A5007134273- Metabolism and Genetic Disorders
- Folate and B Vitamins Research
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Neonatal Health and Biochemistry
- Cancer-related gene regulation
- Eosinophilic Esophagitis
- Mitochondrial Function and Pathology
- Metabolomics and Mass Spectrometry Studies
- Lysosomal Storage Disorders Research
- Drug Transport and Resistance Mechanisms
- Porphyrin Metabolism and Disorders
- Cancer, Hypoxia, and Metabolism
- Immune cells in cancer
- Lung Cancer Research Studies
- Lipid metabolism and disorders
- HIV/AIDS drug development and treatment
- Polyamine Metabolism and Applications
- Immune Response and Inflammation
- Advanced Glycation End Products research
- Diabetic Foot Ulcer Assessment and Management
- Wound Healing and Treatments
- HIV Research and Treatment
- Immune Cell Function and Interaction
- Adipose Tissue and Metabolism
Heidelberg University
2017-2024
Heidelberg University
2024
University Hospital Heidelberg
2017-2020
University of Zurich
2015-2019
University Children's Hospital Zurich
2013-2019
Swiss Integrative Center for Human Health
2015
Boston Children's Hospital
2014
Johannes Gutenberg University Mainz
1995
Alveolar macrophages (AM) are critical for defense against bacterial and fungal infections. However, a definitive role of AM in viral infections remains unclear. We here report that play key survival to influenza vaccinia virus infection by maintaining lung function thereby protecting from asphyxiation. Absence GM-CSF-deficient (Csf2−/−) mice or selective depletion wild-type resulted impaired gas exchange fatal hypoxia associated with severe morbidity infection, while clearance was affected...
The fatty acid mixture of human milk is ideal for the newborn but little known about its composition in first few weeks lactation. Of special interest are levels long-chain PUFAs (LCPUFAs), since these essential newborn's development. Additionally, LCPUFAs arachidonic (AA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) precursors lipid mediators which regulate inflammation.We determined 94 samples from 30 mothers over month lactation acids using GC-MS quantified HPLC-MS/MS.Over four...
Glioblastoma is a deadly brain tumor for which there no cure. The presence of glioblastoma stem-like cells (GSCs) contributes to the heterogeneous nature disease and makes developing effective therapies challenging. have been shown influence their environment by releasing biological nanostructures known as extracellular vesicles (EVs). Here, we investigated role GSC-derived nanosized EVs (<200 nm) in heterogeneity, plasticity, aggressiveness, with particular focus on protein, metabolite,...
Cell metabolism reprogramming to sustain energy production, while reducing oxygen and consuming processes is crucially important for the adaptation hypoxia/ischemia. Adaptive metabolic rewiring controlled by hypoxia-inducible factors (HIFs). Accumulating experimental evidence indicates that timely activation of HIF in brain-resident cells improves outcome from acute ischemic stroke. However, underlying molecular mechanisms are still incompletely understood. Thus, we investigated whether...
Background and aims Increased propionylcarnitine levels in newborn screening are indicative for a group of potentially severe disorders including propionic acidemia (PA), methylmalonic acidemias combined remethylation (MMACBL). This alteration is relatively non-specific, resulting the necessity confirmation differential diagnosis subsequent tests. Thus, we aimed to develop multiplex approach concurrent determination 3-hydroxypropionic acid, acid methylcitric from same dried blood spot (DBS)...
The gene encoding for Epstein-Barr virus-induced G-protein-coupled receptor 2 (EBI2) is a risk inflammatory bowel disease (IBD). Together with its oxysterol ligand 7α,25-dihydroxycholesterol, EBI2 mediates migration and differentiation of immune cells. However, the role in colonic system remains insufficiently studied. We found increased mRNA expression oxysterol-synthesizing enzymes (CH25H, CYP7B1) inflamed colon patients ulcerative colitis mice acute or chronic dextran sulfate sodium (DSS)...
We report the first well-characterized selective chemical probe for histone deacetylase 10 (HDAC10) with unprecedented selectivity over other HDAC isozymes. HDAC10 deacetylates polyamines and has a distinct substrate specificity, making it unique among 11 zinc-dependent hydrolases. Taking inspiration from polyamine substrates, we systematically inserted an amino group ("aza-scan") into hexyl linker moiety of approved drug Vorinostat (SAHA). This one-atom replacement (C→N) transformed SAHA...
Abstract The malate shuttle is traditionally understood to maintain NAD + /NADH balance between the cytosol and mitochondria. Whether has additional functions unclear. Here we show that chronic viral infections induce CD8 T cell expression of GOT1, a central enzyme in shuttle. Got1 deficiency decreased ratio limited antiviral responses infection; however, increasing did not restore responses. reduced production ammonia scavenger 2-ketoglutarate (2-KG) from glutaminolysis led toxic...
Background and aims Inborn errors of purine pyrimidine metabolism are a diverse group disorders with possible serious or life-threatening symptoms. They may be associated neurological symptoms, renal stone disease immunodeficiency. However, the clinical presentation can nonspecific mild so that number cases missed. Previously published assays lacked detection certain diagnostically important biomarkers, including SAICAr, AICAr, beta-ureidoisobutyric acid, 2,8-dihydroxyadenine orotidine,...
Cytosolic histone deacetylase-10 (HDAC10) specifically deacetylates the modified polyamine N
Abstract Small cell lung cancer (SCLC) patients frequently experience a remarkable response to first-line therapy. Follow up maintenance treatments aim control residual tumor cells, but generally fail due cross-resistance, inefficient targeting of vulnerabilities, or dose-limiting toxicity, resulting in relapse and disease progression. Here, we show that SCLC similar their cells origin, pulmonary neuroendocrine (PNECs), exhibit low activity pathways protecting against reactive oxygen species...
We report the first selective chemical probes for histone deacetylase 10 (HDAC10) with unprecedented selectivity over other HDAC isozymes. HDAC10 deacetylates polyamines and has a distinct substrate specificity, making it unique among 11 zinc-dependent hydrolases. Taking inspiration from polyamine substrates, we systematically inserted an amino group (“aza-scan”) into hexyl linker moiety of approved drug Vorinostat (SAHA). This one atom replacement (C-->N) transformed SAHA unselective...
We report the first well-characterized selective chemical probe for histone deacetylase 10 (HDAC10) with unprecedented selectivity over other HDAC isozymes. HDAC10 deacetylates polyamines and has a distinct substrate specificity, making it unique among 11 zinc-dependent hydrolases. Taking inspiration from polyamine substrates, we systematically inserted an amino group (“aza-scan”) into hexyl linker moiety of approved drug Vorinostat (SAHA). This one atom replacement (C-->N) transformed...
Abstract The gene encoding for Epstein-Barr virus-induced G-protein coupled receptor 2 (EBI2) is a risk inflammatory bowel disease (IBD). Together with its oxysterol ligand 7α,25-dihydroxycholesterol, EBI2 mediates migration and differentiation of immune cells. However, the role in colonic system remains insufficiently studied. We found increased mRNA expression synthesizing enzymes (CH25H, CYP7B1) inflamed colon patients ulcerative colitis mice acute or chronic dextran sulfate sodium (DSS)...
Background: The diagnosis for several neurometabolic diseases is even nowadays often delayed or not at all possible. This among other things due to the variety of possible differential and very variable phenotypes. Furthermore, have clear biochemical measurement parameters. Therefore, already in 2017, supply project “TranslateNamse” was established 9 centers Germany collaboration with health insurances, following aim improving care patients rare diseases. „NeuroMetabolom“ a subproject within...
We report the first selective chemical probes for histone deacetylase 10 (HDAC10) with unprecedented selectivity over other HDAC isozymes. HDAC10 deacetylates polyamines and has a distinct substrate specificity, making it unique among 11 zinc-dependent hydrolases. Taking inspiration from polyamine substrates, we systematically inserted an amino group (“aza-scan”) into hexyl linker moiety of approved drug Vorinostat (SAHA). This one atom replacement (C-->N) transformed SAHA unselective...