A5052041258- Environmental Science and Technology
- Lipoproteins and Cardiovascular Health
- Inflammasome and immune disorders
- T-cell and B-cell Immunology
- RNA regulation and disease
- Liver Disease Diagnosis and Treatment
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Immunotherapy and Immune Responses
- Advanced biosensing and bioanalysis techniques
- Immune Cell Function and Interaction
- Endoplasmic Reticulum Stress and Disease
- Ubiquitin and proteasome pathways
- DNA and Nucleic Acid Chemistry
- Systemic Lupus Erythematosus Research
- Autophagy in Disease and Therapy
- Immune Response and Inflammation
- Hepatitis C virus research
- Dialysis and Renal Disease Management
- Bacterial Genetics and Biotechnology
- Drug Transport and Resistance Mechanisms
- Global trade, sustainability, and social impact
- Nitric Oxide and Endothelin Effects
- Immune cells in cancer
- PI3K/AKT/mTOR signaling in cancer
- Liver physiology and pathology
University of Bonn
2019-2024
Technical University of Munich
2014-2019
German Cancer Research Center
2019
Heidelberg University
2019
Klinikum rechts der Isar
2016-2018
Whitehead Institute for Biomedical Research
2012-2016
Innsbruck Medical University
1998-2013
Massachusetts Institute of Technology
2012
Ministry of Defense
2009
Microbial Chemistry Research Foundation
2009
Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the spectrum 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration phosphoproteomic...
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread, with devastating consequences. For passive immunization efforts, nanobodies have size and cost advantages over conventional antibodies. In this study, we generated four neutralizing that target the receptor binding domain of SARS-CoV-2 spike protein. We used x-ray crystallography cryo-electron microscopy define two distinct epitopes. On basis these structures, engineered multivalent more...
Clearance of invading microbes requires phagocytes the innate immune system. However, successful pathogens have evolved sophisticated strategies to evade killing. The opportunistic human fungal pathogen Candida albicans is efficiently phagocytosed by macrophages, but causes inflammasome activation, host cytolysis, and escapes after hypha formation. Previous studies suggest that macrophage lysis C. results from early inflammasome-dependent cell death (pyroptosis), late damage due glucose...
Abstract Fungal β-glucan, such as curdlan, triggers antifungal innate immune responses well shaping adaptive responses. In this study, we identified a key pathway that couples curdlan to Curdlan promoted the production of proinflammatory cytokine IL-1β by dendritic cells and macrophages through NLRP3 inflammasome. Stimulation with Candida albicans Saccharomyces cerevisiae also triggered inflammasome-mediated production. vivo, was required for efficient Ag-specific Ab when used an adjuvant,...
Aberrant tumor-intrinsic RIG-I signaling is a crucial mechanism underlying cancer resistance to anti–CTLA-4 immunotherapy.
Highlights•Vav proteins control CLR-mediated inflammatory responses•CLR-induced NF-κB activation is regulated by Vav proteins•Vav/Card9 signaling critical for antifungal host defenseSummaryFungal infections are major causes of morbidity and mortality, especially in immunocompromised individuals. The innate immune system senses fungal pathogens through Syk-coupled C-type lectin receptors (CLRs), which signal the conserved adaptor Card9. Although Card9 essential defense, mechanisms that couple...
Tripartite ATP-independent periplasmic (TRAP) transporters are found widely in bacteria and archaea consist of three structural domains, a soluble substrate-binding protein (P-domain), two transmembrane domains (Q- M-domains). HiSiaPQM its homologs TRAP for sialic acid essential host colonization by pathogenic bacteria. Here, we reconstitute HiSiaQM into lipid nanodiscs use cryo-EM to reveal the structure transporter. It is composed 16 helices that unexpectedly structurally related...
Premature cardiovascular disease is the leading cause of death in patients with end-stage renal treated by hemodialysis (HD). Low-density lipoprotein (LDL) levels are not generally increased HD patients, but their LDL metabolism still poorly understood. We therefore investigated vivo apoB-containing lipoproteins two different ethnic populations and controls.We performed stable isotope kinetic studies using a primed constant infusion deuterated leucine 12 13 healthy controls. Tracer/tracee...
Hemodialysis patients often present with increased concentrations of tryptophan catabolites perhaps related to an enhanced activity tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) that is inducible by pro-inflammatory stimuli. The chronic inflammation and immune activation status in dialysis may accelerate degradation, which could influence patients' psychological performance.In this study, plasma kynurenine were determined HPLC 75 patients, aged 65.3 ± 15.0 years. Forty...
To study the CD8 + T cell response against a mouse gherpes virus, we generated K b -MHV-68-ORF8 604-612 RAG À/À receptor transnuclear (TN) mice as source of virus-specific cells.K -ORF8-Tet cells, expanded in course resolving MHV-68 infection, served nucleus donors.Various vivo and ex assay criteria demonstrated fine specificity functionality TN cells.TN cells proliferated extensively to viral helped control burden, exhibited phenotype similar that endogenous cells.When compared OT-1...
Abstract When pyrene butyric acid hydrazide or acetic is attached to single‐strand RNA 3′ termini a red shift in absorbance and substantial hypochromicity are observed. A strong induced CD seen the fluorescence intensity quenched by an order of magnitude. In double‐stranded samples, further 10‐fold quenching seen. Several lines evidence suggest that residual hydrazide‐duplex conjugates arises from minor species. The most likely possibility dye reacted at site other than end. Some indication...
Multiple sclerosis (MS) is an autoimmune disease that affects the CNS. One approved treatment for relapsing forms of MS YEAK, a random copolymer amino acids tyrosine, glutamic acid, alanine, and lysine. YFAK, second-generation composed phenylalanine, lysine, more successful in treating experimental encephalomyelitis, mouse model MS. Although originally designed optimized based on autoantigen myelin basic protein (MBP) MBP-derived peptide MBP85-99 presented to MS-associated class II MHC...
Abstract The tripartite ATP-independent periplasmic (TRAP) transporters enable Vibrio cholerae and Haemophilus influenzae to acquire sialic acid, aiding their colonization of human hosts. This process depends on SiaP, a substrate-binding protein (SBP) that captures delivers acid the transporter. We identified 11 nanobodies bind specifically SiaP proteins from H. (HiSiaP) V. (VcSiaP). Two inhibited binding. Detailed structural biophysical studies one nanobody-SBP complex revealed an...
Summary Background and objectives In vivo metabolism of atherogenic apolipoprotein B (apoB)–containing lipoproteins is severely impaired in patients undergoing hemodialysis (HD), resulting markedly prolonged residence times these particles. It unclear whether treatment with statins improves LDL kinetics HD as known for the general population. Therefore, this kinetic study assessed apoB-containing patients. Design, setting, participants, & measurements Kinetic measures were analyzed...