A5049425789- Immune Cell Function and Interaction
- Extracellular vesicles in disease
- PARP inhibition in cancer therapy
- Immune cells in cancer
- Cell death mechanisms and regulation
- MicroRNA in disease regulation
- Mast cells and histamine
- Reproductive System and Pregnancy
- Immune Response and Inflammation
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Chronic Myeloid Leukemia Treatments
- Advanced biosensing and bioanalysis techniques
- Histone Deacetylase Inhibitors Research
- NF-κB Signaling Pathways
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer-related gene regulation
- Cardiovascular Disease and Adiposity
- Microgrid Control and Optimization
- Pesticide Exposure and Toxicity
- Carcinogens and Genotoxicity Assessment
- Effects of Radiation Exposure
- IL-33, ST2, and ILC Pathways
- RNA Interference and Gene Delivery
- Toxin Mechanisms and Immunotoxins
Philipps University of Marburg
2020-2024
Johannes Gutenberg University Mainz
2017-2021
University Medical Center of the Johannes Gutenberg University Mainz
2017-2021
University of Konstanz
2010-2015
Despite the frequent use of ionising radiation (IR) in therapy and diagnostics unavoidable exposure to external sources, our knowledge regarding radiosensitivity human blood cell populations is limited published data, obtained under different experimental conditions, are heterogeneous. To compare hematopoietic populations, we set out determine responses cells from peripheral healthy volunteers identical conditions (resting, non-stimulated cells). First, measured response T (Treg, Th, CTL), B...
Recent studies reveal a critical role of tumor cell-released extracellular vesicles (EVs) in pancreatic cancer (PC) progression. However, driver genes that direct EV function, the EV-recipient cells, and their cellular response to uptake remain be identified. Therefore, we studied Bcl-2-associated-anthanogene 6 (BAG6), regulator biogenesis for We used Cre recombinase/LoxP-based reporter system combination with single-cell RNA sequencing monitor vivo microenvironment (TME) changes mouse...
Monocytes and their descendants, macrophages, play a key role in the defence against pathogens. They also contribute to pathogenesis of inflammatory diseases. Therefore, mechanism maintaining balance monocyte/macrophage population must be postulated. Our previous studies have shown that monocytes are impaired DNA repair, rendering them vulnerable genotoxic stress while monocyte-derived macrophages repair competent stress-resistant. Based on these findings, we hypothesized can selectively...
Arachidonic acid (AA) is a polyunsaturated fatty present at high concentrations in the ovarian cancer (OC) microenvironment and associated with poor clinical outcome. In study, we have unraveled potential link between AA macrophage functions. Methods: AA-triggered signal transduction was studied primary monocyte-derived macrophages (MDMs) by phosphoproteomics, transcriptional profiling, measurement of intracellular Ca2+ accumulation reactive oxygen species production conjunction...
The immunoreceptor NKG2D, which is expressed on NK cells and T cell subsets critically involved in tumor immune surveillance. This applies particular to acute myeloid leukemia (AML), evades detection by downregulation of NKG2D ligands (NKG2D-L), including MICA. absence NKG2D-L AML moreover associated with stem characteristics. NKG2D/NKG2D-L system thus qualifies as an interesting promising therapeutic target.Here we aimed identify transcription factors susceptible pharmacological stimulation...
Abstract Background TP53 , encoding the tumor suppressor p53, is frequently mutated in various cancers, producing mutant p53 proteins (mutp53) which can exhibit neomorphic, gain-of-function properties. The latter transform into an oncoprotein that promotes metastatic progression via downstream effectors such as ENTPD5, endoplasmic reticulum UDPase involved calnexin/calreticulin cycle of N-glycoprotein biosynthesis. Elucidating mechanisms underlying pro-metastatic functions mutp53-ENTPD5 axis...
NKp30 (Natural Cytotoxicity Receptor 1, NCR1) is a powerful cytotoxicity receptor expressed on natural killer (NK) cells which involved in tumor cell killing and the regulation of antitumor immune responses. Ligands for NKp30, including BAG6 B7-H6, are upregulated virus-infected but rarely detectable healthy cells. These ligands released by as part cellular secretome interfere with NK activity. secreted via exosomal pathway, BAG6-positive extracellular vesicles (EV-BAG6) trigger cytokine...
The DNA repair protein O 6-methylguanine-DNA-methyltransferase (MGMT) is a key determinant of cancer resistance. MGMT inhibitors 6-benzylguanine (O6BG) and 6-(4-bromothenyl)guanine (O6BTG) failed to enhance the therapeutic response due toxic side effects when applied in combination with alkylating chemotherapeutics, indicating need inhibitor targeting. We assessed targeting that relies on conjugating O6BG O6BTG ß-D-glucose, resulting O6BG-Glu O6BTG-Glu, respectively. This strategy was...
Experimental data demonstrated that the regenerative potential and immunomodulatory capacity of Cardiosphere-Derived Cells (CDCs) is mediated by paracrine mechanisms. In this process, extracellular vesicles derived from CDCs (EV-CDCs) are key mediators their therapeutic effect. Considering future applicability these in human diseases, an accurate preclinical-to-clinical translation needed, as well exhaustive molecular characterization animal-derived products. Based on that, main goal study...
In previous studies, we showed impaired DNA repair in human monocytes. Here, addressed the question of whether neutrophilic granulocytes that arise from same precursor as monocytes exhibit a similar phenotype and are repairing their DNA. We show isolated peripheral blood display lack proteins missing do not when damaged by ionising radiation (IR) or chemical ROS. Contrary to T cells, observed no decline number single-strand breaks following γ-radiation. Also, did γH2AX foci formation while...
Drugs targeting epigenetic mechanisms such as histone deacetylase inhibitors (HDACi) suppress tumor growth. HDACi also induce the expression of ligands for cytotoxicity receptor NKG2D rendering tumors more susceptible to natural killer (NK) cell-dependent killing. The major acetylases responsible (NKG2D-L) are CBP and p300. role oncogene transcriptional repressor SKI, an essential part HDAC-recruiting co-repressor complex, which competes with CBP/p300 binding SMAD3 in TGFβ signaling, is...
The unbiased identification of less-abundant transcription factors, which direct the expression a target gene, is technically challenging. Here, we present protocol to analyze locus-specific chromatin-regulating proteome using in situ capture chromatin interactions by an inactive Cas9 (dCas9). We describe steps for designing guide RNAs and transfection, followed precipitation associated proteins. In last step, elution DNA proteins PCR mass spectrometric analysis, respectively. For complete...
One of the most important targets for natural killer (NK) cell-mediated therapy is induction group 2D ligand (NKG2D-L) expression. APTO253 a small molecule that selectively kills acute myeloid leukemia (AML) cells, and it has been reported can induce Krüppel-like factor 4 (KLF4) expression downregulate c-MYC Recently, we discovered novel role in modulating NK cell response by inducing surface NKG2D-Ls, especially MHC class I polypeptide-related sequence A (MICA), AML cells. In this study,...