A5060831877- Genetics and Neurodevelopmental Disorders
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- Immune cells in cancer
- Peroxisome Proliferator-Activated Receptors
- Adenosine and Purinergic Signaling
- Cytomegalovirus and herpesvirus research
- CRISPR and Genetic Engineering
- Autophagy in Disease and Therapy
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- HIV Research and Treatment
- Mitochondrial Function and Pathology
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Ferroptosis and cancer prognosis
- Mast cells and histamine
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Bone Metabolism and Diseases
- Inflammasome and immune disorders
- Virus-based gene therapy research
- Cholesterol and Lipid Metabolism
- Lipid metabolism and biosynthesis
- Extracellular vesicles in disease
- Histone Deacetylase Inhibitors Research
ETH Zurich
2015-2025
Ludwig Cancer Research
2024
University of Lausanne
2024
Matsumoto Dental University
2020-2023
Max Planck Institute of Immunobiology and Epigenetics
2018-2022
Kobe University
2008-2009
The selenoenzyme glutathione peroxidase 4 (Gpx4) is a major scavenger of phospholipid hydroperoxides. Although Gpx4 represents key component the reactive oxygen species-scavenging network, its relevance in immune system yet to be defined. Here, we investigated importance for physiological T cell responses by using cell-specific Gpx4-deficient mice. Our results revealed that, despite normal thymic development, CD8(+) cells from T(ΔGpx4/ΔGpx4) mice had an intrinsic defect maintaining...
How cells adapt metabolism to meet demands is an active area of interest across biology. Among a broad range functions, the polyamine spermidine needed hypusinate translation factor eukaryotic initiation 5A (eIF5A). We show here that hypusinated eIF5A (eIF5AH) promotes efficient expression subset mitochondrial proteins involved in TCA cycle and oxidative phosphorylation (OXPHOS). Several these have targeting sequences (MTSs) part confer increased dependency on eIF5AH. In macrophages,...
Competition for nutrients like glucose can metabolically restrict T cells and contribute to their hyporesponsiveness during cancer. Metabolic adaptation the surrounding microenvironment is therefore key maintaining appropriate cell function. For instance, cancer use acetate as a substrate alternative fuel metabolism growth. Here, we show that rescues effector function in glucose-restricted CD8+ cells. Mechanistically, promotes histone acetylation chromatin accessibility enhances IFN-γ gene...
Abstract Foamy macrophages, which have prominent lipid droplets (LDs), are found in a variety of disease states. Toll-like receptor agonists drive triacylglycerol (TG)-rich LD development macrophages. Here we explore the basis and significance this process. Our findings indicate that is result metabolic commitment to TG synthesis on background decreased fatty acid oxidation. essential for optimal inflammatory macrophage activation as its inhibition, prevents development, has marked effects...
Prime editing is a highly versatile CRISPR-based genome technology that works without DNA double-strand break formation. Despite rapid technological advances, in vivo application for the treatment of genetic diseases remains challenging. Here, we developed size-reduced Sp Cas9 prime editor (PE) lacking RNaseH domain (PE2 Δ RnH ) and an intein-split construct p.1153) adeno-associated virus–mediated delivery into liver. Editing efficiencies reached 15% at Dnmt1 locus were further elevated to...
Abstract The thioredoxin-1 (Trx1) system is an important contributor to cellular redox balance and a sensor of energy glucose metabolism. Here we show critical c-Myc-dependent activation the Trx1 during thymocyte peripheral T-cell proliferation, but repression quiescence. Deletion thioredoxin reductase-1 ( Txnrd1 ) prevents expansion CD4 − CD8 population, whereas deletion in + thymocytes does not affect further maturation homeostasis αβT cells. However, for activated population viral...
Environmental microbial triggers shape the development and functionality of immune system. Alveolar macrophages (AMs), tissue-resident lungs, are in constant direct contact with inhaled particles microbes. Such exposures likely impact AM reactivity to subsequent challenges by immunological imprinting mechanisms referred as trained immunity. Here, we investigated whether a ubiquitous compound has potential induce training vivo. We discovered that intranasal exposure ambient amounts...
Acumulation of oxidized membrane lipids ultimately results in ferroptotic cell death, which can be prevented by the selenoenzyme glutathione peroxidase 4 (Gpx4). In vivo conditions promoting ferroptosis and susceptible types are still poorly defined. this study, we analyzed conditional deletion Gpx4 mice specifically myeloid lineages. Surprisingly, development maintenance LysM+ macrophages neutrophils, as well CD11c+ monocyte-derived dendritic cells were unaffected absence Gpx4....
Abstract Antioxidant systems maintain cellular redox (oxidation-reduction) homeostasis. In contrast with other key pathways, such as the thioredoxin system, glutathione, and NF-E2-related factor 2 (Nrf2), little is known about function of redox-sensitive organelle “peroxisome” in immune cells. this study, we show that absence peroxisomes conditional Pex5-deficient mice strikingly results impaired homeostatic maintenance innate-like B cells, namely, B1 marginal zone which translates into a...
Abstract Bone tissues have trabecular bone with a high turnover and cortical low turnover. The mechanisms by which the rate of these is determined remain unclear. Osteocytes secrete sclerostin, Wnt/β-catenin signaling antagonist, inhibit formation. We found that sclerostin expression in more marked than Sost reporter mice. Leukemia inhibitory factor (LIF) secreted from osteoclasts reportedly suppressed promoted Here, we report downregulate promote Treatment C57BL/6 mice an anti-RANKL...
We have previously shown that WW domain-containing oxidoreductase (WWOX) has tumour-suppressing effects and its expression is frequently reduced in pancreatic carcinoma. In this study, we examined WWOX intraductal papillary mucinous neoplasm of the pancreas (IPMN) to assess function duct tumourigenesis using immunohistochemistry methylation-specific polymerase chain reaction analysis. Among 41 IPMNs including adenomas (IPMAs) carcinomas (IPMCs), loss or immunoreactivity was detected 3 (15%)...
Abstract Cancer-associated fibroblasts (CAF) are key regulators of tumorigenesis. Further insights into the tumor-promoting mechanisms action CAFs could help improve cancer diagnosis and treatment. Here we show that formin mDia2 regulates positioning function mitochondria in dermal fibroblasts, thereby promoting a protumorigenic CAF phenotype. Mechanistically, stabilized mitochondrial trafficking protein MIRO1. Loss or MIRO1 reduced presence ATP levels near plasma membrane at CAF-tumor cell...
Severe periodontitis causes alveolar bone resorption, resulting in tooth loss. Developments of tissue regeneration therapy that can restore mass are desired for periodontal disease. The application morphogenetic protein-2 (BMP-2) has been attempted fractures and severe BMP-2 reportedly induces sclerostin expression, an inhibitor Wnt signals, attenuates acquisition. However, the effect sclerostin-deficiency on BMP-2-induced not fully elucidated. We investigated ectopic bones Sost-knockout...
Abstract Prime editing is a versatile genome technology that does not rely on DNA double-strand break formation and homology-directed repair (HDR). This makes it promising tool for correcting pathogenic mutations in tissues consisting predominantly of postmitotic cells, such as the liver. While recent studies have already demonstrated proof-of-concept vivo prime editing, use viral delivery vectors resulted prolonged editor (PE) expression, posing challenges clinical application. Here, we...
Macrophages are integral to most tissues. Foam cells, macrophages with lipid droplets (LDs) which stores of triacylglycerols (TGs) and cholesterol esters (CEs), found in various disease states 1 . LDs can act as energy since TG lipolysis releases fatty acids (FAs) for mitochondrial oxidation (FAO), a process that relies on long-chain FA conversion into acylcarnitines by the enzyme Cpt1a 2 However, macrophages, proinflammatory signals result diminished FAO increased synthesis LD development...