel, a potent anticancer agent sourced from natural origins, presents highly lipophilic profile, demonstrates substantial antineoplastic efficacy across various malignancies. However, its clinical application is limited by intrinsic hurdles, including low solubility, systemic toxicity, bioavailability. In this study, we engineered folate-modified zein nanoparticles...