A5047220018- Malaria Research and Control
- Mosquito-borne diseases and control
- Drug Transport and Resistance Mechanisms
- Complement system in diseases
- HIV Research and Treatment
- Infective Endocarditis Diagnosis and Management
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Microbial Natural Products and Biosynthesis
- Synthesis and Catalytic Reactions
- Trypanosoma species research and implications
- Chemical Synthesis and Analysis
- Bacterial biofilms and quorum sensing
- Antimicrobial Resistance in Staphylococcus
- Invertebrate Immune Response Mechanisms
- Biomedical and Engineering Education
- Genetics, Bioinformatics, and Biomedical Research
- Hepatitis C virus research
- Gut microbiota and health
- Antifungal resistance and susceptibility
- RNA and protein synthesis mechanisms
- HIV/AIDS drug development and treatment
- Aquaculture disease management and microbiota
- Genomics and Phylogenetic Studies
- Drug-Induced Hepatotoxicity and Protection
- Hemoglobinopathies and Related Disorders
National University of Singapore
2013-2024
National University Health System
2022-2023
Singapore Centre for Environmental Life Sciences Engineering
2022-2023
Karolinska Institutet
2015-2021
The contribution of biofilms to virulence and as a barrier treatment is well-established for Staphylococcus aureus Enterococcus faecalis, both nosocomial pathogens frequently isolated from biofilm-associated infections. Despite frequent co-isolation, their interactions in have not been well-characterized. We report that combination, these two species can give rise augmented biomass dependent on the activation E. faecalis aerobic respiration. In respiration requires exogenous heme activate...
Enterococcus faecalis is an opportunistic pathogen that frequently co-isolated with other microbes in wound infections. While E. can subvert the host immune response and promote survival of via interbacterial synergy, little known about impact faecalis-mediated suppression on co-infecting microbes. We hypothesized attenuate neutrophil-mediated responses mixed-species infection to species. found neutrophils control phagocytosis, ROS production, degranulation azurophilic granules, but it does...
Several recent discoveries of the hallmark features programmed cell death (PCD) in Plasmodium falciparum have presented possibility revealing novel targets for antimalarial therapy. Using a combination cell-based assays, flow cytometry and fluorescence microscopy, we detected including mitochondrial dysregulation, activation cysteine proteases situ DNA fragmentation parasites induced with chloroquine (CQ) staurosporine (ST). The use pan-caspase inhibitor, z-Val-Ala-Asp-fmk (zVAD),...
The ABO blood group antigens are expressed on erythrocytes but also endothelial cells, platelets and serum proteins. Notably, the of a malaria patient determines development disease given that O reduces probability to succumb in severe malaria, compared individuals groups A, B or AB. P. falciparum rosetting sequestration mediated by PfEMP1, RIFIN STEVOR, at surface parasitized red cell (pRBC). Antibodies these consequently modify course infection preventing promoting phagocytosis pRBC. Here...
Having previously characterized chloroquine (CQ)-induced programmed cell death (PCD) hallmarks in the malaria parasite Plasmodium falciparum and delineating a pathway linking these features, roles of non-classical mediators were investigated this paper. It was shown that later stages are Ca2+-dependent transcriptionally regulated. Moreover, it demonstrated for first time micromolar concentrations CQ partially permeabilized parasite's digestive vacuole (DV) membrane important upstream event...
An alternative antimalarial pathway of an ‘outdated’ drug, chloroquine (CQ), may facilitate its return to the shrinking list effective antimalarials. Conventionally, CQ is believed interfere with hemozoin formation at nanomolar concentrations, but resistant parasites are able efflux this drug from digestive vacuole (DV). However, we show that DV membrane both and sensitive laboratory field compromised after exposure micromolar concentrations CQ, leading extrusion proteases. Furthermore, only...
Due to the widespread prevalence of resistant parasites, chloroquine (CQ) was removed from front-line antimalarial chemotherapy in 1990s despite its initial promise disease eradication. Since then, resistance-conferring mutations have been identified transporters such as PfCRT, that allow for efflux CQ primary site action, parasite digestive vacuole. Chemosensitizing/chemoreversing compounds interfere with function these thereby sensitizing parasites once again. However, thus far...
Plasmodium falciparum is the etiological agent of malignant malaria and has been shown to exhibit features resembling programmed cell death. This triggered upon treatment with low micromolar doses chloroquine or other lysosomotrophic compounds associated leakage digestive vacuole contents. In order exploit this death pathway, we developed a high-content screening method select that can disrupt parasite vacuole, as measured by intravacuolar Ca(2+). assay uses ImageStream 100, an...
Abstract The spread of artemisinin-resistant parasites could lead to higher incidence patients with malaria complications. However, there are no current treatments that directly dislodge sequestered from the microvasculature. We show four common antiplasmodial drugs do not disperse rosettes (erythrocyte clusters formed by parasites) and therefore develop a cell-based high-throughput assay identify potential rosette-disrupting compounds. A pilot screen 2693 compounds identified Malaria Box...
Naturally acquired antibodies to proteins expressed on the Plasmodium falciparum parasitized red blood cell (pRBC) surface steer course of a malaria infection by reducing sequestration and stimulating phagocytosis pRBC. Here we have studied selection representing three different parasite gene families employing well-characterized with severe phenotype (FCR3S1.2). The presence naturally antibodies, impact rosetting rate, reactivity opsonization for in relation groups ABO system were assessed...
Plasmodium falciparum genome has 81% A+T content. This nucleotide bias leads to extreme codon usage and culminates in frequent insertion of asparagine homorepeats the proteome. Using recodonized GFP sequences, we show that codons decoded via G:U wobble pairing are suboptimal negatively associated protein translation efficiency. Despite this, one third all GU codons, suggesting P. not been driven maximize efficiency, but may have evolved as translational regulatory mechanism. Particularly,...
Plasmodium falciparum invasion into red blood cells (RBCs) is a complex process engaging proteins on the merozoite surface and those contained sequentially released from apical organelles (micronemes rhoptries). Fundamental to formation of moving junction (MJ), region close apposition RBC plasma membranes, through which draws itself before settling newly formed parasitophorous vacuole (PV). SURFIN4.2 was identified at parasitized RBCs (pRBCs) but also found apically associated with...
Rising prevalence of diabetes in sub-Saharan Africa, coupled with continued malaria transmission, has resulted more patients dealing both communicable and non-communicable diseases. We previously reported that travelers type 2 mellitus (T2DM) infected Plasmodium falciparum were three times likely to develop severe than non-diabetics. Here we explore the biological basis for this by testing blood from uninfected subjects 1 diabetes, ex vivo, their effects on parasite growth rosetting (binding...
Abstract Variable surface antigens of Plasmodium falciparum have been a major research focus since they facilitate parasite sequestration and give rise to deadly malaria complications. Coupled with its potential use as vaccine candidate, the recent suggestion that repetitive interspersed families polypeptides (RIFINs) mediate blood group A rosetting influence distribution has raised profile these adhesins. Nevertheless, detailed investigations into functions this highly diverse multigene...
Introduction: We frequently associate microbes with infection, rarely expounding on their usefulness and importance to healthy development. For humanity leverage these microbial “super powers”, learners from all backgrounds need appreciate utility consider how could help solve some of the most critical problems we face. However, are uninterested or intimidated by microbiology. The card game “No Guts No Glory” was created engage students piquing curiosity encouraging informal learning change...