A5044587619- Inflammasome and immune disorders
- Pancreatic function and diabetes
- Atherosclerosis and Cardiovascular Diseases
- Autophagy in Disease and Therapy
- Rheumatoid Arthritis Research and Therapies
- Calcium signaling and nucleotide metabolism
- Heme Oxygenase-1 and Carbon Monoxide
- Endoplasmic Reticulum Stress and Disease
- Adipose Tissue and Metabolism
- Microtubule and mitosis dynamics
- Bone Metabolism and Diseases
- Ubiquitin and proteasome pathways
- Immune Cell Function and Interaction
- Hair Growth and Disorders
- Bone health and treatments
- Mitochondrial Function and Pathology
- PI3K/AKT/mTOR signaling in cancer
- Adipokines, Inflammation, and Metabolic Diseases
- Aortic aneurysm repair treatments
- Cytokine Signaling Pathways and Interactions
- Erythrocyte Function and Pathophysiology
- Melanoma and MAPK Pathways
- Liver physiology and pathology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cardiac Fibrosis and Remodeling
Centre National de la Recherche Scientifique
2012-2023
Université de Strasbourg
2012-2023
Inserm
2012-2023
Institut de génétique et de biologie moléculaire et cellulaire
2012-2023
Hôpital Civil, Strasbourg
2013-2023
Institut de Biologie Moléculaire et Cellulaire
2003-2022
Laboratoire d'études sur les monothéismes
2019
Hôpitaux Universitaires de Strasbourg
2012-2013
ETH Zurich
2005-2012
Institute of Cell Biology
2012
The detailed cellular and molecular mechanisms leading to joint destruction in rheumatoid arthritis, a disease driven by proinflammatory cytokines, are still unknown. To address the question of whether osteoclasts play pivotal role this process, transgenic mice that express human TNF (hTNFtg) develop severe destructive arthritis were crossed with osteopetrotic, c-fos–deficient (c-fos–/–) completely lacking osteoclasts. resulting mutant (c-fos–/–hTNFtg) developed TNF-dependent absence All...
The detailed cellular and molecular mechanisms leading to joint destruction in rheumatoid arthritis, a disease driven by proinflammatory cytokines, are still unknown. To address the question of whether osteoclasts play pivotal role this process, transgenic mice that express human TNF (hTNFtg) develop severe destructive arthritis were crossed with osteopetrotic, c-fos–deficient (c-fos–/–) completely lacking osteoclasts. resulting mutant (c-fos–/–hTNFtg) developed TNF-dependent absence All...
The inflammasomes are multiprotein complexes sensing tissue damage and infectious agents to initiate innate immune responses. Different containing distinct sensor molecules exist. NLRP3 inflammasome is unique as it detects a variety of danger signals. It has been reported that recruited mitochondria-associated endoplasmic reticulum membranes (MAMs) activated by MAM-derived effectors. Here, we show in response activators, MAMs localize adjacent Golgi membranes. Diacylglycerol (DAG) at the...
Abstract Inflammasome complexes are pivotal in the innate immune response. The NLR family pyrin domain containing protein 3 (NLRP3) inflammasome is activated response to a broad variety of cellular stressors. However, primary and converging sensing mechanism by NLRP3 receptor initiating assembly remains ill defined. Here, we demonstrate that activators primarily converge on disruption endoplasmic reticulum–endosome membrane contact sites (EECS). This defect causes endosomal accumulation...
Apelin constitutes a novel endogenous peptide system suggested to be involved in broad range of physiological functions, including cardiovascular function, heart development, control fluid homeostasis, and obesity. is also catalytic substrate for angiotensin-converting enzyme 2, the key severe acute respiratory syndrome receptor. The vivo role still elusive. Here we report generation gene–targeted mice. mutant mice are viable fertile, appear healthy, exhibit normal body weight, water food...
In vitro studies suggest a role for c-Jun N-terminal kinases (JNKs) in proatherogenic cellular processes. We show that atherosclerosis-prone ApoE –/– mice simultaneously lacking JNK2 ( mice), but not JNK1 mice, developed less atherosclerosis than do mice. Pharmacological inhibition of JNK activity efficiently reduced plaque formation. Macrophages displayed suppressed foam cell formation caused by defective uptake and degradation modified lipoproteins showed increased amounts the...
Dysfunction and loss of insulin-producing pancreatic β cells represent hallmarks diabetes mellitus. Here, we show that mice lacking the mitogen-activated protein kinase (MAPK) p38δ display improved glucose tolerance due to enhanced insulin secretion from cells. Deletion results in pronounced activation D (PKD), latter which have identified as a pivotal regulator stimulated exocytosis. catalyzes an inhibitory phosphorylation PKD1, thereby attenuating secretion. In addition, null are protected...
The AP-1 transcription factor c-Jun is a key regulator of hepatocyte proliferation. Mice lacking in the liver (c-jun (Deltali*)) display impaired regeneration after partial hepatectomy (PH). This phenotype correlates with increased protein levels cdk-inhibitor p21 liver. We performed PH experiments several double-knockout mouse models to genetically identify signaling events regulated by c-Jun. Inactivation p53 c-jun (Deltali*) mice abrogated both cell cycle block and expression....
Too hungry to eat, too not eat Pancreatic beta cells, the source of insulin in response food, employ an unusual mechanism adapt nutrient depletion. Goginashvili et al. found that starvation cells induced selective degradation newly formed granules through their fusion with lysosomes, cell's garbage disposal units (see Perspective by Rutter). The sensor mTOR is recruited these leading its local activation and suppression autophagy—a process which “eat” own constituents. Protein kinase D, a...
Abstract NLRP3 controls the secretion of inflammatory cytokines IL-1β/18 and pyroptosis by assembling inflammasome. Upon coordinated priming activation stimuli, recruits NEK7 within hetero-oligomers that nucleate ASC caspase-1 filaments, but apical molecular mechanisms underlying inflammasome assembly remain elusive. Here we show recruitment to is controlled phosphorylation status S803 located interaction surface, in which phosphorylated upon later dephosphorylated activation. Phosphomimetic...
Separase is a protease whose liberation from its inhibitory chaperone Securin triggers sister chromatid disjunction at anaphase onset in yeast by cleaving cohesin's kleisin subunit. We have created conditional knockout alleles of the mouse and genes. Deletion both copies but not causes embryonic lethality. Loss reduces activity because deletion just one copy gene lethal to embryos lacking Securin. In fibroblasts, depletion blocks separation does prevent other aspects mitosis, cytokinesis, or...
Despite their role in resolving inflammatory insults, neutrophils trigger inflammation-induced acute lung injury (ALI), culminating respiratory distress syndrome (ARDS), a frequent complication with high mortality humans. Molecular mechanisms underlying recruitment of to sites inflammation remain poorly understood. Here, we show that p38 MAP kinase p38δ is required for into sites. Global and myeloid-restricted deletion mice results decreased alveolar neutrophil accumulation attenuation ALI....