A5023260739- Malaria Research and Control
- Mosquito-borne diseases and control
- Complement system in diseases
- Drug Transport and Resistance Mechanisms
- Venomous Animal Envenomation and Studies
- HIV Research and Treatment
- vaccines and immunoinformatics approaches
- Invertebrate Immune Response Mechanisms
- Blood Coagulation and Thrombosis Mechanisms
- RNA and protein synthesis mechanisms
- Parasites and Host Interactions
- Monoclonal and Polyclonal Antibodies Research
- Computational Drug Discovery Methods
- Genetics, Bioinformatics, and Biomedical Research
- Cell Adhesion Molecules Research
- Trypanosoma species research and implications
- Platelet Disorders and Treatments
- Viral Infections and Immunology Research
- DNA and Nucleic Acid Chemistry
- Aquaculture disease management and microbiota
- Peptidase Inhibition and Analysis
- Genomics and Phylogenetic Studies
- Lipid Membrane Structure and Behavior
- Research on Leishmaniasis Studies
- Neuroinflammation and Neurodegeneration Mechanisms
Liverpool School of Tropical Medicine
2015-2024
University of Oxford
1990-2023
Centre for Human Genetics
2023
University of Liverpool
2006-2021
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
2008-2021
Umm al-Qura University
2016
John Radcliffe Hospital
1991-2015
University of Malawi
2008
University of North Carolina at Chapel Hill
2008
The Royal Melbourne Hospital
2008
A major part of virulence for Plasmodium falciparum malaria infection, the most lethal parasitic disease humans, results from increased rigidity and adhesiveness infected host red cells. These changes are caused by parasite proteins exported to erythrocyte using novel trafficking machinery assembled in cell. To understand these unique modifications, we used a large-scale gene knockout strategy combined with functional screens identify into parasite-infected erythrocytes involved remodeling...
The integrin lymphocyte function-associated antigen-1 (LFA-1) expressed on T cells serves as a useful model for analysis of leukocyte functional activity. We have assessed the role divalent cations Mg2+, Ca2+, and Mn2+ in LFA-1 binding to ligand intercellular adhesion molecule-1 (ICAM-1) induction cation-dependent epitope recognized by mAb 24. Manganese strongly promoted both expression 24 cell ICAM-1 via LFA-1, suggesting that is able directly alter conformation manner favors binding. Since...
In light of the recent controversies over role animal models for research into development new treatments severe malaria, particularly cerebral disease, a group scientists came together to discuss relative merits range and their overlap with complex clinical syndromes human disease.While it was not possible fully resolve differences utility Plasmodium berghei ANKA model experimental meeting did bring two communities closer identify further work provide information needed validate revitalise...
MalariaGEN is a data-sharing network that enables groups around the world to work together on genomic epidemiology of malaria. Here we describe new release curated genome variation data 7,000 Plasmodium falciparum samples from partner studies in 28 malaria-endemic countries. High-quality genotype calls 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using standardised analysis pipeline. Copy number variants associated with drug resistance structural cause...
<ns3:p>We describe the MalariaGEN Pf7 data resource, seventh release of <ns3:italic>Plasmodium falciparum</ns3:italic> genome variation from network. It comprises over 20,000 samples 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented. For first time we include dried blood spot sequenced after selective whole amplification, necessitating new methods to genotype copy number variations. We identify a large newly emerging...
One important factor in the virulence of infections with Plasmodium falciparum is adherence infected erythrocytes to small vessel endothelium. In that lead serious, life-threatening disease accumulation large numbers cells particular organs thought organ dysfunction or failure. This relevance when affected brain, leading development cerebral malaria. Many different endothelial receptors for red blood have been identified. Some such as CD36 and thrombospondin are used by all parasite...
Binding of infected erythrocytes to brain venules is a central pathogenic event in the lethal malaria disease complication, cerebral malaria. The only parasite adhesion trait linked sequestration binding intercellular molecule-1 (ICAM-1). In this report, we show that Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) binds ICAM-1. We have cloned and expressed PfEMP1 recombinant proteins from A4tres parasite. Using heterologous expression mammalian cells, minimal ICAM-1 domain was...
The malarial parasite Plasmodium falciparum has acted as a potent selective force on the human genome. particular virulence of this organism is thought to be due adherence parasitised red blood cells small vessel endothelium through several receptors, including CD36, thrombospondin and intercellular adhesion molecule 1 (ICAM-1, CD54), isolates differ in their ability bind each. Immunohistochemical studies have implicated ICAM-1 potential importance pathogenesis cerebral malaria, leading us...
Summary. Adhesion of parasitized erythrocytes to microvascular endothelium is a central event in the pathogenesis severe falciparum malaria. We have characterized adhesion flowing red blood cells three known endothelial receptors coated on plastic surfaces (CD36, intercellular molecule‐1 (ICAM‐1) and thrombospondin (TSP)), also bearing these (human umbilical vein (HUVEC) platelets). All could mediate at wall shear stress within physiological range. The great majority adherent formed rolling...
Our understanding of the basis severe disease in malaria is incomplete. It clear that pathology part related to pro-inflammatory nature host response but a number other factors are also thought be involved, including interaction between infected erythrocytes and endothelium. This complex system involving several receptors major parasite-derived variant antigen (PfEMP1) expressed on surface erythrocyte membrane. Previous studies have suggested role for ICAM-1 cerebral malaria, although these...
Report4 January 2019Open Access Transparent process Cerebral malaria is associated with differential cytoadherence to brain endothelial cells Janet Storm Corresponding Author [email protected] orcid.org/0000-0001-7812-4220 Department of Parasitology, Liverpool School Tropical Medicine, Liverpool, UK Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi College University Malawi, Search for more papers by this author Jakob S Jespersen orcid.org/0000-0002-4930-5900...
Abstract Cerebral Plasmodium falciparum malaria is characterized by adhesion of infected erythrocytes (IEs) to the cerebral microvasculature. This has been linked parasites expressing structurally related group A subset P. erythrocyte membrane protein 1 (PfEMP1) family IE ligands and IEs with affinity for ICAM-1. However, recent evidence cast doubt on both these associations, tempering hopes feasibility developing a vaccine based ICAM-1–binding PfEMP1. In this study, we report identification...
The interaction of lymphocyte function-associated antigen-1 (LFA-1) with its ligands mediates multiple cell adhesion processes capital importance during immune responses. We have obtained three anti-ICAM-3 mAbs which recognize two different epitopes (A and B) on the intercellular molecule-3 (ICAM-3) as demonstrated by sequential immunoprecipitation cross-competitive mAb-binding experiments. Immunoaffinity purified ICAM-3-coated surfaces were able to support T lymphoblast attachment upon...
We have compared the adhesion of Plasmodium falciparum-infected erythrocytes to human dermal microvascular endothelial cells (HDMEC) and umbilical vein (HUVEC) assessed relative roles receptors CD36 intercellular molecule-1 (ICAM-1). HUVEC (a cell line that expresses high levels ICAM-1 but no CD36) mediate low adhesion, whereas HDMEC (which constitutively express even before induction expression leads yet greater which are inhibited both by anti-ICAM-1 mAbs, despite increase in CD36. The...
Binding of fibrinogen to intercellular adhesion molecule 1 (ICAM-1) enhances leukocyte endothelium by acting as a bridging between the two cell types. Here, panel four monoclonal antibodies (mAbs) ICAM-1 was used dissect structure-function requirements this recognition. All mAbs bound transfectants and immunoprecipitated immunoblotted from detergent-solubilized JY lymphocyte extracts. Functionally, 1G12 2D5 inhibited binding 125I-fibrinogen ICAM-1-transfectants abrogated enhancing effect on...