A5014263080- DNA and Nucleic Acid Chemistry
- Liver physiology and pathology
- Click Chemistry and Applications
- Metal complexes synthesis and properties
- Nanomaterials for catalytic reactions
- Cancer, Hypoxia, and Metabolism
- Cancer Cells and Metastasis
- DNA Repair Mechanisms
- Pancreatic and Hepatic Oncology Research
- Cancer therapeutics and mechanisms
- Pharmacogenetics and Drug Metabolism
- Neuroscience of respiration and sleep
- Microtubule and mitosis dynamics
- Immune Response and Inflammation
- Neuroscience and Neural Engineering
- Nitric Oxide and Endothelin Effects
- Neuroscience and Neuropharmacology Research
- Cancer-related Molecular Pathways
- Pain Mechanisms and Treatments
- Neuroendocrine regulation and behavior
- Heat shock proteins research
- Neural dynamics and brain function
- Caveolin-1 and cellular processes
- FOXO transcription factor regulation
- TGF-β signaling in diseases
Merck (Germany)
2013-2023
Merck Serono (Italy)
2015
Boehringer Ingelheim (Germany)
2006
Natural and Medical Sciences Institute
2004
University of Tübingen
2004
Justus-Liebig-Universität Gießen
2001-2003
University of Hohenheim
2000-2002
Max Planck Institute for Heart and Lung Research
1994-1998
Max Planck Society
1997
Physical and chemical DNA-damaging agents are used widely in the treatment of cancer. Double-strand break (DSB) lesions DNA most deleterious form damage and, if left unrepaired, can effectively kill cancer cells. DNA-dependent protein kinase (DNA-PK) is a critical component nonhomologous end joining (NHEJ), one two major pathways for DSB repair. Although DNA-PK has been considered an attractive target therapy, development pharmacologic inhibitors clinical use lagging. Here, we report...
Abstract Purpose: The mesenchymal–epithelial transition factor (c-Met) receptor, also known as hepatocyte growth receptor (HGFR), controls morphogenesis, a process that is physiologically required for embryonic development and tissue repair. Aberrant c-Met activation associated with variety of human malignancies including cancers the lung, kidney, stomach, liver, brain. In this study, we investigated properties two novel compounds developed to selectively inhibit in antitumor therapeutic...
Radiotherapy and chemical DNA-damaging agents are among the most widely used classes of cancer therapeutics today. Double-strand breaks (DSB) induced by many these treatments lethal to cells if left unrepaired. Ataxia telangiectasia-mutated (ATM) kinase plays a key role in DNA damage response driving DSB repair cell-cycle checkpoints protect cells. Inhibitors ATM catalytic activity have been shown suppress repair, block checkpoint controls enhance therapeutic effect radiotherapy other...
Mammalian Staufen2 (Stau2) is a member of the double-stranded RNA-binding protein family. Its expression largely restricted to brain. It thought play role in delivery RNA dendrites polarized neurons. To investigate function Stau2 mature neurons, we interfered with by interference (RNAi). Mature neurons lacking displayed significant reduction number dendritic spines and an increase filopodia-like structures. The PSD95-positive synapses miniature excitatory postsynaptic currents were markedly...
Interleukin-6 (IL-6) is regarded as an endogenous mediator of lipopolysaccharide (LPS)-induced fever. IL-6 thought to act on the brain at sites that lack a blood-brain barrier, circumventricular organs (CVOs). Cells are activated by respond with nuclear translocation signal transducer and activator transcription 3 molecule (STAT3) can be detected immunohistochemistry. We investigated whether LPS-induced release into systemic circulation was accompanied STAT3 within sensory CVOs. Treatment...
Abstract Certain members of the olfactory receptor superfamily appear to be expressed not only in chemosensory neurons nasal epithelium. Analyzing transgenic mouse line MOL2.3‐IGITL , subtype MOL2.3 was found distinct subpopulations cells within a cranial, cervical as well thoracic ganglion. By means coexpressed markers, axonal processes expressing could visualized and thus target tissues innervated by these ganglionic identified. Stained fibers, but no stained cell bodies were visible head...
Mass spectrometry (MS) is known for its label-free detection of substrates and products from a variety enzyme reactions. Recent hardware improvements have increased interest in the use matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS high-throughput drug discovery. Despite this technology, several challenges remain must be overcome before MALDI-MS can integrated as an automated "in-line reader" Two such hurdles include situ sample processing deposition, well...
Abstract Physical or chemical agents that damage DNA such as ionizing radiation are among the most widely used classes of cancer therapeutics today. Double strand breaks (DSB) generated in by induce multitude cellular responses, including repair, cell cycle arrest death if is left unrepaired. A complex set molecular events responsible for repair via two major mechanisms - homologous recombination (HR) non-homologous end joining (NHEJ). DNA-PKcs with its regulatory protein subunits, Ku70 and...
In guinea pigs, dose-dependent febrile responses can be induced by injection of a high (100 μg/kg) or low (10 dose bacterial lipopolysaccharide (LPS) into artificial subcutaneously implanted Teflon chambers. this fever model, LPS does not enter the systemic circulation from site localized tissue inflammation in considerable amounts but causes local induction proinflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6), which measured lavage fluid collected chamber area....
As numerous diseases have been shown to be related dysfunction of ion channels and neurotransmitter receptors affect regulatory pathways, attracted increasing attention as a target class for drug discovery. The concomitant demand the pharmaceutical industry adequate electrophysiological methods investigate effects on specific in secondary safety screening has resulted development instrumentation that allows automated monitoring channel function with higher throughput. Here we tested fully...
1. The inherent temperature sensitivity of 343 spontaneously active neurones recorded from rat spinal cord (SC) slices was investigated electrophysiologically. Recordings were made 321 neurons transverse and 22 longitudinal their thermosensitivity determined by relating changes in firing rate to slice temperature. 2. Of the slices, 53% warm sensitive, 2% cold sensitive 45% insensitive. In 68% remaining 3. When classified according recording sites warm‐sensitive laminae I II had same mean...
Vesicular V-ATPase (V-type H+-ATPase) and the plasma membrane-bound Na+/K+-ATPase are essential for cycling of neurotransmitters at synapse, but direct functional studies on their action in native surroundings limited due to poor accessibility via standard electrophysiological equipment. We performed SSM (solid supported membrane)-based analyses synaptic vesicles membranes prepared from rat brains by sucrose-gradient fractionation. Acidification experiments revealed activity fractions...
NIMA-related kinase 1 (Nek1) has lately garnered attention for its widespread function in ciliogenesis, apoptosis, and the DNA-damage response. Despite involvement various diseases potential as a cancer drug target, no directed medicinal chemistry efforts toward inhibitors against this dark are published. Here, we report structure-guided design of potent small-molecule Nek1 inhibitor, starting from scaffold identified by cross-screening analysis. Seven lead compounds were silico evaluated...
Abstract The protein kinase ataxia telangiectasia- mutated and Rad3-related (ATR) is an important component of the DNA Damage Response (DDR) a key mediator replication stress response (RSR). ATR recruited to activated by single-stranded DNA, which commonly forms as consequence (RS). activation signaling coordinates multifaceted RS, however if left unresolved, forks may collapse, form double-strand breaks (DSB), lead chromosomal rearrangements eventually cell death. Several chemotherapeutic...