A5056610190- Malaria Research and Control
- Mosquito-borne diseases and control
- Atherosclerosis and Cardiovascular Diseases
- Single-cell and spatial transcriptomics
- Vector-borne infectious diseases
- Microbial infections and disease research
- Computational Drug Discovery Methods
- Aquaculture disease management and microbiota
- Trypanosoma species research and implications
- vaccines and immunoinformatics approaches
- Genetic Associations and Epidemiology
- Cardiovascular Function and Risk Factors
- Genomics and Phylogenetic Studies
- Cardiovascular Health and Risk Factors
- Cardiovascular Disease and Adiposity
- Adipokines, Inflammation, and Metabolic Diseases
- Heart Rate Variability and Autonomic Control
- Dengue and Mosquito Control Research
- HIV/AIDS drug development and treatment
- Healthcare Systems and Public Health
- ECG Monitoring and Analysis
- Health, Environment, Cognitive Aging
- Cancer-related molecular mechanisms research
- Pluripotent Stem Cells Research
- Invertebrate Immune Response Mechanisms
Utrecht University
2021-2025
University Medical Center Utrecht
2021-2025
Heidelberg University
2023-2024
University Hospital Heidelberg
2023-2024
London School of Hygiene & Tropical Medicine
2015-2023
Mayo Clinic in Arizona
2020-2022
University of London
2017-2021
University of St Andrews
2021
St Bartholomew's Hospital
2018
Antimicrobial resistance (AMR) poses a threat to public health. Clinical microbiology laboratories typically rely on culturing bacteria for antimicrobial-susceptibility testing (AST). As the implementation costs and technical barriers fall, whole-genome sequencing (WGS) has emerged as ‘one-stop’ test epidemiological predictive AST results. Few published comparisons exist myriad analytical pipelines used predicting AMR. To address this, we performed an inter-laboratory study providing sets of...
Tackling relapsing Plasmodium vivax and zoonotic knowlesi infections is critical to reducing malaria incidence mortality worldwide. Understanding the biology of these important related parasites was previously constrained by lack robust molecular genetic approaches. Here, we establish CRISPR-Cas9 genome editing in a culture-adapted P. strain define parameters for optimal homology-driven repair. We scalable protocol production repair templates PCR demonstrate flexibility system tagging...
Coronary artery disease (CAD) is the leading cause of death worldwide. Recent meta-analyses genome-wide association studies have identified over 175 loci associated with CAD. The majority these are in noncoding regions and predicted to regulate gene expression. Given that vascular smooth muscle cells (SMCs) play critical roles development progression CAD, we aimed identify subset CAD regulation transcription distinct SMC phenotypes.
A highly efficacious vaccine is needed for malaria control and eradication. Immunization with Plasmodium falciparum NF54 parasites under chemoprophylaxis (chemoprophylaxis sporozoite (CPS)-immunization) induces the most efficient long-lasting protection against a homologous parasite. However, parasite genetic diversity major hurdle heterologous strains. We conducted double-blind, randomized controlled trial in 39 healthy participants of NF54-CPS immunization by bites 45 NF54-infected (n = 24...
Malaria in humans is caused by six species of Plasmodium parasites, which the nuclear genome sequences for two ovale spp., P. curtisi and wallikeri, malariae have not yet been analyzed. Here we present an analysis these three describe gene family expansions therein. wallikeri are genetically distinct but morphologically indistinguishable sympatric ranges through tropics Africa, Asia Oceania. Both spp. show expansion surfin variant family, amplification interspersed repeat (pir) superfamily...
Abstract The incidence of Plasmodium vivax infection has declined markedly in Malaysia over the past decade despite evidence high-grade chloroquine resistance. Here we investigate genetic changes a P. population approaching elimination 51 isolates from Sabah, and compare these with data 104 Thailand Indonesia. Sabah displays extensive structure, mirroring that previously seen emergence artemisinin-resistant falciparum founder populations Cambodia. Fifty-four percent have identical genomes,...
Preterm birth is associated with both psychological and physical disabilities the leading cause of infant morbidity mortality worldwide. Infection known to be an important spontaneous preterm birth, recent research has implicated variation in “placental microbiome” risk birth. Consistent data from previous studies, abundances certain clinically relevant species differed between preterm- nonspontaneous or term-delivered placentas. These results support view that a proportion births have...
Background: Tuberculosis disease, caused by Mycobacterium tuberculosis, is a major public health problem. The emergence of M. tuberculosis strains resistant to existing treatments threatens derail control efforts. Resistance mainly conferred mutations in genes coding for drug-targets or -converting enzymes, but our knowledge these incomplete. Whole genome sequencing (WGS) an increasingly common approach rapidly characterize isolates and identify predicting antimicrobial resistance, thereby...
Russia has one of the highest rates cardiovascular disease in world. The International Project on Cardiovascular Disease (IPCDR) was set up to understand reasons for this. A substantial component this study Know Your Heart Study devoted characterising nature and causes by conducting large cross-sectional surveys two Russian cities Novosibirsk Arkhangelsk. population 4542 men women aged 35-69 years recruited from general population. Fieldwork took place between 2015-18. There were components:...
Despite the high burden of Plasmodium vivax malaria in South Asian countries, genetic diversity circulating parasite populations is not well described. Determinants antimalarial drug susceptibility for P. region have been characterised. Our genomic analysis global (n = 558) establishes isolates 92) as a distinct subpopulation, which shares ancestry with some East African and parasites. Signals positive selection are linked to resistance-associated loci including pvkelch10, pvmrp1, pvdhfr...
ObjectiveTo validate a novel artificial-intelligence electrocardiogram algorithm (AI-ECG) to detect left ventricular systolic dysfunction (LVSD) in an external population.BackgroundLVSD, even when asymptomatic, confers increased morbidity and mortality. We recently derived AI-ECG LVSD using ECGs based on large sample of patients treated at the Mayo Clinic.MethodsWe performed validation study with subjects from Know Your Heart Study, cross-sectional adults aged 35–69 years residing two cities...
Brazil is a unique and understudied setting for malaria, with complex foci of transmission associated human environmental conditions. An understanding the population genomic diversity
Abstract Background After myocardial infarction, the lost myocardium is replaced by fibrotic tissue, eventually progressively leading to dysfunction. Direct reprogramming of fibroblasts into cardiomyocytes via forced overexpression cardiac transcription factors Gata4, Mef2c, and Tbx5 (GMT) offers a promising strategy for repair. The limited efficiency this approach, however, remains significant challenge. Methods We screened seven capable improving direct both mice human evaluating small...
Epigenetic age estimators (clocks) are predictive of human mortality risk. However, it is not yet known whether the epigenetic atherosclerotic plaques for risk cardiovascular events.
Abstract Artificial intelligence (AI)-based approaches can now use electrocardiograms (ECGs) to provide expert-level performance in detecting heart abnormalities and diagnosing disease. Additionally, patient age predicted from ECGs by AI models has shown great potential as a biomarker for cardiovascular age, where recent work found its deviation chronological (“delta age”) be associated with mortality co-morbidities. However, despite being crucial understanding underlying individual risk,...
Women presenting with coronary artery disease more often present fibrous atherosclerotic plaques, which are currently understudied. Phenotypically modulated smooth muscle cells (SMCs) contribute to atherosclerosis in women. How these phenotypically SMCs shape female versus male plaques is unknown.
Malawi experienced prolonged use of sulfadoxine/pyrimethamine (SP) as the front-line anti-malarial drug, with early replacement chloroquine and delayed introduction artemisinin-based combination therapy. Extended SP, its continued application in pregnancy is impacting genomic variation Plasmodium falciparum population. Whole genome sequence data P. isolates covering 2 years transmission within Malawi, alongside global datasets, were used. More than 745,000 SNPs identified, differences allele...
Background Although Plasmodium vivax contributes to almost half of all malaria cases outside Africa, it has been relatively neglected compared the more deadly P. falciparum. It is known that populations possess high genetic diversity, differing geographically potentially due different vector species, host genetics and environmental factors. Results We analysed high-quality genomic data for 46 isolates spanning 10 countries across 4 continents. Using population methods we identified hotspots...
Abstract Malaria infection during pregnancy, caused by the sequestering of Plasmodium falciparum parasites in placenta, leads to high infant mortality and maternal morbidity. The parasite-placenta adherence mechanism is mediated VAR2CSA protein, a target for natural occurring immunity. Currently, vaccine development based on its ID1-DBL2Xb domain however little known about global genetic diversity encoding var2csa gene, which could influence efficacy. In comprehensive analysis gene >2,000...
Although Plasmodium vivax parasites are the predominant cause of malaria outside sub-Saharan Africa, they not always prioritised by elimination programmes. P. is resilient and poses challenges through its ability to re-emerge from dormancy in human liver. With observed growing drug-resistance increasing reports life-threatening infections, new tools inform efforts needed. In order halt transmission, we need better understand dynamics movement parasites, reservoirs infection design targeted...