A5036679332- Malaria Research and Control
- Mosquito-borne diseases and control
- Genetic diversity and population structure
- Evolution and Genetic Dynamics
- HIV Research and Treatment
- Hemoglobinopathies and Related Disorders
- Diabetes and associated disorders
- Trypanosoma species research and implications
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- Vibrio bacteria research studies
- Computational Drug Discovery Methods
- Travel-related health issues
- Hepatitis C virus research
- interferon and immune responses
- Parasite Biology and Host Interactions
- Celiac Disease Research and Management
- Drug Transport and Resistance Mechanisms
- Lymphoma Diagnosis and Treatment
- Digestive system and related health
- vaccines and immunoinformatics approaches
- Ubiquitin and proteasome pathways
- Vector-borne infectious diseases
- Parasites and Host Interactions
- Genetics, Bioinformatics, and Biomedical Research
University of Massachusetts Chan Medical School
2015-2024
Brown University
2019-2023
John Brown University
2019-2020
In Uganda, artemether-lumefantrine is recommended for malaria treatment and sulfadoxine-pyrimethamine chemoprevention during pregnancy, but drug resistance may limit efficacies. Genetic polymorphisms associated with sensitivities to key drugs were characterized in samples collected from 16 sites across Uganda 2018 2019 by ligase detection reaction fluorescent microsphere, molecular inversion probe, dideoxy sequencing, quantitative polymerase chain assays. Considering transporter...
In Africa, most rapid diagnostic tests (RDTs) for falciparum malaria recognize histidine-rich protein 2 antigen. Plasmodium parasites lacking (pfhrp2) and 3 (pfhrp3) genes escape detection by these RDTs, but it is not known whether deletions confer sufficient selective advantage to drive population expansion. By studying blood samples from a cohort of 12,572 participants enroled in prospective, cross-sectional survey along Ethiopia's borders with Eritrea, Sudan South using PCR, an...
A better understanding of the drivers spread malaria parasites and drug resistance across space time is needed. These can be elucidated using genetic tools. Here, a novel molecular inversion probe (MIP) panel targeting all major drug-resistance mutations set microsatellites was used to genotype Plasmodium falciparum infections 552 children from 2013-2014 Demographic Health Survey conducted in Democratic Republic Congo (DRC). Microsatellite-based analysis population structure suggests that...
Abstract The Democratic Republic of the Congo (DRC) harbors 11% global malaria cases, yet little is known about spatial and genetic structure parasite population in that country. We sequence 2537 Plasmodium falciparum infections, including a nationally representative sample from DRC samples surrounding countries, using molecular inversion probes - high-throughput genotyping tool. identify an east-west divide haplotypes to confer resistance chloroquine sulfadoxine-pyrimethamine. Furthermore,...
Intron-containing RNA expressed from the HIV-1 provirus activates type 1 interferon in primary human blood cells, including CD4 + T macrophages, and dendritic cells. To identify innate immune receptor required for detection of intron-containing provirus, a loss-of-function screen was performed with short hairpin RNA-expressing lentivectors targeting twenty-one candidate genes monocyte-derived Among tested, only knockdown XPO1 (CRM1), IFIH1 (MDA5), or MAVS prevented activation...
Abstract Background Targeted next-generation sequencing offers the potential for consistent, deep coverage of information-rich genomic regions to characterize polyclonal Plasmodium falciparum infections. However, methods identify and sequence these are currently limited. Methods A bioinformatic pipeline multiplex were developed simultaneously 100 targets applied dried blood spot (DBS) controls field isolates from Mozambique. For comparison, whole-genome data generated same controls. Results...
High-throughput Plasmodium genomic data is increasingly useful in assessing prevalence of clinically important mutations and malaria transmission patterns. Understanding parasite diversity for identification specific human or populations that can be targeted by control programmes, to monitor the spread associated with drug resistance. An up-to-date understanding regional population dynamics also critical impact efforts. However, this largely absent from high-burden nations Africa, date, no...
Treatment and control of malaria depends on artemisinin-based combination therapies (ACTs) is challenged by drug resistance, but thus far resistance to artemisinins partner drugs has primarily occurred in southeast Asia. The aim this study was characterise antimalarial susceptibility Plasmodium falciparum isolates from Tororo Busia districts Uganda. In prospective longitudinal study, P were collected patients aged 6 months or older presenting at the District Hospital (Tororo district, a site...
Tanzania's Zanzibar archipelago has made significant gains in malaria control over the last decade and is a target for elimination. Despite consistent implementation of effective tools since 2002, elimination not been achieved. Importation parasites from outside thought to be an important cause malaria's persistence, but this paradigm studied using modern genetic tools. Whole-genome sequencing (WGS) was used investigate impact importation, employing population analyses Plasmodium falciparum...
The HER2 + subtype of human breast cancer is associated with the malignant transformation luminal ductal cells mammary epithelium. sequence analysis tumor DNA identifies loss function mutations and deletions MAP2 K4 K7 genes that encode direct activators JUN NH 2 -terminal kinase (JNK). We report in vitro studies epithelial CRISPR-induced MAPK MAP2K components JNK pathway caused no change growth 2D culture, but these promoted cell proliferation 3D culture. Analysis gene expression signatures...
Abstract Malaria transmission depends on the presence of Plasmodium gametocytes that are only parasite life stage can infect mosquitoes. Gametocyte production varies between infections and over course infections. Infection duration is highly important for gametocyte but poorly quantified. Between 2017 2019 an all-age cohort individuals from Tororo, eastern Uganda was followed by continuous passive routine assessments. We longitudinally monitored 104 incident 98 who were sampled once every 28...
Abstract Background Understanding temporal and spatial dynamics of malaria transmission will help to inform effective interventions strategies in regions approaching elimination. Parasite genomics are increasingly used monitor epidemiologic trends, including assessing residual across seasons importation into these regions. Methods In a low seasonal setting southern Zambia, total 441 Plasmodium falciparum samples collected from 8 neighbouring health centres between 2012 2018 were genotyped...
Intragenic microRNAs (miRNAs), located mostly in the introns of protein-coding genes, are often co-expressed with their host mRNAs. However, functional interaction development is largely unknown. Here we show that Drosophila, miR-92a and miR-92b embedded intron 3'UTR jigr1, respectively, some jigr1 isoforms. highly expressed neuroblasts larval brain where Jigr1 expression low. Genetic deletion both demonstrates an essential cell-autonomous role for these miRNAs maintaining neuroblast...
A key drawback to monitoring the emergence and spread of antimalarial drug resistance in sub-Saharan Africa is early detection containment. Next-generation sequencing methods offer resolution, sensitivity, scale required fill this gap by surveilling for molecular markers resistance. We performed targeted using inversion probes interrogate five Plasmodium falciparum genes ( pfcrt , pfmdr1 pfdhps pfdhfr pfk13 ) implicated chloroquine, sulfadoxine-pyrimethamine (SP), artemisinin two sites Ghana.
Abstract Background Drug resistant malaria is a growing concern in the Democratic Republic of Congo (DRC), where previous studies indicate that parasites to sulfadoxine/pyrimethamine or chloroquine are spatially clustered. This study explores longitudinal changes spatial patterns understand how may be spreading within DRC, using samples from nation-wide population-representative surveys. Methods We selected 552 children with PCR-detectable Plasmodium falciparum infection and identified known...
Improved viral enrichment methods conclusively demonstrate EBV type 1 to be more prevalent in eBL patients than geographically matched healthy controls, which previously underrepresented the prevalence of 2. Genome-wide association analysis between cases and controls identifies six eBL-associated nonsynonymous variants EBNA1, EBNA2, BcLF1, BARF1 genes. Analysis population structure reveals that 2 exists as two genomic subgroups was commonly found female male patients.
Adults are frequently infected with malaria and may serve as a reservoir for further transmission, yet we know relatively little about risk factors adult infections. In this study, assessed among adults using samples from the nationally representative, cross-sectional 2013-2014 Demographic Health Survey (DHS) conducted in Democratic Republic of Congo (DRC). We explored differences by urbanicity. Plasmodium falciparum infection was determined PCR. Covariates were drawn DHS to model...
Type 1 diabetes (T1D) involves the interaction of multiple gene variants, environmental factors, and immunoregulatory dysfunction. Major T1D genetic risk loci encode HLA-DR -DQ. Genetic heterogeneity linkage disequilibrium in highly polymorphic HLA region confound attempts to identify additional susceptibility loci. To minimize heterogeneity, patients (N = 365) control subjects 668) homozygous for HLA-DR3 high-risk haplotype were selected from large studies examined new using molecular...
Drug resistance necessitates the development of new antimalarial drugs. It is important to assess activities compounds under against parasites now causing disease in Africa, where most malaria cases occur, and determine if mutations these may limit efficacies agents.
In malaria, individuals are often infected with different parasite strains. The complexity of infection (COI) is defined as the number genetically distinct strains in an individual. Changes mean COI a population have been shown to be informative changes transmission intensity probabilistic likelihood and Bayesian models now developed estimate COI. However, rapid, direct measures based on heterozygosity or FwS do not properly represent this work, we present two new methods that use easily...
Artemether-lumefantrine (AL) is a first-line agent for uncomplicated malaria caused by Plasmodium falciparum. The WHO recommends periodic therapeutic efficacy studies of antimalarial drugs the detection parasite drug resistance and to inform national treatment policies. We conducted study AL in high transmission region northern Zambia from December 2014 July 2015. One hundred children ages 6 59 months presenting rural health clinic with falciparum were admitted (standard 6-dose regimen)...
Plasmodium falciparum resistance to artemisinin-based combination therapies (ACTs) is a threat malaria elimination. ACT-resistance in Asia raises concerns for emergence of Africa. While most data show high efficacy ACT regimens Africa, there have been reports describing declining efficacy, as measured by both clinical failure and prolonged parasite clearance times. Three hundred children aged 2-10 years with uncomplicated P. infection were enrolled Kenya Tanzania after receiving treatment...
Abstract Plasmodium ovale curtisi ( Poc) and wallikeri Pow ) are relapsing malaria parasites endemic to Africa Asia that were previously thought represent a single species. Amid increasing detection of in sub-Saharan Africa, we performed population genomic study both species across the continent. We conducted whole-genome sequencing 25 isolates from Central East analyzed them alongside 20 published African genomes. Isolates predominantly monoclonal (43/45), with their genetic similarity...
Plasmodium vivax transmission occurs throughout the tropics and is an emerging threat in areas of falciparum decline, causing relapse infections that complicate treatment control. Targeted sequencing for P. has been widely deployed to detect population structure geographic spread antimalarial diagnostic resistance. However, there are fewer such tools vivax. Leveraging global variation data, we designed four molecular inversion probe (MIP) genotyping panels targeting geographically...