- DNA Repair Mechanisms
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- PARP inhibition in cancer therapy
- Carcinogens and Genotoxicity Assessment
- Epigenetics and DNA Methylation
- Toxin Mechanisms and Immunotoxins
- Plant Toxicity and Pharmacological Properties
- Biochemical Acid Research Studies
- Colorectal Cancer Treatments and Studies
- Click Chemistry and Applications
- Genomics, phytochemicals, and oxidative stress
- Nutrition, Genetics, and Disease
- Computational Drug Discovery Methods
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Alcohol Consumption and Health Effects
- Glioma Diagnosis and Treatment
- Heme Oxygenase-1 and Carbon Monoxide
- Calcium signaling and nucleotide metabolism
- Drug Transport and Resistance Mechanisms
- Integrated Circuits and Semiconductor Failure Analysis
- Biotin and Related Studies
- ATP Synthase and ATPases Research
- Advanced Chemical Sensor Technologies
- Gut microbiota and health
University of Koblenz and Landau
2023-2024
Rheinland-Pfälzische Technische Universität Kaiserslautern-Landau
2023-2024
Justus-Liebig-Universität Gießen
2018-2024
University of Kaiserslautern
2019-2024
University Medical Center of the Johannes Gutenberg University Mainz
2013-2023
Johannes Gutenberg University Mainz
2013-2023
Daimler (Germany)
2023
University Medical Center
2019
University of Cagliari
2017
Universität Ulm
2009-2013
Poly(ADP-ribose) (PAR) is synthesized by poly(ADP-ribose) polymerases in response to genotoxic stress and interacts non-covalently with DNA damage checkpoint repair proteins. Here, we present a variety of techniques analyze this interaction terms selectivity affinity. In vitro PAR was end-labeled using carbonyl-reactive biotin analog. Binding HPLC-fractionated chains the tumor suppressor protein p53 nucleotide excision XPA assessed novel electrophoretic mobility shift assay (EMSA). Long...
Key biologic effects of the alpha-particle emitter Actinium-225 in comparison to beta-particle Lutetium-177 labeled somatostatin-analogue DOTATOC vitro and vivo were studied evaluate significance γH2AX-foci formation.To determine relative biological effectiveness (RBE) between two isotopes (as - consequence different ionisation-densities along a particle-track), somatostatin expressing AR42J cells incubated with Ac-225-DOTATOC Lu-177-DOTATOC up 48 h viability was analyzed using MTT assay....
Significance Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA repair protein and part of the genome maintenance network. On other hand, PARP-1 involved in pathophysiological processes such as inflammation. Chronic inflammation has emerged key event carcinogenesis, including formation colorectal cancer (CRC). Our data reveal that abundantly expressed human CRC, correlating with disease progression. Using transgenic mouse models, we show fosters inflammation-driven tumor growth stimulates...
DEK is a nuclear phosphoprotein implicated in oncogenesis and autoimmunity major component of metazoan chromatin. The intracellular cues that control the binding to DNA its pleiotropic functions DNA- RNA-dependent processes have remained mainly elusive so far. Our recent finding phosphorylation status altered during death receptor-mediated apoptosis suggested potential involvement stress signaling. In this study, we show cells committed die, portion cellular pool extensively...
DNA-damaging anticancer drugs remain a part of metastatic melanoma therapy. Epigenetic reprogramming caused by increased histone deacetylase (HDAC) activity arising during tumor formation may contribute to resistance melanomas the alkylating temozolomide, dacarbazine, and fotemustine. Here, we report on impact class I HDACs response malignant cells treated with agents. The data show that in situ contain high level HDAC1/2 overexpress HDAC1/2/3 compared noncancer cells. Furthermore,...
Abstract The consumption of red meat is probably carcinogenic to humans and associated with an increased risk develop colorectal cancer (CRC). Red contains high amounts heme iron, which thought play a causal role in tumor formation. In this study, we investigated the genotoxic cytotoxic effects iron (i.e., hemin) versus inorganic human colonic epithelial cells (HCEC), CRC cell lines murine intestinal organoids. Hemin catalyzed formation reactive oxygen species (ROS) induced oxidative DNA...
Abstract Liver cancer is one of the most frequent tumor entities worldwide, which causally linked to viral infection, fatty liver disease, life-style factors and food-borne carcinogens, particularly aflatoxins. Moreover, genotoxic plant toxins including phenylpropenes are suspected human carcinogens. The phenylpropene methyleugenol (ME) a constituent essential oils in many plants occurs herbal medicines, food, cosmetics. Following its uptake, ME undergoes Cytochrome P450 (CYP)...
Epidemiological studies indicate that N-nitroso compounds (NOC) are causally linked to colorectal cancer (CRC). NOC induce DNA alkylations, including O (6)-methylguanine (O (6)-MeG) and N-methylated purines, which repaired by (6)-MeG-DNA methyltransferase (MGMT) N-alkyladenine-DNA glycosylase (AAG)-initiated base excision repair, respectively. In view of recent evidence nonlinear mutagenicity for NOC-like compounds, the question arises as existence threshold doses in CRC formation. Here, we...
Abstract Activation of T cells, a major fraction peripheral blood lymphocytes (PBLCS), is essential for the immune response. Genotoxic stress resulting from ionizing radiation (IR) and chemical agents, including anticancer drugs, has serious impact on cells and, therefore, status. Here we compared sensitivity non-stimulated (non-proliferating) vs. CD3/CD28-stimulated (proliferating) PBLC to IR. PBLCs were highly sensitive IR surprisingly, stimulation proliferation resulted in resistance...
Alkylating agents are present in food and tobacco smoke, but also used cancer chemotherapy, inducing the DNA lesion O6-methylguanine. This critical adduct is repaired by O6-methylguanine-DNA methyltransferase (MGMT), resulting MGMT inactivation degradation. In study, we analyzed effects of natural disulfide compound lipoic acid (LA) on vitro colorectal cells. We show that LA, not its reduced form dihydrolipoic acid, potently inhibits activity recombinant interfering with catalytic Cys-145...
Background: Cardiac remodeling is modulated by overnutrition or starvation. The adipokine leptin mediates energy balance between adipose tissue and brain. Leptin its receptors are expressed in the heart. Methods Results: To examine importance of endothelial signaling cardiac hypertrophy, transverse aortic constriction was used mice with inducible endothelium-specific deletion (End.LepR-KO) littermate controls (End.LepR-WT). End.LepR-KO associated improved left ventricular function...
Poly(ADP-ribose) polymerase-1 (PARP-1) is a molecular DNA damage sensor that catalyzes the synthesis of complex biopolymer poly(ADP-ribose) (PAR) under consumption NAD(+). PAR engages in fundamental cellular processes such as metabolism and transcription interacts noncovalently with specific binding proteins involved repair regulation chromatin structure. A factor implicated organization DEK oncoprotein, an abundant conserved constituent metazoan chromatin, only member its protein class. We...
Werner syndrome is a premature aging disorder that caused by defects in the protein (WRN). WRN member of RecQ helicase family and possesses exonuclease activities. It involved various aspects DNA metabolism such as repair, telomere maintenance, replication. Poly(ADP-ribose) polymerase 1 (PARP1) also these processes catalyzing formation nucleic-acid-like biopolymer poly(ADP-ribose) (PAR). was previously shown interacts with PARP1 activity inhibited PARP1. Using several bioanalytical...
Abstract DNA double-strand breaks (DSBs) are critical lesions, which threaten genome stability and cell survival. DSBs directly induced by ionizing radiation (IR) radiomimetic agents, including the cytolethal distending toxin (CDT). This bacterial genotoxin harbors a unique DNase-I-like endonuclease activity. Here we studied role of CDT IR as trigger autophagy, is cellular degradation process involved in homeostasis, protection cancer. The regulatory mechanisms DSB-induced autophagy were...