A5004877981- Mosquito-borne diseases and control
- Malaria Research and Control
- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Fungal Infections and Studies
- Genomics and Phylogenetic Studies
- Hemoglobinopathies and Related Disorders
- Immune Response and Inflammation
- Parasite Biology and Host Interactions
- Plant-Microbe Interactions and Immunity
- Antifungal resistance and susceptibility
- Zebrafish Biomedical Research Applications
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Evolution and Genetic Dynamics
- Infectious Diseases and Tuberculosis
- Hepatitis C virus research
- Immune responses and vaccinations
- Phytoplasmas and Hemiptera pathogens
- HIV Research and Treatment
- Galectins and Cancer Biology
- Phagocytosis and Immune Regulation
- interferon and immune responses
- Extracellular vesicles in disease
- Viral Infections and Vectors
Pfizer (United States)
2025
Duke University
2015-2022
Duke University Hospital
2015-2018
Duke Medical Center
2015-2018
Loyola University Chicago
2012-2018
The human pathogen Mycobacterium tuberculosis typically causes lung disease but can also disseminate to other tissues. We identified a M. (Mtb) outbreak presenting with unusually high rates of extrapulmonary dissemination and bone disease. found that the causal strain carried an ancestral full-length version type VII-secreted effector EsxM rather than truncated present in modern Mtb lineages. variant exacerbated through enhancement macrophage motility, increased egress macrophages from...
Abstract Host genetic factors can confer resistance against malaria 1 , raising the question of whether this has led to evolutionary adaptation parasite populations. Here we searched for association between candidate host and variants in 3,346 Gambian Kenyan children with severe caused by Plasmodium falciparum . We identified a strong sickle haemoglobin (HbS) three regions genome, which is not explained population structure or other covariates, replicated additional samples. The...
Visualization of infection and the associated host response has been challenging in adult vertebrates. Due to their transparency, zebrafish larvae have used directly observe vivo, but as not yet developed a functional adaptive immune system. Thus, study many aspects vertebrate requires dissection organs or ex vivo isolation cells. Cells involved immunity mature later thus difficult access optically intact animals. Recently, CLARITY PACT methodologies enabled clearing direct visualization...
The work described here further elucidates how microorganisms sense and adapt to changes in their environment establish infections the human host. Specifically, we uncover a novel mechanism by which an opportunistic fungal pathogen, Cryptococcus neoformans , responds increases extracellular pH order survive thrive within relatively alkaline of lung. This mechanism, is intimately linked with membrane sterol homeostasis, independent previously well-studied response Rim pathway. Furthermore,...
Microbial pathogens generate extracellular vesicles (EVs) for intercellular communication and quorum sensing. EVs also induce inflammatory pathways within host innate immune cells. We previously demonstrated that secreted by
Abstract Novel interventions that leverage the heterogeneity of parasite transmission are needed to achieve malaria elimination. To better understand spatial and temporal dynamics transmission, we applied amplicon next-generation sequencing two polymorphic gene regions ( csp ama1 ) a cohort identified via reactive case detection in high-transmission setting western Kenya. From April 2013 July 2014, enrolled 442 symptomatic children with malaria, matched controls, all household members both...
Abstract Background In many genomes, a clear preference in the usage of particular codons exists. The mechanisms that induce codon biases remain an open question; studies have attributed to translational selection, mutational bias and drift. Furthermore, correlations between within host genomes their viral pathogens been observed for myriad host-virus systems. As such, numerous investigated effort better understand how species evolve. Numerous metrics developed identify usage. addition, few...
The mechanisms by which micro-organisms sense and internalize extracellular pH signals are not completely understood. One example of a known external pH-sensing process is the fungal-specific Rim/Pal signal transduction pathway. Fungi, such as opportunistic pathogen Cryptococcus neoformans, use Rim signaling to respond changes in environmental pH. Mutations this pathway result strains that attenuated for survival at alkaline pH, often within host. Here, we used an insertional mutagenesis...
Limited data are available regarding the molecular epidemiology of Mycobacterium tuberculosis (Mtb) strains circulating in Guatemala. Beijing-lineage Mtb have gained prevalence worldwide and associated with increased virulence drug resistance, but there been only a few cases reported Central America. Here we report first whole genome sequencing American Mtb. We find that multiple strains, derived from independent founding events, currently Guatemala, overall still represent relatively small...
ABSTRACT The well-established safety profile of the tuberculosis vaccine strain, Mycobacterium bovis bacille Calmette-Guérin (BCG), makes it an attractive vehicle for heterologous expression antigens from clinically relevant pathogens. However, successful generation recombinant BCG strains possessing consistent insert has encountered challenges in stability. Here, we describe a method development large accession lots which stably express lentiviral antigens, human immunodeficiency virus...
Sickle-trait hemoglobin protects against severe Plasmodium falciparum malaria. Severe malaria is governed in part by the expression of Erythrocyte Membrane Protein 1 (PfEMP1) that are encoded var genes, specifically those variants bind Endothelial C Receptor (EPCR). In this study, we investigate effect sickle-trait on parasite gene and function vitro field-collected parasites. We mapped reads generated from RNA sequencing cultures normal sickle-cell trait blood throughout asexual lifecycle....
Sickle-trait hemoglobin (HbAS) confers nearly complete protection from severe, life-threatening falciparum malaria in African children. Despite this clear protection, the molecular mechanisms by which HbAS these protective phenotypes remain incompletely understood. As a forward genetic screen for aberrant parasite transcriptional responses associated with neutralization red blood cells (RBCs), we performed comparative transcriptomic analyses of Plasmodium normal (HbAA) and erythrocytes...
Viruses rely upon their hosts for biosynthesis of viral RNA, DNA and protein. This dependency frequently engenders strong selection virus genome compatibility with potential hosts, appropriate gene regulation expression necessary a successful infection. While bioinformatic studies have shown correlations between codon usage in host genomes, the selective factors by which this evolves remain matter conjecture. Engineered to include codons lesser and/or tRNA abundance within host, three...
Whole-genome sequencing has resulted in new insights into the phylogeography of Mycobacterium tuberculosis However, only limited genomic data are available from M. strains Guatemala. Here we report 16 complete genomes clinical belonging to Euro-American lineage 4, most common found Guatemala and Central America.
ABSTRACT Novel interventions that leverage the heterogeneity of parasite transmission are needed to push malaria further towards elimination. To better understand spatial and temporal dynamics transmission, we applied amplicon NGS two polymorphic gene regions ( csp ama1 ) a cohort identified via reactive case detection in high-transmission setting western Kenya. From 4/2013–6/2014, enrolled 442 symptomatic children with malaria, matched controls, all household members both groups. We...
Abstract The ability for cells to maintain homeostasis in the presence of extracellular stress is essential their survival. Stress adaptations are especially important microbial pathogens respond rapidly changing conditions, such as those encountered during transition from environment infected host. Many fungal have acquired quickly adapt changes pH promote survival various micro-environments a host infection. For example, fungal-specific Rim/Pal alkaline response pathway has been well...
Abstract Sickle-trait hemoglobin (HbAS) confers near-complete protection from severe, life-threatening falciparum malaria in African children. Despite this clear protection, the molecular mechanisms by which HbAS these protective phenotypes remain incompletely understood. As a forward genetic screen for aberrant parasite transcriptional responses associated with neutralization red blood cells (RBCs), we performed comparative transcriptomic analyses of Plasmodium normal (HbAA) and...