A5054770590- Parasites and Host Interactions
- Parasite Biology and Host Interactions
- Trace Elements in Health
- Helminth infection and control
- CRISPR and Genetic Engineering
- Viral gastroenteritis research and epidemiology
- Child Nutrition and Water Access
- Extracellular vesicles in disease
- MicroRNA in disease regulation
- Parasitic Infections and Diagnostics
- Transplantation: Methods and Outcomes
- Digestive system and related health
- Helicobacter pylori-related gastroenterology studies
- Parasitic Diseases Research and Treatment
- Trypanosoma species research and implications
- Mollusks and Parasites Studies
- Malaria Research and Control
- Oral and gingival health research
- Iron Metabolism and Disorders
- Research on Leishmaniasis Studies
- Organ Transplantation Techniques and Outcomes
- Parasitic infections in humans and animals
- Infant Nutrition and Health
- HIV Research and Treatment
- Liver physiology and pathology
George Washington University
2015-2025
Washington University Medical Center
2009-2018
Washington University in St. Louis
2011
Tulane University
2000-2009
University Hospital and Clinics
2000
QIMR Berghofer Medical Research Institute
1996-2000
The University of Queensland
2000
University Medical Center
2000
Food borne trematodes (FBTs) are an assemblage of platyhelminth parasites transmitted through the food chain, four which recognized as neglected tropical diseases (NTDs). Fascioliasis stands out among other NTDs due to its broad and significant impact on both human animal health, Fasciola sp., also considered major pathogens domesticated ruminants. Here we present a reference genome sequence common liver fluke, hepatica isolated from sheep, complementing previously reported isolate cattle. A...
CRISPR/Cas9-based genome editing has yet to be reported in species of the Platyhelminthes. We tested this approach by targeting omega-1 (ω1) Schistosoma mansoni as proof principle. This secreted ribonuclease is crucial for Th2 polarization and granuloma formation. Schistosome eggs were exposed Cas9 complexed with guide RNA complementary ω1 electroporation or transduction lentiviral particles. Some also transfected a single stranded donor template. Sequences amplicons from gene-edited...
Infection with the food-borne liver fluke Opisthorchis viverrini is principal risk factor (IARC Working Group on Evaluation of Carcinogenic Risks to Humans, 2012) for cholangiocarcinoma (CCA) in Lower Mekong River Basin countries including Thailand, Lao PDR, Vietnam and Cambodia. We exploited this link explore role secreted growth termed granulin (Ov-GRN-1) pre-malignant lesions by undertaking programmed CRISPR/Cas9 knockout Ov-GRN-1 gene from genome. Deep sequencing amplicon libraries...
Functional studies will facilitate characterization of role and essentiality newly available genome sequences the human schistosomes, Schistosoma mansoni, S. japonicum haematobium. To develop transgenesis as a functional approach for these pathogens, we previously demonstrated that pseudotyped murine leukemia virus (MLV) can transduce schistosomes leading to chromosomal integration reporter transgenes short hairpin RNA cassettes. Here investigated vertical transmission through developmental...
α-galactosidase (α-GAL) and α-N-acetylgalactosaminidase (α-NAGAL) are two glycosyl hydrolases responsible for maintaining cellular homeostasis by regulating glycan substrates on proteins lipids. Mutations in the human genes encoding either enzyme lead to neurological neuromuscular impairments seen both Fabry- Schindler/Kanzaki- diseases. Here, we investigate whether parasitic blood fluke Schistosoma mansoni , neglected tropical disease schistosomiasis, also contains functionally important...
<title>Abstract</title> <bold>Objectives</bold>. Sensitive diagnostics are needed to improve management and surveillance of opisthorchiasis opisthorchiasis-associated cholangiocarcinoma (CCA), given the major public health problem this condition in East Asia. We aimed screen Opisthorchis viverrini recombinant proteome identity antibody biomarkers liver fluke infection fluke-associated CCA with sera from study participants endemic populations evaluate their utility as point-of-care...
The liver fluke Opisthorchis viverrini is classified as a class I carcinogen due to the association between cholangiocarcinoma and chronic O. infection. During its feeding activity within bile duct, parasite secretes several cathepsin F cysteine proteases that may induce or contribute pathologies associated with hepatobiliary abnormalities.Here, we describe cDNA, gene organization, phylogenetic relationships, immunolocalization, functional characterization of protease gene, here termed...
Background Minimal information on the genome and proteome of Schistosoma haematobium is available, in marked contrast to situation with other major species human schistosomes for which draft sequences have been reported. Accordingly, little known about functional genomics S. haematobium, including utility or not RNA interference techniques that, if promise guide development new interventions schistosomiasis haematobia. Methods/Findings Here we isolated cultured developmental stages derived...
Infection with the food-borne liver fluke Opisthorchis viverrini is principal risk factor for cholangiocarcinoma (CCA) in Mekong Basin countries of Thailand, Lao PDR, Vietnam, Myanmar and Cambodia. Using a novel model CCA, involving infection gene-edited flukes hamster during concurrent exposure to dietary nitrosamine, we explored role granulin-like growth Ov -GRN-1 malignancy. We derived RNA-guided gene knockout ( ΔOv-grn-1) using CRISPR/Cas9/gRNA materials delivered by electroporation....
The schistosome egg represents an attractive developmental stage at which to target transgenes because of the high ratio germ somatic cells, transgene might be propagated and amplified by infecting snails with miracidia hatched from treated eggs, eggs can readily obtained experimentally infected rodents.We investigated utility square wave electroporation deliver other macromolecules including fluorescent (Cy3) short interference (si) RNA molecules, messenger RNAs, virions into Schistosoma...
The liver fluke Opisthorchis viverrini is a food-borne, zoonotic pathogen endemic to Thailand and adjacent counties in Southeast Asia. adult developmental stage of the O parasite excretes secretes numerous proteins within biliary tract including gall bladder. Lesions caused by feeding activities represent wounds that undergo protracted cycles healing re-injury over during chronic infection, which can last for decades. Components excretory/secretory (ES) complement released worms capably...
Genome sequences are available for the human blood flukes, Schistosoma japonicum, S. mansoni and haematobium. Functional genomic approaches could aid in identifying role importance of these newly described schistosome genes. Transgenesis is established functional genomics model species, which can lead to gain- or loss-of-functions, facilitate vector-based RNA interference, represents an effective forward genetics tool insertional mutagenesis screens. Progress toward routine transgenesis...
<ns4:p>Schistosomiasis is an important parasitic disease, touching roughly 200 million people worldwide. The causative agents are different <ns4:italic>Schistosoma</ns4:italic> species. Schistosomes have a complex life cycle, with freshwater snail as intermediate host. After infection, sporocysts develop inside the host and give rise to human dwelling larvae. We present here detailed step-by-step video instruction in English, French, Spanish Portuguese that shows how these can be manipulated...
Crosstalk between malignant and neighboring cells contributes to tumor growth. In East Asia, infection with the liver fluke is a major risk factor for cholangiocarcinoma (CCA). The Opisthorchis viverrini secretes growth termed granulin, homologue of human progranulin, which significantly biliary tract fibrosis morbidity. Here, extracellular vesicle (EV)-mediated transfer mRNAs from cholangiocytes naïve recipient was investigated following exposure granulin. To minimize influence endogenous...
ABSTRACT The microsporidian Vittaforma corneae has been reported as a pathogen of the human stratum corneum, where it can cause keratitis, and is associated with systemic infections. In addition to this direct role an infectious, etiologic agent disease, V. used model organism for another microsporidian, Enterocytozoon bieneusi , frequent problematic HIV‐infected patients that, unlike difficult maintain study in vitro. Unfortunately, few molecular sequences are available corneae. study,...
Draft genome sequences for Schistosoma japonicum and mansoni are now available. The schistosome encodes approximately 13,000 protein encoding genes which the function of only a small minority is understood. new represent potential intervention targets. Molecular tools needed to determine importance these genes. There role transgenesis in functional genomics gene sequences, both gain- loss-of-function approaches such as insertional mutagenesis screens vector-based RNA interference. This...
Schistosomiasis is the most important helminthic disease of humanity in terms morbidity and mortality. Facile manipulation schistosomes using lentiviruses would enable advances functional genomics these related neglected tropical diseases pathogens including tapeworms, their non-dividing cells. Such approaches have hitherto been unavailable. Blood stream forms human blood fluke, Schistosoma mansoni, causative agent hepatointestinal schistosomiasis, were infected with HIV-1 isolate NL4-3...
Septins are a family of eukaryotic GTP binding proteins conserved from yeasts to humans. Originally identified in mutants budding yeast, septins participate diverse cellular functions including cytokinesis, organization actin networks, cell polarity, vesicle trafficking and many others. assemble into heteroligomers form filaments rings. Here, four Schistosoma mansoni described, which appear be within the phylum Platyhelminthes. These orthologues were related SEPT5, SEPT10 SEPT7 humans, hence...