A5021947195- Chemotherapy-induced cardiotoxicity and mitigation
- Pluripotent Stem Cells Research
- Cardiac Ischemia and Reperfusion
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Radiation Effects in Electronics
- Genetics, Aging, and Longevity in Model Organisms
- Tissue Engineering and Regenerative Medicine
- Spaceflight effects on biology
- Chromium effects and bioremediation
- Neuroscience and Neural Engineering
- Immune cells in cancer
- Cardiac Fibrosis and Remodeling
- Takotsubo Cardiomyopathy and Associated Phenomena
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Eicosanoids and Hypertension Pharmacology
- Enzyme-mediated dye degradation
- Computational Drug Discovery Methods
- Research on Leishmaniasis Studies
- Insect Resistance and Genetics
- Phagocytosis and Immune Regulation
- Integrated Circuits and Semiconductor Failure Analysis
- Toxin Mechanisms and Immunotoxins
- Radiation Therapy and Dosimetry
- Cancer-related cognitive impairment studies
University Hospital Cologne
2022-2024
University of Cologne
2014-2024
Lupin Pharmaceuticals (India)
2021
National Centre for Cell Science
2010-2012
The currently available techniques for the safety evaluation of candidate drugs are usually cost-intensive and time-consuming often insufficient to predict human relevant cardiotoxicity. purpose this study was develop an in vitro repeated exposure toxicity methodology allowing identification predictive genomics biomarkers functional relevance drug-induced cardiotoxicity induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). hiPSC-CMs were incubated with 156 nM doxorubicin, which...
An in depth investigation at the genomic level is needed to identify early human-relevant cardiotoxicity biomarkers that are induced by drugs and environmental toxicants. The main objective of this study was investigate role microRNAs (miRNAs) as using human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) were exposed doxorubicin (DOX) a “gold standard” cardiotoxicant. hiPSC-CMs 156 nM DOX for 2 days or 6 repeated exposure, followed drug washout incubation drug-free...
Etoposide (ETP) and anthracyclines are applied for wide anti-cancer treatments. However, the ETP-induced cardiotoxicity remains to be a major safety issue underlying cardiotoxic mechanisms not well understood. This study is aiming unravel profile of ETP in comparison using physiologically relevant human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). Using xCELLigence real-time cell analyser (RTCA), we found that single high dose induces irreversible increase hPSC-CMs beating rate...
Embryonic developmental studies under microgravity conditions in space are very limited. To study the effects of altered gravity on embryonic development processes we established an vitro methodology allowing differentiation mouse stem cells (mESCs) simulated within a fast-rotating clinostat (clinorotation) and capture microarray-based gene signatures.The differentiating mESCs were cultured 2D pipette clinostat. The microarray bioinformatics tools used to genes that deregulated by their...
Exposure to outer space microgravity poses a risk for the development of various pathologies including cardiovascular disease. To study this, we derived cardiomyocytes (CMs) from human-induced pluripotent stem cells and exposed them simulated (SMG). We combined different "omics" chromosome conformation capture technologies with live-cell imaging transgenic lines discover that SMG impacts on contractile velocity function CMs via induction senescence processes. This is linked SMG-induced...
Background: Abdominal aortic aneurysms (AAA) are characterized by an intricate interplay of extracellular matrix degradation and inflammation. Macrophages centrally involved in these processes. The mechanisms underlying macrophage activation AAA remain incompletely understood. Vascular macrophages have been shown to express olfactory receptor 2 (Olfr2), a G-protein coupled mediating the sense smelling regulating inflammatory activity macrophages. Whether Olfr2 plays role modulating responses...
Necroptosis is an inflammatory form of regulated cell death implicated in a range human pathologies, whose execution depends on the poorly understood pseudokinase mixed lineage kinase domain-like (MLKL). Here, we report that splicing-dependent insertion short amino acid sequence C-terminal α-helix (Hc) MLKL abolishes killing activity and creates anti-necroptotic isoform counteracts induced by necroptosis-proficient protein mice humans. We show interaction Hc with previously unrecognized...
Visceral leishmaniasis or kala azar is the most severe form of and caused by protozoan parasite Leishmania donovani . There no published report on L. genome sequence available till date, although sequences three related species are already available. Thus, we took a proteogenomic approach to identify proteins from two different life stages From our analysis promastigote (insect) amastigote (human) , identified total 22322 unique peptides homology‐based search against species. These were...
Cardiotoxicity is a major complication of anthracycline therapy that negatively impacts prognosis. Effective pharmacotherapies for prevention anthracycline-induced cardiomyopathy (AICM) are currently lacking. Increased plasma levels the neutrophil-derived enzyme myeloperoxidase (MPO) predict occurrence AICM in humans. We hypothesized MPO release causally contributes to AICM. Mice intravenously injected with doxorubicin (DOX) exhibited higher neutrophil counts and circulation cardiac tissue...
There is a large demand of human relevant in vitro test system suitable for assessing the cardiotoxic potential cosmetic ingredients and other chemicals. Using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), we have already established an cardiotoxicity assay identified genomic biomarkers anthracycline-induced our previous work. Here, five were studied by new hiPSC-CMs test; kojic acid (KJA), triclosan (TS), triclocarban (TCC), 2,7-naphthalenediol (NPT), basic red 51...
Introduction Myocardial infarction (MI) is a significant contributor to morbidity and mortality worldwide. Many individuals who survive the acute event continue experience heart failure (HF), with inflammatory healing processes post-MI playing pivotal role. Polymorphonuclear neutrophils (PMN) monocytes infiltrate infarcted area, where PMN release high amounts of heme enzyme myeloperoxidase (MPO). MPO has numerous properties plasma levels are correlated prognosis severity MI. While studies...
Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. Improved survival has led to an increasing incidence ischemic cardiomyopathy, making it major reason for hospitalization in the western world. The inflammatory response myocardium determines extent structural remodeling functional deterioration, with neutrophils (PMN) being key modulator propagation resolution inflammation. heme enzyme myeloperoxidase (MPO) abundantly expressed PMN important mediator their...
Live-cell imaging techniques are essential for acquiring vital physiological and pathophysiological knowledge to understand treat heart disease. For live-cell of transient alterations [Ca2+]i in human cardiomyocytes, we engineered human-induced pluripotent stem cells carrying a genetically-encoded Ca2+-indicator (GECI). To monitor sarcomere shortening relaxation cardiomyocytes real-time, generated α-cardiac actinin (ACTN2)-copepod (cop) green fluorescent protein (GFP+)-human-induced cell...
Myeloperoxidase (MPO) is an enzyme that functions in host defense. MPO released into the vascular lumen by neutrophils during inflammation and may adhere subsequently penetrate endothelial cells (ECs) coating walls. We show enters nucleus of ECs binds chromatin independently its enzymatic activity. drives decondensation at binding sites enhances condensation neighboring regions. It loci relevant for endothelial-to-mesenchymal transition (EndMT) affects migratory potential ECs. Finally,...
Application of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is limited by the challenges in their efficient differentiation. Recently, Wingless (Wnt) signaling pathway has emerged as key regulator cardiomyogenesis. In this study, we evaluated effects cyclooxygenase inhibitors on cardiac differentiation hPSCs. Cardiac was performed adherent monolayer based method using 4 hPSC lines (HES3, H9, IMR90, and ES4SKIN). The efficiency flow cytometry RT-qPCR. Generated hPSC-CMs were...
The role of calcium release-activated (CRAC) channels is well characterized and particular importance in T-cell function. CRAC are involved the pathogenesis several autoimmune diseases, making it an attractive therapeutic target for treating inflammatory like rheumatoid arthritis (RA). A systematic structure-activity relationship study with goal optimizing lipophilicity successfully yielded two lead compounds, 36 37. Both compounds showed decent potency selectivity a remarkable...
Abstract Background Abdominal aortic aneurysms (AAA) are defined as enlargement above 3cm or 50% of its original diameter. Therapeutic options limited to surgical and endovascular treatment, while no pharmacological interventions available. Chronic inflammation the vessel wall in particularly macrophage infiltration has been associated with disease progression, leading extensive tissue remodeling, yet underlying mechanisms incompletely understood. A recent study shown extra-nasal expression...
Significant evidence points to Strip2 being a key regulator of the differentiation processes pluripotent embryonic stem cells. However, mediated epigenetic regulation and development is quite unknown. Here, we identified several interaction partners Strip2, importantly co-repressor molecular protein complex nucleosome remodeling deacetylase/Tripartite motif-containing 28/Histone deacetylases/Histone-lysine N-methyltransferase SETDB1 (NuRD/TRIM28/HDACs/SETDB1) histone methyltransferase, which...
Exposure to outer space microgravity poses a risk for the development of various pathologies including cardiovascular disease. To study this, we derived cardiomyocytes (CMs) from human induced pluripotent stem cells and exposed them simulated (SMG). We combined different “omics” chromosome conformation capture technologies with live-cell imaging transgenic lines discover that SMG impacts on contractile velocity function CMs via induction senescence processes. This is linked SMG-induced...