Christoph Grevelding

University of Giessen | JLU · Institute of Parasitology

Studies on transcription regulation in platyhelminth development are scarce, especially for parasitic flatworms. Here, we employed single-cell transcriptomics to identify genes involved in reproductive development in the trematode model Schistosoma mansoni. This parasite causes schistosomiasis, a major neglected infectious disease affecting >240 mi...

Background Schistosoma mansoni was introduced from Africa to the Americas during the transatlantic slave trade and remains a major public health problem in parts of South America and the Caribbean. This study presents a comprehensive comparative analysis of three S. mansoni strains with different geographical origins—from Liberia, Belo Horizonte an...

Schistosomiasis affects over 250 million people worldwide, with the highest prevalence at the age of 10–14 years. The influence of the host’s age on the severity of liver damage is unclear. We infected male 8, 14, and 20-week-old mice with S. mansoni. Hepatic damage, inflammation, fibrosis, and metabolism were analyzed by RT-qPCR, Western blotting,...

Schistosomiasis, a parasitic disease caused by Schistosoma spp., affects more than 250 million people worldwide. S. mansoni in particular affects the gastrointestinal tract and, through its eggs, induces a Th2 immune response leading to granuloma formation. The relationship between egg load and immune response is poorly understood. We investigated...

Introduction Schistosomiasis has for many years relied on a single drug, praziquantel (PZQ) for treatment of the disease. Immense efforts have been invested in the discovery of protein kinase (PK) inhibitors; however, given that the majority of PKs are still not targeted by an inhibitor with a useful level of selectivity, there is a compelling need...

Schistosomiasis is a neglected tropical disease caused by worm parasites of the genus Schistosoma. Upon infection, parasite eggs can lodge inside of host organs like the liver. This leads to granuloma formation, which is the main cause of the pathology of schistosomiasis. To better understand the different levels of host–pathogen interaction and pa...

Schistosomiasis, a widespread neglected tropical disease, presents a complex and multifaceted clinical-pathological profile. Using hamsters as final hosts, we dissected molecular events following Schistosoma mansoni infection in the liver - the organ most severely affected in schistosomiasis patients. Employing TMT-based proteomics, we studied alte...

In this study, we employed a total of eight distinct modifications of histone proteins (H3K23ac, H3K27me3, H3K36me3, H3K4me3, H3K9ac, H3K9me3, H4K12ac, and H4K20me1) to discern the various chromatin colors encompassing lncRNA genes in both mature and immature gonads of the human parasite Schistosoma mansoni . Our investigation revealed that these c...

Schistosomes are parasitic flatworms that cause schistosomiasis, a neglected tropical disease of worldwide importance. Since standard treatment of schistosomiasis relies on a single drug, praziquantel, alternative drugs are needed. G protein-coupled receptors (GPCRs) represent promising targets for new anthelmintics. Although GPCRs represent a prom...

Schistosomiasis is a parasitic disease affecting more than 250 million people worldwide. The transcription factor c-Jun, which is induced in S. mansoni infection-associated liver disease, can promote hepatocyte survival but can also trigger hepatocellular carcinogenesis. We aimed to analyze the hepatic role of c-Jun following S. mansoni infection....

Recently, we reported programmed Cas9 mediated insertion of a reporter gene into a gene safe harbor site, GSH1, of Schistosoma mansoni via homology-directed repair (HDR) using overlapping guide RNAs. Here, we report efficient and precise CRISPR/Cas12a-mediated homology directed insertion (knockin, KI) of a 5’ C6-PEG10-modified double-stranded trans...

Recently, we reported programmed Cas9 mediated insertion of a reporter gene into a gene safe harbor site, GSH1, of Schistosoma mansoni via homology-directed repair (HDR) using overlapping guide RNAs. Here, we report efficient and precise CRISPR/Cas12a-mediated homology-directed insertion of a 5’ C6-PEG10-modified double-stranded transgene bearing m...

Background & aims: Schistosomiasis is one of the most prominent parasite-induced infectious diseases affecting more than 250 million people. S. mansoni causes metabolic exhaustion and a strong redox imbalance in the liver causing parenchymal damage and may predispose for cancer. We investigated, whether oxidative stress provokes hepatocellular pro...

The identification and characterization of genomic safe harbor sites (GSHs) can facilitate consistent transgene activity with minimal disruption to the host cell genome. We combined computational genome annotation and chromatin structure analysis to predict the location of four GSHs in the human blood fluke, Schistosoma mansoni, a major infectious...

In parasites such as Schistosoma mansoni, gene knockdown by RNA interference (RNAi) has become an indispensable tool for functional gene characterization. To distinguish target-specific RNAi effects versus off-target effects, controls are essential. To date, however, there is still no general agreement about suitable RNAi controls, which limits the...

Inhibition of eukaryotic initiation factor 4A has been proposed as a strategy to fight pathogens. Rocaglates exhibit the highest specificities among eIF4A inhibitors, but their anti-pathogenic potential has not been comprehensively assessed across eukaryotes. In silico analysis of the substitution patterns of six eIF4A1 aa residues critical to roca...

Introduction Schistosomes are the only mammalian flatworms that have evolved separate sexes. A key question of schistosome research is the male-dependent sexual maturation of the female since a constant pairing contact with a male is required for the onset of gonad development in the female. Although this phenomenon is long known, only recently a f...

Schistosomiasis is an infectious disease caused by blood flukes of the genus Schistosoma and affects approximately 200 million people worldwide. Since Praziquantel (PZQ) is the only drug for schistosomiasis, alternatives are needed. By a biochemical approach, we identified a tegumentally expressed aldehyde dehydrogenase (ALDH) of S. mansoni, SmALDH...

Schistosomiasis or bilharzia is caused by blood flukes of the genus Schistosoma and represents a considerable health and economic burden in tropical and subtropical regions. The treatment of this infectious disease relies on one single drug: praziquantel (PZQ). Therefore, new and potent antischistosomal compounds need to be developed. In our previo...

Background & Aims Schistosomiasis, is a parasitic infection, which globally affects more than 200 million people. Schistosome eggs, but not the adult worms, are mainly responsible for schistosomiasis-specific morbidity in the liver. It is unclear if S. mansoni eggs consume host metabolites, and how this compromises the host parenchyma. Methods Met...

Selective inhibition of eukaryotic initiation factor 4A (eIF4A), an RNA helicase, has been proposed as a strategy to fight pathogens. Plant-derived rocaglates exhibit some of the highest specificities among eIF4A inhibitors. Sensitivity to rocaglates is determined by key amino acid (aa) residues mediating reversible clamping of the eIF4A:RNA comple...

The identification and characterization of genomic safe harbor sites (GSH) aims to facilitate consistent transgene activity without disruption to the host cell genome. We combined genome annotation and chromatin structure analysis by computational approach to predict the location of four GSHs in the human blood fluke, Schistosoma mansoni , a major...

Schistosomiasis is a neglected tropical disease with more than 200 million new infections per year. It is caused by parasites of the genus Schistosoma and can lead to death if left untreated. Currently, only two drugs are available to combat schistosomiasis: praziquantel and, to a limited extent, oxamniquine. However, the intensive use of these two...

Understanding drug penetration, distribution, and metabolization is fundamental for understanding drug efficacy. This also accounts for parasites during antiparasitic treatment. Recently, we established matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) in blood flukes and liver flukes. This label-free technique is...

Schistosomiasis, caused by the human parasite Schistosoma mansoni , is one of the WHO-listed neglected tropical diseases (NTDs), and it has severe impact on morbidity and mortality, especially in Africa. Not only the adult worms but also their eggs are responsible for health problems. Up to 50% of the eggs produced by the female worms are not excre...

Schistosomiasis is a neglected tropical disease affecting more than 200 million people worldwide. Chemotherapy relies on one single drug, praziquantel, which is safe but ineffective at killing larval stages of this parasite. Furthermore, concerns have been expressed about the rise in resistance against this drug. In the absence of an antischistosom...

Schistosomiasis, caused by schistosome parasites, is a neglected tropical disease affecting humans and animals. There is no vaccine available yet, and fear of upcoming resistance against the only widely used drug, praziquantel, is omnipresent. Previously, we showed that imatinib (Gleevec), an anticancer drug, affected schistosome physiology and cau...

A large portion of animal and plant genomes consists of non-coding DNA. This part includes tandemly repeated sequences and gained attention because it offers exciting insights into genome biology. We investigated satellite-DNA elements of the platyhelminth Schistosoma mansoni, a parasite with remarkable biological features. S. mansoni lives in the...

Schistosomiasis is a neglected tropical disease caused by blood flukes of the genus Schistosoma and causes severe morbidity in infected patients. In 2018, 290.8 million people required treatment, and 200,000 deaths are reported per year. Treatment of this disease depends on a single drug, praziquantel (PZQ). However, in the past few years, reduced...

Schistosomiasis is one of the most prominent parasite-induced infectious diseases, causing tremendous medical and socioeconomic problems. Current studies have reported on the spread of endemic regions and the fear of development of resistance against praziquantel, the only effective drug available. Among the Schistosoma species, only S. haematobium...

Background The heterologous expression of parasitic proteins is challenging because the sequence composition often differs significantly from host preferences. However, the production of such proteins is important because they are potential drug targets and can be screened for interactions with new lead compounds. Here we compared two expression sy...

Protein kinases are known as key molecules that regulate many biological processes in animals. The right open reading frame protein kinase (riok) genes are known to be essential regulators in model organisms such as the free-living nematode Caenorhabditis elegans. However, very little is known about their function in parasitic trematodes (flukes)....

Schistosoma mansoni is a parasitic flatworm causing schistosomiasis, an infectious disease affecting several hundred million people worldwide. Schistosomes live dioeciously, and upon pairing with the male, the female starts massive egg production, which causes pathology. Praziquantel (PZQ) is the only drug used, but it has an inherent risk of resis...

Schistosomiasis is a disease of global importance caused by parasitic flatworms, schistosomes, which cause pathogenicity through eggs laid by the female worm inside the host’s blood vessels. Maintenance of cellular homeostasis is crucial for parasites, as for other organisms, and is quite likely important for schistosome reproduction and vitality....

Schistosomiasis (bilharzia) is a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma, with considerable morbidity in parts of the Middle East, South America, Southeast Asia, in sub-Saharan Africa, and particularly also in Europe. The WHO describes an increasing global health burden with more than 290 million people thr...

Helminths such as the blood fluke Schistosoma mansoni represent a major global health challenge due to limited availability of drugs. Most anthelminthic drug candidates are derived from plants, whereas insect-derived compounds have received little attention. This includes venom from assassin bugs, which contains numerous bioactive compounds. Here,...

Schistosomes are the causative agent of schistosomiasis, which affects more than 200 million people worldwide. Unlike other trematode parasites, schistosomes (along with the Didymozoidae) have evolved separate sexes. Pairing of males and females is a prerequisite for female sexual development and subsequent egg production. However, the mechanisms u...

Schistosomes are human pathogens causing the neglected tropical disease schistosomiasis, which occurs worldwide in (sub-)tropical regions. This infectious disease is often associated with poverty, and more than 700 million people are at risk of infection. Exploitation of novel habitats and limited therapeutic options brought schistosomes into resea...

Schistosomiasis is an acute and chronic disease caused by parasitic worms of the genus Schistosoma . Treatment is solely dependent on praziquantel. In the face of the worldwide dimension, projects have been initiated to develop new chemotherapies. Due to their proven druggability, G protein-coupled receptors (GPCRs) are promising targets for anthel...

Schistosomiasis is a neglected disease of poverty that is caused by several species of the trematode flatworm, Schistosoma. Treatment relies on just one drug, the pyrazinoisoquinoline, praziquantel (PZQ). PZQ has a number of pharmaceutical and pharmacological problems that encourage the search for new drugs. Focusing on the period 2015–2017, and in...

The parasitic disease schistosomiasis is the cause of more than 200 000 human deaths per year. Although the disease is treatable, there is one major shortcoming: praziquantel has been the only drug used to combat these parasites since 1977. The risk of the emergence of resistant schistosomes is known to be increasing, as a reduced sensitivity of th...

Schistosomes are the only platyhelminths that have evolved separate sexes, and they exhibit a unique reproductive biology because the female’s sexual maturation depends on a constant pairing contact with the male. In the female, pairing leads to gonad differentiation, which is associated with substantial morphological changes, and controls among ot...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Facilitated by the Schistosoma mansoni genome project, multiple transcriptomic studies were performed over the last decade to elucidate gene expression patterns among different developmental stages of the complex schistosome life cycle. While these analyses enable the identification of candidate genes with key functions in schistosome biology, a di...