A5052828429- Malaria Research and Control
- Mosquito-borne diseases and control
- Complement system in diseases
- Invertebrate Immune Response Mechanisms
- HIV Research and Treatment
- Vector-borne infectious diseases
- American Constitutional Law and Politics
- European Political History Analysis
- Traumatic Brain Injury and Neurovascular Disturbances
- CRISPR and Genetic Engineering
- vaccines and immunoinformatics approaches
- Reformation and Early Modern Christianity
- Computational Drug Discovery Methods
- Aquaculture disease management and microbiota
- Traumatic Brain Injury Research
- Global Financial Crisis and Policies
- Trypanosoma species research and implications
- Bacteriophages and microbial interactions
- Economic Theory and Policy
- Drug Transport and Resistance Mechanisms
- Coccidia and coccidiosis research
- Parasitic Infections and Diagnostics
- Economic Theory and Institutions
- Hepatitis B Virus Studies
- Toxoplasma gondii Research Studies
Center for Global Health
2016-2025
University of South Florida
2016-2025
Mahidol Oxford Tropical Medicine Research Unit
2024-2025
Mahidol University
2024-2025
Vanderbilt University
2025
Florida College
2011-2023
University of Calabar
2022
Texas A&M University
2005-2021
University of Tampa
2020
Griffith University
1989-2017
Severe malaria is caused by the apicomplexan parasite Plasmodium falciparum. Despite decades of research, distinct biology these parasites has made it challenging to establish high-throughput genetic approaches identify and prioritize therapeutic targets. Using transposon mutagenesis P. falciparum in an approach that exploited its AT-rich genome, we generated more than 38,000 mutants, saturating genome defining mutability fitness costs for over 87% genes. Of 5399 genes, our study defined...
The human malaria parasite Plasmodium vivax is responsible for 25–40% of the ∼515 million annual cases worldwide. Although seldom fatal, elicits severe and incapacitating clinical symptoms often causes relapses months after a primary infection has cleared. Despite its importance as major pathogen, P. little studied because it cannot be propagated continuously in laboratory except non-human primates. We sequenced genome to shed light on distinctive biological features, means drive development...
Malaria erythrocyte binding proteins use the Duffy blood group antigen (Plasmodium vivax and Plasmodium knowlesi) sialic acid falciparum) on surface as receptors. We had previously cloned one P. gene, falciparum part of three knowlesi genes encoding these described homology between genes. have completed cloning sequencing identified introns in that correct published deduced amino sequences. All similar structures, with or two exons signal sequence domain, an exon transmembrane cytoplasmic...
A major cause of the paucity new starting points for drug discovery is lack interaction between academia and industry. Much global resource in biology present universities, whereas focus medicinal chemistry still largely within Open source discovery, with sharing information, clearly a first step towards overcoming this gap. But interface could especially be bridged through scale-up open physical compounds, which would accelerate finding discovery. The Medicines Malaria Venture Box...
Transmission represents a population bottleneck in the Plasmodium life cycle and key intervention target of ongoing efforts to eradicate malaria. Sexual differentiation is essential for this process, as only sexual parasites, called gametocytes, are infective mosquito vector. Gametocyte production rates vary depending on environmental conditions, but external stimuli remain obscure. Here, we show that host-derived lipid lysophosphatidylcholine (LysoPC) controls P. falciparum cell fate by...
The ultrastructural features of cerebral contusion seen three hours to 11 days after head injury were studied in 18 patients undergoing surgery. Massive astrocytic swelling ("cytotoxic" oedema) was injury, maximal perivascular foot processes, and compressing some the underlying capillaries. tight junctions not disrupted. Neuronal damage most marked injury. pathophysiological mechanisms leading oedema formation neuronal degeneration are discussed.
Background Plasmodium vivax invasion requires interaction between the human Duffy antigen on surface of erythrocytes and P. binding protein (PvDBP) expressed by parasite. Given that Duffy-negative individuals are resistant heterozygotes show reduced susceptibility to blood-stage infection, we hypothesized antibodies directed against region two (PvDBPII) would inhibit erythrocytes. Methods Findings Using a recombinant (rPvDBPII), polyclonal were generated from immunized rabbits affinity...
✓ A new model of traumatic axonal injury has been developed by causing a single, rapid, controlled elongation (tensile strain) in the optic nerve albino guinea pig. Electron microscopy demonstrates swelling, axolemmal blebs, and accumulation organelles identical to those seen human experimental brain injury. Quantitative morphometric studies confirm that 17% axons are injured without vascular disruption, horseradish peroxidase (HRP) alterations rapid axoplasmic transport at sites Since 95%...
Abstract Malaria liver stages represent an ideal therapeutic target with a bottleneck in parasite load and reduced clinical symptoms; however, current vitro pre-erythrocytic (PE) models for Plasmodium vivax P . falciparum lack the efficiency necessary rapid identification effective evaluation of new vaccines drugs, especially targeting late liver-stage development hypnozoites. Herein we report 384-well plate culture system using commercially available materials, including cryopreserved...
The malaria agent Plasmodium falciparum is predicted to export a “secretome” of several hundred proteins remodel the host erythrocyte. Prediction protein based on presence an ER-type signal sequence and downstream Host-Targeting (HT) motif (which similar to, but distinct from, closely related Export Element [PEXEL]). Previous attempts determine entire secretome, using either HT-motif or PEXEL, have yielded large sets proteins, which not been comprehensively tested. We present here expanded...
Plasmodium vivax (Pv) is a major cause of human malaria and increasing in public health importance compared with falciparum malaria. Pv unique among malarias that invasion erythrocytes almost solely dependent on the red cell's surface receptor, known as Duffy blood-group antigen (Fy). Fy an important minor has two immunologically distinct alleles, referred to or b , resulting from single-point mutation. This mutation occurs within binding domain parasite's cell ligand. Whether this...
Significance Plasmodium vivax is a causative agent of malaria that results in high morbidity and mortality. P. Duffy Binding Protein (PvDBP) leading vaccine candidate for ; however, PvDBP highly variable, which prevents strain transcending immune response, complicating design. Here we report the first, to our knowledge, broadly neutralizing antibody epitopes within PvDBP, expand known repertoire this protein. The identification conserved inhibitory provides critical new motifs should be...
CRISPR-Cas9 gene-editing technology has facilitated the generation of knockout mice, providing an alternative to cumbersome and time-consuming traditional embryonic stem cell-based methods. An earlier study reported up 16% efficiency in generating conditional (cKO or floxed) alleles by microinjection 2 single guide RNAs (sgRNA) single-stranded oligonucleotides as donors (referred herein "two-donor floxing" method).We re-evaluate two-donor method from a consortium 20 laboratories across...
ABSTRACT Long noncoding RNAs (LncRNAs) are increasingly recognized as being involved in human physiology and diseases, but there is a lack of mechanistic understanding for the majority lncRNAs. We comparatively tested proposed mechanisms antisense lncRNA regulation at X-chromosome Inactivation (XCI) locus. find that due to stochasticity transcription, different based on act transcription regulate Xist Tsix levels nascent transcription. At medium levels, RNA polymerases transcribe each strand...
Malaria parasites are highly divergent from model eukaryotes. Large-scale genome engineering methods effective in organisms frequently inapplicable, and systematic studies of gene function few. We generated more than 175,000 transposon insertions the Plasmodium knowlesi genome, averaging an insertion every 138 base pairs, used this “supersaturation” mutagenesis to score essentiality for 98% genes. The density mutations allowed mapping putative essential domains within genes, providing a...
Functional analysis of the Plasmodium falciparum genome is restricted because limited ability to genetically manipulate this important human pathogen. We have developed an efficient transposon-mediated insertional mutagenesis method much needed for high-throughput functional genomics malaria parasites. A drug-selectable marker, dihydrofolate reductase, added lepidopteran transposon piggyBac , transformed parasites by integration into P. in presence a transposase-expressing helper plasmid....