A5021128098- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- High Altitude and Hypoxia
- Metabolomics and Mass Spectrometry Studies
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- Mitochondrial Function and Pathology
- Renal cell carcinoma treatment
- Renal and related cancers
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- 14-3-3 protein interactions
- Hemoglobin structure and function
- Gene expression and cancer classification
- Fibroblast Growth Factor Research
- Erythrocyte Function and Pathophysiology
- Connective Tissue Growth Factor Research
- Molecular Biology Techniques and Applications
- Heme Oxygenase-1 and Carbon Monoxide
- Cancer-related Molecular Pathways
- Respiratory Support and Mechanisms
- Chronic Kidney Disease and Diabetes
- Psoriasis: Treatment and Pathogenesis
- Neonatal Respiratory Health Research
Novartis (Switzerland)
2013-2024
University of Zurich
2006-2023
Novartis Institutes for BioMedical Research
2013-2017
Swiss Integrative Center for Human Health
2005-2016
Czech Academy of Sciences, Institute of Physiology
2005-2011
University Medical Center Freiburg
2011
University of Duisburg-Essen
2011
Genomics (United Kingdom)
2011
Swiss Insurance Association
2010
University of Lübeck
2002-2008
Hypoxia-inducible factors (HIF) are a family of heterodimeric transcriptional regulators that play pivotal roles in the regulation cellular utilization oxygen and glucose essential angiogenesis solid tumor ischemic disorders. The transactivation activity HIF complexes requires recruitment p300/CREB-binding protein (CBP) by HIF-1α HIF-2α undergo oxygen-dependent degradation. activation tumors is caused several including mitogen-activated kinase (MAPK) signaling. Here we investigated molecular...
Hypoxia‐inducible factor 1 (HIF‐1) is a heterodimeric DNA‐binding complex of the subunits α and β with relevance in O 2 energy homeostasis. The labile component, HIF‐1α, not only activated by hypoxia but also peptides such as insulin interleukin‐1 (IL‐1) normoxia. We investigated whether inhibitors mitogen‐activated protein kinase kinases (MAPKKs: PD 98059, U0126) phosphatidylinositol 3‐kinase (PI3K: LY 294002) do lower hypoxia‐induced, insulin‐ IL‐1‐induced HIF‐1α accumulation HIF‐1 human...
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...
The HIFs (hypoxia-inducible factors) are a family of heterodimeric transcription factors essential for the adaptation cells to reduced oxygen supply. Three human PHDs (prolyl hydroxylase domain proteins, PHD1–PHD3) initiate oxygen-dependent degradation HIF-α-subunits in normoxia. RNA interference directed against PHD2, but not PHD1 or PHD3, is sufficient stabilize HIF-1α Therefore PHD2 regarded as main cellular sensor. itself up-regulated by hypoxia and may thus limit hypoxic signalling. By...
Voretigene neparvovec (VN) is the first available gene therapy for patients with biallelic RPE65-mediated inherited retinal dystrophy who have sufficient viable cells. PERCEIVE an ongoing, post-authorization, prospective, multicenter, registry-based observational study and largest assessing real-world, long-term safety effectiveness of VN. Here, we present outcomes 103 treated VN according to local prescribing information. The mean (SD) age was 19.5 (10.85) years, 52 (50.5%) were female,...
The heterodimeric hypoxia-inducible transcription factors (HIFs) are central regulators of the response to low oxygenation. HIF-α subunits constitutively expressed but rapidly degraded under normoxic conditions. Oxygen-dependent hydroxylation two conserved prolyl residues by prolyl-4-hydroxylase domain-containing enzymes (PHDs) targets for proteasomal destruction. We identified peptidyl cis/trans isomerase FK506-binding protein 38 (FKBP38) as a novel interactor PHD2. Yeast two-hybrid,...
Abstract p300/cyclic AMP–responsive element binding protein–binding protein (CBP) are general coactivators for multiple transcription factors involved in various cellular processes. Several highly conserved domains of p300/CBP serve as interacting sites and regulatory proteins. Particularly, the intrinsic histone acetyltransferase (HAT) activity transactivation (TAD) play essential roles their coactivating function. Autoacetylation is commonly observed cell-free HAT assays has been...
Tumor hypoxia and the hypoxia-inducible factors (HIFs) play a central role in development of cancer. To study relationship between tumor growth, hypoxia, stabilization HIF-1α, HIF transcriptional activity, we have established an vivo imaging tool that allows longitudinal noninvasive monitoring these processes mouse C51 allograft model. We used positron emission tomography (PET) with hypoxia-sensitive tracer [ 18 F]-fluoromisonidazole (FMISO) to measure over 14 days. Stabilization HIF-1α...
The identification of cell surface accessible biomarkers enabling diagnosis, disease monitoring, and treatment renal carcinoma (RCC) is as challenging the biology progression RCC unpredictable.A hallmark most loss-of-function von Hippel-Lindau (pVHL) protein by mutation its gene (VHL).Using capturing (CSC) technology, we screened identified N-glycoproteins in pVHL-negative positive 786-O cells.One hundred six were identified.Stable isotope labeling with amino acids culture-based...
Recently, immunohistochemical analysis of myoglobin (MB) in human breast cancer specimens has revealed a surprisingly widespread expression MB this nonmuscle context. The positive correlation with hypoxia-inducible factor 2α (HIF-2α) and carbonic anhydrase IX suggested that oxygen regulates carcinomas. Here, we report mRNA protein levels are robustly induced by prolonged hypoxia cell lines, part via HIF-1/2-dependent transactivation. hypoxia-induced originated from novel alternative...
Abstract Antibodies targeting IL-17A or its receptor IL-17RA show unprecedented efficacy in the treatment of autoimmune diseases such as psoriasis. These therapies, by neutralizing critical mediators immunity, may increase susceptibility to infections. Here, we compared effect antibodies IL-17A, IL-17F TNFα on murine host responses Mycobacterium tuberculosis infection evaluating lung transcriptomic, microbiological and histological analyses. Coinciding with a significant mycobacterial burden...
Abstract The histone variant 2AX (H2AX) is phosphorylated at Serine 139 by the PI3K-like kinase family members ATM, ATR and DNA-PK. Genotoxic stress, such as tumor radio- chemotherapy, considered to be main inducer of H2AX (γH2AX), which forms distinct foci sites DNA damage where repair factors accumulate. γH2AX accumulation under severe hypoxic/anoxic (0.02% oxygen) conditions has recently been reported follow replication fork stalling in absence detectable damage. In this study, we found...
A mismatch between metabolic demand and oxygen delivery leads to microenvironmental changes in solid tumors. The resulting tumor hypoxia is associated with malignant progression, therapy resistance poor prognosis. However, the molecular mechanisms underlying hypoxic tumors are not fully understood. hypoxia-inducible factor (HIF) a master transcriptional activator of oxygen-regulated gene expression. Transformed mouse embryonic fibroblasts (MEFs) derived from HIF-1alpha-deficient mice popular...
The human prolyl-4-hydroxylase domain (PHD) proteins 1–3 are known as cellular oxygen sensors, acting via the degradation of hypoxia-inducible factor (HIF) α-subunits. PHD2 and PHD3 genes inducible by HIFs themselves, suggesting a negative feedback loop that involves PHD abundance. To identify novel regulators gene, an expression array 704 transcription factors was screened method allows distinguishing between HIF-dependent HIF-independent promoter regulation. Among others, E-twenty six ETS...