A5020991402- RNA Research and Splicing
- RNA regulation and disease
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Immune Cell Function and Interaction
- Sirtuins and Resveratrol in Medicine
- Cell Adhesion Molecules Research
- Neuroscience and Neuropharmacology Research
- Ubiquitin and proteasome pathways
- Inflammasome and immune disorders
- Heme Oxygenase-1 and Carbon Monoxide
- Curcumin's Biomedical Applications
- Autophagy in Disease and Therapy
- Kidney Stones and Urolithiasis Treatments
- Viral gastroenteritis research and epidemiology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- CAR-T cell therapy research
- Amphibian and Reptile Biology
- Immune Response and Inflammation
- Immune cells in cancer
- Animal Behavior and Welfare Studies
- Cancer Cells and Metastasis
- NF-κB Signaling Pathways
- Genetics and Neurodevelopmental Disorders
- Virus-based gene therapy research
Ludwig-Maximilians-Universität München
2016-2025
Urologische Klinik München
2017-2024
Washington University in St. Louis
2023
Meyer Children's Hospital
2023
Karolinska Institutet
2023
Technical University of Munich
2019-2022
LMU Klinikum
2018-2021
Technion – Israel Institute of Technology
1957-1959
Crystals cause injury in numerous disorders, and induce inflammation via the NLRP3 inflammasome, however, it remains unclear how crystals cell death. Here we report that of calcium oxalate, monosodium urate, pyrophosphate dihydrate cystine trigger caspase-independent death five different types, which is blocked by necrostatin-1. RNA interference for receptor-interacting protein kinase 3 (RIPK3) or mixed lineage domain like (MLKL), two core proteins necroptosis pathway, blocks crystal...
Neutrophil extracellular trap (NET) formation contributes to gout, autoimmune vasculitis, thrombosis, and atherosclerosis. The outside‐in signaling pathway triggering NET is unknown. Here, we show that the receptor‐interacting protein kinase (RIPK)‐1‐stabilizers necrostatin‐1 or necrostatin‐1s mixed lineage domain‐like (MLKL)‐inhibitor necrosulfonamide prevent monosodium urate (MSU) crystal‐ PMA‐induced in human mouse neutrophils. These compounds do not affect PMA‐ crystal‐induced production...
To overcome the limitations of animal-based experiments, 3D culture models mimicking tumor microenvironment in vivo are gaining attention. Herein, we investigated an alginate-based scaffold for screening 5-fluorouracil (5-FU) or/and curcumin on malignancy colorectal cancer cells (CRC).
Translation of the expanded (ggggcc)n repeat in C9orf72 patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) causes abundant poly-GA inclusions. To elucidate their role pathogenesis, we generated transgenic mice expressing codon-modified (GA)149 conjugated cyan fluorescent protein (CFP). Transgenic progressively developed inclusions predominantly motoneurons interneurons spinal cord brain stem deep cerebellar nuclei. Poly-GA co-aggregated p62, Rad23b newly...
Sirt1 is a NAD+-dependent protein-modifying enzyme involved in regulating gene expression, DNA damage repair, metabolism and survival, as well acts an important subcellular target of resveratrol. The complex mechanisms underlying signaling during carcinogenesis remain controversial, it can serve both tumor promoter suppressor. Whether resveratrol-mediated chemopreventive effects are mediated via CRC growth metastasis remains unclear; which was the subject this study. We found that...
Objective: Resveratrol, a safe and multitargeted natural agent, has been linked with inhibition of survival invasion tumor cells. Tumor Necrosis Factor-β (TNF-β) (Lymphotoxin α) is known as an inflammatory cytokine, however, the underlying mechanisms for its pro-carcinogenic effects whether resveratrol can suppress these in microenvironment are poorly understood. Methods: We investigated modulates 5-Fluorouracil (5-FU) TNF-β on malignant potential human colorectal cancer (CRC) cells (HCT116)...
The human body is exposed to a wide range of particles industrial, environmental or internal origin such as asbestos, alum, silica crystals urate, calcium phosphate, oxalate, cystine cholesterol. Phagocytic clearance involves neutrophils and macrophages. Here we report that encountering diverse sizes shapes undergo necrotic cell death, process associated with the formation neutrophil extracellular trap (NET)-like DNA. In receptor-interacting protein kinase (RIPK)-1 inhibition necrostatin-1s...
Serum oxalate levels suddenly increase with certain dietary exposures or ethylene glycol poisoning and are a well known cause of AKI. Established contributors to crystal-induced renal necroinflammation include the NACHT, LRR PYD domains-containing protein-3 (NLRP3) inflammasome mixed lineage kinase domain-like (MLKL) protein-dependent tubule necroptosis. These studies examined role novel form necrosis triggered by altered mitochondrial function.To better understand molecular pathophysiology...
Significance Statement Cells undergoing necrosis release extracellular high mobility group box (HMGB)-1, which triggers sterile inflammation upon AKI in mice. Neither deletion of HMGB1 from tubular epithelial cells, nor antagonism with small molecules, affects initial ischemic and immediate GFR loss unilateral ischemia/reperfusion injury (IRI). On the contrary, cell-specific deficiency, even late-onset pharmacological inhibition, increased functional structural recovery AKI, indicating that...
Abstract Background A variety of animal models has been developed for research on atherosclerosis and neointimal hyperplasia. While small contain limits translational research, we aimed to develop an model with lumen-narrowing plaques foster basic in vascular biology, the development new angioplasty devices, vessel wall imaging approaches. Methods Endothelial denudation was performed via a minimally invasive approach through auricular artery, followed by stent-retriever mediated endothelial...
Endothelial dysfunction is a central pathomechanism in diabetes-associated complications. We hypothesized pathogenic role this of cathepsin S (Cat-S), cysteine protease that degrades elastic fibers and activates the protease-activated receptor-2 (PAR2) on endothelial cells. found injection mice with recombinant Cat-S induced albuminuria glomerular cell injury PAR2-dependent manner. In vivo microscopy confirmed for intrinsic Cat-S/PAR2 ischemia-induced microvascular permeability. vitro...
Tumor necrosis factor-beta (TNF-β), as an inflammatory mediator that has been shown to promote tumorigenesis, induces NF-κB. Natural multi-targeted agent resveratrol in turn shows anti-inflammatory and anti-cancer properties. Epithelial-to-mesenchymal transition (EMT) allows cancer cells into a motile state with invasive capacities is associated metastasis development of stem (CSC). However, TNF-β-induced EMT the anti-invasion mechanism on CRC are not yet completely understood.We...
Wilson disease (WD) is characterized by a disrupted copper homeostasis resulting in dramatically increased levels, mainly liver and brain. While damage to mitochondria an established feature WD livers, much less known about such detrimental effects other organs. We therefore assessed the mitochondrial sensitivity tissue specific manner, namely of isolated rat liver, kidney, heart, brain mitochondria. Brain presented with exceptional sensitivity, as evidenced comparatively early membrane...
Natural polyphenol Calebin A has been recently discovered as a novel derivate from turmeric with anti-cancer potential. Pro-inflammatory cytokine TNF-β (lymphotoxin α) is stimulant for cancer cell malignity via activation of NF-B pathway, also in colorectal (CRC). Here, we investigated the potential to suppress TNF-β-induced signalling CRC.Three distinct CRC lines (HCT116, RKO, SW480) were treated monolayer or 3-dimensional alginate culture TNF-β, A, curcumin, BMS-345541, dithiothreitol...
Cellular plasticity is crucial for adapting to ever-changing stimuli. As a result, cells consistently reshape their translatome, and, consequently, proteome. The control of translational activity has been thoroughly examined at the stage translation initiation. However, regulation ribosome speed in widely unknown. In this study, we utilized timed runoff approach along with proteomics and transmission electron microscopy, investigate global kinetics cells. We found that speeds vary amongst...
Abstract Platelet homeostasis is essential for vascular integrity and immune defence 1,2 . Although the process of platelet formation by fragmenting megakaryocytes (MKs; thrombopoiesis) has been extensively studied, cellular molecular mechanisms required to constantly replenish pool MKs their progenitor cells (megakaryopoiesis) remains unclear 3,4 Here we use intravital imaging track dynamics megakaryopoiesis over days. We identify plasmacytoid dendritic (pDCs) as homeostatic sensors that...
Cathepsin(Cat)-S processing of the invariant chain-MHC-II complex inside antigen presenting cells is a central pathomechanism autoimmune-diseases. Additionally, Cat-S released by activated-myeloid and was recently described to activate protease-activated-receptor-(PAR)-2 in extracellular compartments. We hypothesized that blockade targets both mechanisms elicits synergistic therapeutic effects on autoimmune tissue injury. MRL-(Fas)lpr mice with spontaneous injury were treated different doses...
Abstract In crystallopathies, crystals or crystalline particles of environmental and metabolic origin deposit within tissues, induce inflammation, injury cell death eventually lead to organ-failure. The NLRP3-inflammasome is involved in mediating particles-induced but pathways leading are still unknown. Here, we have used broad range intrinsic extrinsic crystal- particle-sizes shapes, e.g. calcium phosphate, silica, titanium dioxide, cholesterol, oxalate, monosodium urate. As kidney commonly...
Although much is understood about the proinflammatory cytokine TNF-α, very limited data are available TNF-β (lymphotoxin). Whether can induce proliferation of tumor cells, how TNF-β-induced cells affected by natural products such as resveratrol and role NF-κB in this process, not understood. In present study, we used clonogenic cytotoxic methods to show effect on cell proliferation. We also examined impact TNF-β-promoted activation HCT116 colorectal cancer (CRC). Our findings showed that...
The proteasome is the main proteolytic system for targeted protein degradation in cell and fine-tuned according to cellular needs. Here, we demonstrate that mitochondrial dysfunction concomitant metabolic reprogramming of tricarboxylic acid (TCA) cycle reduce assembly activity 26S proteasome. Both mutations respiratory complex I treatment with anti-diabetic drug metformin impair activity. Defective reversible can be overcome by supplementation aspartate or pyruvate. This regulation involves...