A5087046470- Parasites and Host Interactions
- Parasite Biology and Host Interactions
- Invertebrate Immune Response Mechanisms
- Advanced Glycation End Products research
- Trypanosoma species research and implications
- Mosquito-borne diseases and control
- Insect symbiosis and bacterial influences
- Epigenetics and DNA Methylation
- Macrophage Migration Inhibitory Factor
- HIV Research and Treatment
- Trace Elements in Health
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- RNA modifications and cancer
- Insect Resistance and Genetics
- HVDC Systems and Fault Protection
- Synthesis and Biological Evaluation
- Antimicrobial Peptides and Activities
- Helminth infection and control
- Heme Oxygenase-1 and Carbon Monoxide
- NF-κB Signaling Pathways
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Coenzyme Q10 studies and effects
- Calcium signaling and nucleotide metabolism
- Alzheimer's disease research and treatments
German Cancer Research Center
2018-2025
Heidelberg University
2018-2025
Universidade Federal do Rio de Janeiro
2009-2024
DKFZ-ZMBH Alliance
2018-2023
Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular
2016-2018
Instituto de Biotecnología y Biología Molecular
2012
Oxidative damage contributes to microbe elimination during macrophage respiratory burst. Nuclear factor, erythroid-derived 2, like 2 (NRF2) orchestrates antioxidant defenses, including the expression of heme-oxygenase-1 (HO-1). Unexpectedly, activation NRF2 and HO-1 reduces infection by a number pathogens, although mechanism responsible for this effect is largely unknown. We studied Trypanosoma cruzi in mice which NRF2/HO-1 was induced with cobalt protoporphyrin (CoPP). CoPP reduced...
Chronic chagasic cardiomyopathy (CCC) develops years after acute infection by Trypanosoma cruzi and does not improve trypanocidal therapy, despite reduction of parasite burden. During disease, the heart undergoes oxidative stress, a potential causative factor for arrhythmias contractile dysfunction. Here we tested whether antioxidants/ cardioprotective drugs could cardiac function in established Chagas disease. We chose model that resembles B1-B2 stage human CCC, treated mice with...
The parthenogenetic marbled crayfish (Procambarus virginalis) is a novel species that has rapidly invaded and colonized various different habitats. Adaptation to environments appears be independent of the selection genetic variants, but epigenetic programming genome remains understood. Here, we provide comprehensive analysis DNA methylation in crayfish. Whole-genome bisulfite sequencing multiple replicates tissues revealed pattern characterized by gene body housekeeping genes. Interestingly,...
Treatment and control of schistosomiasis relies on the only available drug, praziquantel, search for alternative chemotherapeutic agents is therefore urgent. Egg production required transmission immunopathology females S. mansoni lay 300 eggs daily. A large fraction total mRNA in mature female worm encodes one eggshell protein, Smp14. We report that nuclear receptors SmRXR1 SmNR1 regulate Smp14 transcription through recruitment two histone acetyltransferases (HATs), SmGCN5 SmCBP1. The...
The marbled crayfish (Procambarus virginalis) is a monoclonal, parthenogenetically reproducing freshwater species that has formed multiple stable populations worldwide. Madagascar hosts particularly large and rapidly expanding colony of in unique environment characterized by very high degree ecological diversity. Here we provide detailed characterization five their habitats. Our data show the animals can tolerate wide range parameters, consistent with invasive potential. While detected...
Abstract N6-Methyladenosine (m6A) is the most prevalent internal modification of eukaryotic mRNAs and affects regulation its target transcripts in all aspects mRNA life cycle. Cancer-associated changes m6A epitranscriptomic landscape as well deregulation regulators have been linked to cancer development. However, studies focused on vitro or vivo models antibody-dependent mapping techniques, which limited resolution lack quantitative methylation information. Here, we provide first...
In chronic schistosomiasis, liver fibrosis is linked to portal hypertension, which a condition associated with high mortality and morbidity. High mobility group box 1 (HMGB1) was originally described as nuclear protein that functions structural co-factor in transcriptional regulation. However, HMGB1 can also be secreted into the extracellular milieu under appropriate signal stimulation. Extracellular acts multifunctional cytokine contributes infection, injury, inflammation, immune responses...
Background The possibility of emergence praziquantel-resistant Schistosoma parasites and the lack other effective drugs demand discovery new schistosomicidal agents. In this context study compounds that target histone-modifying enzymes is extremely promising. Our aim was to investigate effect inhibition EZH2, a histone methyltransferase involved in chromatin remodeling processes gene expression control; we tested different developmental forms mansoni using GKS343, selective inhibitor EZH2...
Aedes aegypti mosquitoes are important vectors of viral diseases. Mosquito host factors play key roles in virus control and it has been suggested that dengue replication is regulated by Dnmt2-mediated DNA methylation. However, recent studies have shown Dnmt2 a tRNA methyltransferase Dnmt2-dependent methylomes lack defined methylation patterns, thus necessitating systematic re-evaluation the mosquito genome status. We now searched Ae. for candidate modification enzymes. This failed to reveal...
Schistosoma mansoni HMGB1 (SmHMGB1) was revealed to be a substrate for the parasite histone acetyltransferases SmGCN5 and SmCBP1. We found that full-length SmHMGB1, as well its HMG-box B (but not A) were acetylated in vitro by However, SmCBP1 able acetylate both substrates more efficiently than SmGCN5. Interestingly, removal of C-terminal acidic tail SmHMGB1 (SmHMGB1ΔC) resulted increased acetylation protein. showed mammalian cell transfection assays SmHMGB1ΔC transported from nucleus...
Treatment and control of schistosomiasis still rely on only one effective drug, praziquantel (PZQ) and, due to mass treatment, the increasing risk selecting for schistosome strains that are resistant PZQ has alerted investigators urgent need develop novel therapeutic strategies. The histone-modifying enzymes (HMEs) represent promising targets development epigenetic drugs against Schistosoma mansoni. In present study, we targeted S. mansoni lysine-specific demethylase 1 (SmLSD1), a...
DNA methylation is an important epigenetic modification that has been repeatedly implied in organismal adaptation. However, many previous studies have linked patterns to environmental parameters limited by confounding factors, such as cell-type heterogeneity and genetic variation. In this study, we analyzed variation marbled crayfish, a clonal invasive freshwater crayfish characterized largely tissue-invariant methylome negligible Using capture-based subgenome bisulfite sequencing approach...
Background The helminth Schistosoma mansoni parasite resides in mesenteric veins where fecundated female worms lay hundred of eggs daily. Some the egg antigens are trapped liver and induce a vigorous granulomatous response. High Mobility Group Box 1 (HMGB1), nuclear factor, can also be secreted act as cytokine. Schistosome HMGB1 (SmHMGB1) is by stimulate production key cytokines involved pathology schistosomiasis. Thus, understanding mechanism SmHMGB1 release becomes mandatory. Here, we...
The mosquito Aedes aegypti can spread the dengue, chikungunya and yellow fever viruses. Thus, search for key molecules involved in survival represents today a promising vector control strategy. High Mobility Group Box (HMGB) proteins are essential nuclear factors that maintain high-order structure of chromatin, keeping eukaryotic cells viable. Outside nucleus, secreted HMGB could alert innate immune system to foreign antigens trigger initiation host defenses. In this work, we cloned...
Background 3-(3-chloro-phenyl)-5-(4-pyridyl)-4,5-dihydroisoxazole (DIC) is a five-membered heterocyclic compound containing N-O bond. The anti-inflammatory effects of this were studied both in vitro and vivo. Principal Findings DIC effectively decreased TNF-α IL-6 release from LPS-stimulated macrophages dose dependent manner. diminished the levels COX-2 with subsequent inhibition PGE2 production. also compromised HMGB1 translocation nucleus to cytoplasm. Moreover, prevented nuclear NF-κB...
METTL3 is the major writer of N6-Methyladenosine (m6A) and has been associated with controversial roles in cancer. This best illustrated urothelial carcinoma bladder (UCB), where was described to have both oncogenic tumor-suppressive functions. Here, we reinvestigated role UCB. knockout reduced phenotype m6A levels UCB cell lines. However, complete depletion METTL3/m6A not achieved due selection cells expressing alternative isoforms. Systematic vulnerability inhibitor response analyses...
Oxidative stress promotes T . cruzi growth and development of chronic Chagas heart dysfunction. However, the literature contains gaps that must be fulfilled, largely due to variations in parasite DTU sources, cell types, mouse strains, tools manipulate redox status. We assessed impact oxidative environment on burden cardiomyoblasts effects Nrf2-inducer COPP function BALB/c mice infected with either DTU-II Y or DTU-I Colombian strains. Treatment antioxidants CoPP, apocynin, resveratrol,...
Epigenetic mechanisms are responsible for a wide range of biological phenomena in insects, controlling embryonic development, growth, aging and nutrition. Despite this, the role epigenetics shaping insect-pathogen interactions has received little attention. Gene expression eukaryotes is regulated by histone acetylation/deacetylation, an epigenetic process mediated acetyltransferases (HATs) deacetylases (HDACs). In this study, we explored Aedes aegypti acetyltransferase CBP (AaCBP) after...
Abstract Epigenetic mechanisms are responsible for a wide range of biological phenomena in insects, controlling embryonic development, growth, aging and nutrition. Despite this, the role epigenetics shaping insect-pathogen interactions has received little attention. Gene expression eukaryotes is regulated by histone acetylation/deacetylation, an epigenetic process mediated acetyltransferases (HATs) deacetylases (HDACs). In this study, we explored Aedes aegypti acetyltransferase CBP (AaCBP)...
Abstract Treatment and control of schistosomiasis still rely on only one effective drug, praziquantel (PZQ), due to mass treatment, the increasing risk selecting for schistosome strains that are resistant PZQ has alerted investigators urgent need develop novel therapeutic strategies. The histone-modifying enzymes (HMEs) represent promising targets development epigenetic drugs against Schistosoma mansoni . In present study, we targeted S. lysine-specific demethylase 1 (SmLSD1), a...