- Cancer, Hypoxia, and Metabolism
- Metabolomics and Mass Spectrometry Studies
- Nasal Surgery and Airway Studies
- Metabolism, Diabetes, and Cancer
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Hemoglobin structure and function
- High Altitude and Hypoxia
- Developmental Biology and Gene Regulation
- Autophagy in Disease and Therapy
- Sinusitis and nasal conditions
- RNA Research and Splicing
- Cellular transport and secretion
- Plant nutrient uptake and metabolism
- Renal and related cancers
- Head and Neck Surgical Oncology
- Diagnosis and treatment of tuberculosis
- Extracellular vesicles in disease
- Photosynthetic Processes and Mechanisms
- Inflammasome and immune disorders
- Infectious Diseases and Tuberculosis
- Immune cells in cancer
- Mycobacterium research and diagnosis
- Fungal and yeast genetics research
- Silk-based biomaterials and applications
University of Zurich
2009-2022
Swiss Integrative Center for Human Health
2006-2021
RELX Group (United States)
2019
Institute for Postgraduate Medical Education
2018
Auckland City Hospital
2013
Greenlane Clinical Centre
2013
University Hospital of Zurich
2004-2011
Raigmore Hospital
2007-2011
Western General Hospital
2008
Czech Academy of Sciences, Institute of Physiology
2007
Hypoxia regulates autophagy and nucleotide-binding oligomerization domain receptor, pyrin containing (NLRP)3, two innate immune mechanisms linked by mutual regulation associated to IBD. Here we show that hypoxia ameliorates inflammation during the development of colitis modulating mammalian target rapamycin (mTOR)/NLRP3 pathway. significantly reduces tumor necrosis factor α, interleukin (IL)-6 NLRP3 expression, increases turnover protein p62 in colon biopsies Crohn's disease patients,...
Prolyl 4-hydroxylase domain (PHD) proteins are oxygen-dependent enzymes that hydroxylate hypoxia-inducible transcription factor (HIF) alpha-subunits, leading to their subsequent ubiquitination and degradation. Paradoxically, the expression of two family members (PHD2 PHD3) is induced in hypoxic cell culture despite reduced availability oxygen co-substrate, it has been suggested they become functionally relevant following re-oxygenation rapidly terminate HIF response. Here we show PHDs also...
ObjectivesThe core of advanced atherosclerotic plaques turns hypoxic as the arterial wall thickens and oxygen diffusion capacity becomes impaired. Macrophage-derived foam cells play a pivotal role in plaque formation by expressing scavenger receptors that regulate lipid uptake. However, hypoxia receptor regulation remains incompletely understood.Methods resultsUsing RT-qPCR, flow cytometry immunoblotting, we found mRNA protein expression levels A (SRA) cluster differentiation 36 (CD36) were...
The asparagine hydroxylase, factor inhibiting HIF (FIH), confers oxygen-dependence upon the hypoxia-inducible (HIF), a master regulator of cellular adaptive response to hypoxia. Studies investigating whether hydroxylation is general regulatory oxygen-dependent modification have identified multiple non-HIF targets for FIH. However, functional consequences this outside pathway remain unclear. Here, we demonstrate that deubiquitinase ovarian tumor domain containing ubiquitin aldehyde binding...
Avian embryos and neonates acquire passive immunity by transferring maternal immunoglobulins from serum to egg yolk. Despite being a convenient source of antibodies, yolk (IgY) immunized hens have so far received scant attention in research. Here we report the generation rapid isolation IgY against α subunit human hypoxia-inducible factor 1 (HIF-1α). Anti-HIF-1α antibodies were affinity purified tested for their performance various applications. Abundant HIF-1α protein was detected Western...
While it is well-established that distal hypoxia response elements (HREs) regulate hypoxia-inducible factor (HIF) target genes such as erythropoietin (Epo), an interplay between multiple and proximal (promoter) HREs has not been described so far. Hepatic Epo expression regulated by a HRE located downstream of the EPO gene, but this 3' dispensable for renal gene expression. We previously identified 5' could show both direct exogenous reporter Here, we whereas in hepatic cells required,...
Abstract Aim Fibroblast‐like renal erythropoietin (Epo) producing (REP) cells of the corticomedullary border region “sense” a decrease in blood oxygen content following anaemia or hypoxaemia. Burst‐like transcription Epo during tissue hypoxia is transient and lost fibrotic remodelling, as observed chronic kidney disease. The reason for this loss expression under debate. Therefore, we tested hypothesis that REP cell migration, and/or differentiation may cause inhibition. Methods Using...
Cellular oxygen is sensed by prolyl-4-hydroxylase domain (PHD) proteins that hydroxylate hypoxia-inducible factor (HIF) α subunits. Under normoxic conditions, hydroxylated HIFα bound the von Hippel–Lindau (pVHL) tumor suppressor, leading to ubiquitinylation and proteasomal degradation. hypoxic hydroxylation becomes reduced, stabilization. The authors recently showed changes in PHD abundance activity can regulate stability under as well conditions. Thus, sensors themselves represent effectors...
// Kamila Müller-Edenborn 1,2,* , Karolin Léger 2,3,* Jesus F. Glaus Garzon Carole Oertli 1,2 Ali Mirsaidi 2,4 Peter J. Richards Hubert Rehrauer 5 Patrick Spielmann David Hoogewijs Lubor Borsig Michael O. Hottiger and Roland H. Wenger 1 Institute of Physiology, University Zurich, Switzerland 2 Zurich Center for Integrative Human Physiology (ZIHP), 3 Veterinary Biochemistry Molecular Biology, 4 Applied Biotechnology Medicine, Functional Genomics Center, * The authors have...
The ubiquitously expressed hypoxia‐inducible factor‐1 (HIF‐1) is involved in expression of a large number oxygen‐regulated genes. HIF‐1 heterodimer consisting an α and β subunit, both belonging to the basic‐helix‐loop‐helix Per‐aryl hydrocarbon receptor nuclear translocator‐Sim (PAS) family transcription factors. Whereas HIF‐1α novel member this family, HIF‐1β identical aryl translocator, previously recognized be xenobiotic metabolism. cDNA cloning revealed that mouse can as two mRNA...
PASKIN links energy flux and protein synthesis in yeast, regulates glycogen mammals, has been implicated glucose-stimulated insulin production pancreatic β-cells. Using newly generated monoclonal antibodies, was localized the nuclei of human testis germ cells midpiece sperm tails. A speckle-like nuclear pattern observed for endogenous HeLa addition to its cytoplasmic localization. By yeast two-hybrid screening, we identified multifunctional eukaryotic translation elongation factor eEF1A1 as...
Protein:protein interactions are the basis of molecular communication and usually transient non-covalent nature, while covalent other than ubiquitination rare. For cellular adaptations, oxygen peroxide sensor factor inhibiting HIF (FIH) confers oxidant stress sensitivity to hypoxia inducible (HIF) by asparagine hydroxylation. We investigated whether FIH contributes adaptation also through mechanisms identified a sensitive, likely covalent, bond formation with several client proteins,...
Juvenile nasopharyngeal angiofibroma is a rare, benign tumor that occurs most often in adolescent males. Common practice to excise the with open or endoscopic surgery. We report case of 17-year-old male who presented 1995 mass filling left posterior nasal cavity. A diagnosis juvenile was obtained computed tomography and magnetic resonance imaging. The patient elected have no treatment. On annual scans, lesion changed little until 1998, when it began gradually decrease size. Although not well...
Phthalocyanines (Pcs) are promising candidates for photodynamic therapy (PDT) due to their absorption in the phototherapeutic window. However, highly aromatic Pc core leads undesired aggregation and decreased reactive oxygen species (ROS) production. Therefore, short PEG chain functionalized A3B type asymmetric photosensitizers (PSs) were designed order decrease increase aqueous solubility. Here we report synthesis, characterization, optical properties, cellular localization, cytotoxicity of...