A5088143377- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Renal and related cancers
- Lipid metabolism and biosynthesis
- Genetic Syndromes and Imprinting
- Cholesterol and Lipid Metabolism
- Metabolism, Diabetes, and Cancer
- Metabolomics and Mass Spectrometry Studies
- Epigenetics and DNA Methylation
- PI3K/AKT/mTOR signaling in cancer
- Ion Transport and Channel Regulation
- Ubiquitin and proteasome pathways
- Reproductive Biology and Fertility
- RNA modifications and cancer
- Prostate Cancer Treatment and Research
- Bacteriophages and microbial interactions
- Mitochondrial Function and Pathology
- Peroxisome Proliferator-Activated Receptors
- Zebrafish Biomedical Research Applications
- Caveolin-1 and cellular processes
- RNA Research and Splicing
- Pluripotent Stem Cells Research
- Cancer Genomics and Diagnostics
- RNA and protein synthesis mechanisms
- Molecular Biology Techniques and Applications
German Cancer Research Center
2019-2025
Heidelberg University
2019-2025
DKFZ-ZMBH Alliance
2024
European Molecular Biology Laboratory
2022
Max Planck Institute of Biophysics
2022
European Molecular Biology Laboratory
2022
European Molecular Biology Laboratory
2017-2021
University of Würzburg
2019-2021
European Molecular Biology Organization
2014
University of Oslo
2009
Abstract Increased glycolytic flux is a hallmark of cancer; however, an increasing body evidence indicates that ATP production may be dispensable in cancer, as metabolic plasticity allows cancer cells to readily adapt disruption glycolysis by via oxidative phosphorylation. Using functional genomic screening, we show here liver unique sensitivity toward aldolase A (ALDOA) depletion. Targeting disrupting the catalytic activity ALDOA led severe energy stress and cell cycle arrest murine human...
How metabolism is rewired during embryonic development still largely unknown, as it remains a major technical challenge to resolve metabolic activities or metabolite levels with spatiotemporal resolution. Here, we investigated changes of organogenesis-stage mouse embryos, focusing on the presomitic mesoderm (PSM). We measured glycolytic labeling kinetics from 13C-glucose tracing experiments and detected elevated glycolysis in posterior, more undifferentiated PSM. found evidence that spatial...
Abstract Prostate cancer (PCa) shows strong dependence on the androgen receptor (AR) pathway. Here, we show that squalene epoxidase (SQLE), an enzyme of cholesterol biosynthesis pathway, is overexpressed in advanced PCa and its expression correlates with poor survival. SQLE controlled by micro-RNA 205 (miR-205), which significantly downregulated PCa. Restoration miR-205 or competitive inhibition led to de novo biosynthesis. Furthermore, was essential for proliferation AR-positive cell lines,...
Abstract Energetic stress compels cells to evolve adaptive mechanisms adjust their metabolism. Inhibition of mTOR kinase complex 1 (mTORC1) is essential for cell survival during glucose starvation. How mTORC1 controls viability starvation not well understood. Here we show that the effectors eukaryotic initiation factor 4E binding proteins 1/2 (4EBP1/2) confer protection mammalian and budding yeast under Mechanistically, 4EBP1/2 promote NADPH homeostasis by preventing NADPH-consuming fatty...
Metabolic reprogramming is critical during clear cell renal carcinoma (ccRCC) tumorigenesis, manifested by accumulation of lipid droplets (LDs), organelles that have emerged as new hallmarks cancer. Yet, regulation their biogenesis still poorly understood. Here, we demonstrate MYC inhibition in ccRCC cells lacking the von Hippel Lindau ( VHL ) gene leads to increased triglyceride content potentiating LD formation a glutamine-dependent manner. Importantly, concurrent signaling and glutamine...
How cellular metabolic state impacts programs is a fundamental, unresolved question. Here, we investigated how glycolytic flux embryonic development, using presomitic mesoderm (PSM) patterning as the experimental model. First, identified fructose 1,6-bisphosphate (FBP) an in vivo sentinel metabolite that mirrors within PSM cells of post-implantation mouse embryos. We found medium-supplementation with FBP, but not other metabolites, such 6-phosphate and 3-phosphoglycerate, impaired...
Many metabolic pathways, including lipid metabolism, are rewired in tumors to support energy and biomass production allow adaptation stressful environments. Neuroblastoma is the second deadliest solid tumor children. Genetic aberrations, as amplification of MYCN-oncogene, correlate strongly with disease progression. Yet, there only a few molecular targets successfully exploited clinic. Here we show that inhibition fatty acid synthesis led increased neural differentiation reduced burden...
Cellular growth is a fundamental process of life and must be precisely controlled in multicellular organisms. Growth crucially by the number functional ribosomes available cells. The production new depends critically on activity RNA polymerase (RNAP) II addition to RNAP I III, which produce ribosomal RNAs. Indeed, expression both, proteins required for ribosome assembly (ribosomal biogenesis factors), considered rate-limiting synthesis. Here, we used genetic screening identify novel...
Metabolism has emerged as a key factor in homeostasis and disease including cancer. Yet, little is known about the heterogeneity of metabolic activity cancer cells due to lack tools directly probe it. Here, we present novel method,
Abstract Despite the continued success of advanced cancer therapies, hepatocellular carcinoma (HCC) represents a substantial challenge to current treatment modalities that are not sufficiently effective for management disease. Metabolic reprogramming is hallmark and many oncogenic signaling pathways impact on cellular metabolism. Here, we investigating changes in metabolism different oncogene-driven mouse models liver identify selective metabolic vulnerabilities associated with HCC could be...
Background Embryonic development is not regulated solely by genetic programs but also metabolic state and environmental cues, which can impact on gene function. Metabolism influence function both canonically (providing substrates for posttranslational modifications etc.) non-canonically example via moonlighting enzymes. Moonlighting enzymes have functions in addition to their known catalytic one. They are widespread among involved sugar metabolism. For example, 7 out of the 10 glycolysis...
SUMMARY Energetic stress compels cells to evolve adaptive mechanisms maintain homeostasis. Here, we report that the negative regulators of mRNA translation initiation eukaryotic factor 4E binding proteins 1/2 (4EBP1/2) are essential promote survival mammalian and budding yeast under glucose starvation. Functionally, 4EBP1/2 inhibit fatty acid synthesis upon energetic via repression Acetyl-CoA Carboxylase Alpha ( ACACA ) translation, sparing NADPH, intracellular redox balance. This has...
Abstract Despite advances in the treatment of breast cancer, it is still second leading cause cancer-related death women worldwide. A large number patients develop recurrence and die advanced metastatic disease. More than 70% cancers (mBC) express androgen receptor (AR) representing a potential target for anti-hormone therapies. AR suggested to directly interact with an associated transcription factor (ARaTF) however functional role ARaTF its interaction remains be elucidated. We find that...