A5014242942- Parasitic Infections and Diagnostics
- Amoebic Infections and Treatments
- Viral gastroenteritis research and epidemiology
- Clostridium difficile and Clostridium perfringens research
- Pancreatitis Pathology and Treatment
- Cytomegalovirus and herpesvirus research
- Diagnosis and treatment of tuberculosis
- Cancer-related molecular mechanisms research
- SARS-CoV-2 and COVID-19 Research
- Plant and Fungal Interactions Research
- Viral Infections and Immunology Research
- Orthopedic Infections and Treatments
- CRISPR and Genetic Engineering
- SARS-CoV-2 detection and testing
- COVID-19 epidemiological studies
- Genomics and Phylogenetic Studies
- Coccidia and coccidiosis research
- Bacterial Identification and Susceptibility Testing
- Family and Patient Care in Intensive Care Units
- vaccines and immunoinformatics approaches
- Kruppel-like factors research
- Phagocytosis and Immune Regulation
- Parasites and Host Interactions
- Pediatric Hepatobiliary Diseases and Treatments
- Virology and Viral Diseases
The Francis Crick Institute
2020-2024
University of Pennsylvania
2019-2022
South University
2019-2021
University College London Hospitals NHS Foundation Trust
2020
University College London
2020
National Hospital for Neurology and Neurosurgery
2020
Philadelphia University
2020
University of Georgia
2015-2017
University of Vermont
2009-2016
The apicomplexan parasite Cryptosporidium is a leading global cause of severe diarrhoeal disease and an important contributor to early childhood mortality. Currently, there are no fully effective treatments or vaccines available. Parasite transmission occurs through ingestion oocysts, either direct contact consumption contaminated water food. Oocysts meiotic spores the product sex. has single-host life cycle in which both asexual sexual processes occur intestine infected hosts. Here, we...
Cryptosporidiosis, a diarrheal disease usually caused by Cryptosporidium parvum or hominis in humans, can result fulminant diarrhea and death AIDS patients chronic infection stunting children. Nitazoxanide, the current standard of care, has limited efficacy children is no more effective than placebo with advanced AIDS. Unfortunately, lack financial incentives technical difficulties associated working parasites have crippled efforts to develop treatments. In order address these obstacles, we...
Cryptosporidium is a leading cause of diarrheal disease and an important contributor to early childhood mortality, malnutrition, growth faltering. Older children in high endemicity regions appear resistant infection, while previously unexposed adults remain susceptible. Experimental studies humans animals support the development resistance, but we do not understand mechanisms that underlie protective immunity Cryptosporidium. Here, derive vivo model infection immunocompetent C57BL/6 mice by...
The apicomplexan parasite Cryptosporidium is a leading global cause of severe diarrheal disease and an important contributor to early-childhood mortality. Waterborne outbreaks occur frequently, even in countries with advanced water treatment capabilities, there currently no fully effective treatment. Nucleotide pathways are attractive targets for antimicrobial development, several laboratories designing inhibitors these enzymes as potential infections. Here we take advantage newly available...
Significance The intestinal immune system is able to control pathogens while tolerating and interpreting microbial cues from an abundant microbiome. mechanisms of innate recognition are crucial differentiating between pathogen commensal in this tissue mounting appropriate inflammatory response. Persistent inflammation can alter the cellular architecture physiology gut have lasting impact on nutritional state children who face frequent infection with certain enteric pathogens. We demonstrate...
Cryptosporidiosis is a leading cause of waterborne diarrheal disease globally and an important contributor to mortality in infants the immunosuppressed. Despite its importance, Cryptosporidium community has only had access good, but incomplete, parvum IOWA reference genome sequence. Incomplete sequences hamper annotation, experimental design, interpretation. We have generated new C. assembly supported by Pacific Biosciences (PacBio) Oxford Nanopore long-read technologies comparative...
Abstract The apicomplexan parasite Cryptosporidium is a leading cause of diarrheal disease and an important contributor to overall global child mortality. We currently lack effective treatment immune prophylaxis. Recent advances now permit genetic modification this pathogen. expect produce rapid in fundamental as well translational research on cryptosporidiosis. Here we outline engineering for sufficient detail establish transfection any laboratory that requires access key technology. This...
The parasite Cryptosporidium is responsible for diarrheal disease in young children causing death, malnutrition, and growth delay. invades enterocytes where it develops a unique intracellular niche. Infected cells exhibit profound changes morphology, physiology, transcriptional activity. How the effects these poorly understood. We explored localization of highly polymorphic proteins found members parvum MEDLE protein family to be translocated into cytosol infected cells. All life stages...
Cryptosporidium is a leading cause of severe diarrhea and diarrheal-related death in children worldwide. As an obligate intracellular parasite, relies on intestinal epithelial cells to provide niche for its growth survival, but little known about the contributions that infected cell makes this relationship. Here we conducted genome wide CRISPR/Cas9 knockout screen discover host genes influence parvum infection and/or survival. Gene enrichment analysis indicated interferon response,...
Cryptosporidium is a common intestinal infection of vertebrates and significant threat to public health. Within the epithelial layer intestine, parasite invades replicates. Infected cells are readily detected under microscope by presence elongated microvilli, particularly around vacuole where resides. Here, we identify family virulence factors that exported into host cell during localise microvilli. We examine trafficking function most highly expressed member, MVP1, which appears control...
Cryptosporidium is a protist parasite that has been identified as the second leading cause of moderate to severe diarrhea in children younger than two and significant mortality worldwide. complex, obligate, intracellular but extra cytoplasmic lifecycle single host. How genes are regulated this remains largely unknown. Long non-coding RNAs (lncRNAs) play critical regulatory roles, including gene expression across broad range organisms. lncRNAs have reported enter host cell nucleus affect...
ABSTRACT Invasive amebiasis due to Entamoeba histolytica infection is an important cause of morbidity in developing countries. The E. genome contains two homologues the metalloprotease leishmanolysin gene, MSP-1 ( EhMSP-1 ) and EhMSP-2 , while commensal ameba dispar has lost . In this study, we sought characterize metallosurface protease 1 (EhMSP-1). Using immunoprecipitation a model substrate, found that was functional metalloprotease. Confocal microscopy flow cytometry revealed localized...
The intestinal protozoan Cryptosporidium is a leading cause of diarrheal disease and mortality in young children. There currently no fully effective treatment for cryptosporidiosis, which has stimulated interest anticryptosporidial development over the last ∼10 years, with numerous lead compounds identified, including several tRNA synthetase inhibitors. Here, we report results dairy calf efficacy trial methionyl-tRNA (Cryptosporidium parvum MetRS [CpMetRS]) inhibitor 2093 spontaneous...
Cryptosporidium is a leading cause of diarrheal-related deaths in children, especially resource-poor settings. It also targets the immunocompromised, chronically infecting people living with HIV and primary immunodeficiencies. There no vaccine or effective treatment. Although it known from human cases animal models that CD4+ T cells play role curbing Cryptosporidium, CD8+ remains to be defined. Using tyzzeri mouse model, we show gut-resident intraepithelial lymphocytes (IELs) confer...
The protozoan parasite Entamoeba histolytica is responsible for invasive intestinal and extraintestinal amebiasis. virulence of strongly correlated with the parasite's capacity to effectively kill phagocytose host cells. process by which cells are killed phagocytosed follows a sequential model adherence, cell killing, initiation phagocytosis, engulfment. This paper presents recent advances in cytolytic phagocytic processes context model.
To identify potential opportunities for drug repurposing by developing an automated approach to pre-screen the predicted proteomes of any organism against databases known targets using only freely available resources.We employed a combination Ruby scripts that leverage data from DrugBank and ChEMBL databases, MySQL, BLAST predict drugs their 13 published genomes. Results previous cell-based screen inhibitors Cryptosporidium parvum growth were used validate our in-silico prediction...
What Is Cryptosporidium?Cryptosporidium infection, or cryptosporidiosis, was first described in mice by Ernest Tyzzer 1907, yet infection of humans went unrecognized until 1976 [1,2].The emergence HIV brought human cryptosporidiosis to the fore, 1980s, as a chronic and life threatening opportunistic infection.Most recently, series epidemiological studies have revealed truly ubiquitous nature its massive impact on global public health.Young children are highly susceptible one recent...
ABSTRACT The parasitic protozoan Entamoeba histolytica is aptly named for its capacity to destroy host tissue. When E. trophozoites invade the lamina propria of a colon, extracellular matrices are degraded while cells killed and phagocytosed. ability phagocytose correlates with virulence in vivo . In order better understand mechanism phagocytosis, we used an Affymetrix microarray chip measure total gene expression phagocytic nonphagocytic subpopulations. Using paramagnetic beads coated known...
Entamoeba histolytica is the protozoan parasite that causes invasive amebiasis, which endemic to many developing countries and characterized by dysentery liver abscesses. The virulence of E. correlates with degree host cell engulfment, or phagocytosis, phagocytosis alters amebic gene expression in a feed-forward manner results an increased phagocytic ability. Here, we used streamlined RNA interference screen silence 15 genes whose was upregulated trophozoites determine whether these actually...