A5042360149- Parasite Biology and Host Interactions
- Parasitic Diseases Research and Treatment
- Parasites and Host Interactions
- Insect symbiosis and bacterial influences
- Helminth infection and control
- Evolution and Genetic Dynamics
- Neurobiology and Insect Physiology Research
- Phytochemistry and Bioactivity Studies
- Computational Drug Discovery Methods
- Chemical synthesis and alkaloids
- Identification and Quantification in Food
- Fungal Biology and Applications
- Protein Structure and Dynamics
- Planarian Biology and Electrostimulation
- Plant Pathogenic Bacteria Studies
- Piperaceae Chemical and Biological Studies
- Machine Learning in Bioinformatics
- bioluminescence and chemiluminescence research
- Nematode management and characterization studies
- Entomopathogenic Microorganisms in Pest Control
- Insect Utilization and Effects
- Extracellular vesicles in disease
- Aquaculture disease management and microbiota
- Chromosomal and Genetic Variations
- Insect and Arachnid Ecology and Behavior
University of Wisconsin–Eau Claire
2023-2025
University of Wisconsin–Madison
2018-2023
Merck Serono (Switzerland)
2019
Iowa State University
2012-2018
Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans animals, decimate crop production are a major impediment to socioeconomic development. Here we report broad comparative study 81 genomes parasitic non-parasitic worms. We have identified gene family births hundreds expanded families at key nodes in the phylogeny that relevant parasitism. Examples include modulate host immune responses, enable parasite migration though tissues or...
Lymphatic filariasis (LF) afflicts over 60 million people worldwide and leads to severe pathological outcomes in chronic cases. The nematode parasites (Nematoda: Filarioidea) that cause LF require both arthropod (mosquito) intermediate hosts mammalian definitive for their propagation. invasion migration of filarial worms through host tissues are complex critical survival, yet little is known about the receptors signaling pathways mediate directed these medically important species. In order...
Abstract Lymphatic filariasis (LF) is a disease caused by parasitic filarial nematodes that endemic in 49 countries of the world and affects or threatens over 890 million people. Strategies to control LF rely heavily on mass administration anthelmintic drugs including ivermectin (IVM), macrocyclic lactone drug considered an Essential Medicine WHO. However, despite its widespread use therapeutic mode action IVM against not clear. We have previously reported secrete extracellular vesicles...
Lymphatic filariasis (LF) is a chronic debilitating neglected tropical disease (NTD) caused by mosquito-transmitted nematodes that afflicts over 60 million people. Control of LF relies on routine mass drug administration with antiparasitics clear circulating larval parasites but are ineffective against adults. The development effective adulticides hampered poor understanding the processes and tissues driving parasite survival in host. adult filariae head region contains essential control...
Abstract Vector-borne, filarial nematode diseases cause significant disease burdens in humans and domestic animals worldwide. Although there is strong direct evidence of parasite-driven immunomodulation mammalian host responses, less parasite the vector host. We have previously reported that all life stages Brugia malayi , a causative agent Lymphatic filariasis, secrete extracellular vesicles (EVs). Here we investigate immunomodulatory effects microfilariae-derived EVs on Aedes aegypti....
Image-based phenotypic screening is a fundamental technique used to better understand the basic biology of helminths and advance discovery new anthelmintics. Miniaturization platforms automated microscopy have led surge in imaging data necessitated software organize analyze these data. Traditionally, analyses are performed remotely on high-performance computers, often requiring an understanding command-line interface (CLI) ability write scripts control or job scheduler. Requiring access...
Advances in high-throughput and high-content imaging technologies require concomitant development of analytical software capable handling large datasets generating relevant phenotypic measurements. Several tools have been developed to analyze drug response phenotypes parasitic free-living worms, but these are siloed often limited specific instrumentation, worm species, single phenotypes. No unified tool exists diverse data worms provide a platform for future extensibility. We wrmXpress,...
Macrocyclic lactones are front-line therapies for parasitic roundworm infections; however, there no comprehensive studies on the activity of this drug class against flatworms. Ivermectin is well known to be inactive However, structure-activity relationship macrocyclic may vary across phyla, and it entirely possible other members do in fact show antiparasitic For example, several reports hinting at anti-schistosomal doramectin moxidectin. To explore further, we developed an automated imaging...
Abstract Development of direct acting macrofilaricides for the treatment human filariases is hampered by limitations in screening throughput imposed parasite life cycle. In vitro adult screens typically assess single phenotypes without prior enrichment chemicals with antifilarial potential. We developed a multivariate screen that identified dozens compounds submicromolar macrofilaricidal activity, achieving hit rate >50% leveraging abundantly accessible microfilariae. Adult assays were...
G protein-coupled receptors (GPCRs) represent the largest known superfamily of membrane proteins extending throughout Metazoa. There exists ample motivation to elucidate functional properties GPCRs given their role in signal transduction and prominence as drug targets. In many target organisms, these efforts are hampered by unreliable nature heterologous receptor expression platforms. We validate describe an alternative loss-of-function approach for ascertaining ligand protein coupling...
The aquatic pulmonate snail Biomphalaria glabrata is a significant vector and laboratory host for the parasitic flatworm Schistosoma mansoni, an etiological agent neglected tropical disease schistosomiasis. Much known regarding host-parasite interactions of these two organisms, B. embryonic (Bge) cell line has been invaluable resource in studies. BB02 genome sequence was recently released, but nothing variation between this reference Bge genome, which likely accumulated substantial genetic...
Infection with Schistosoma parasitic flatworms ( haematobium, mansoni and japonicum ) causes the neglected tropical disease schistosomiasis. There is a need to identify new chemotherapies treat these parasites, G-protein coupled receptors (GPCRs) are logical druggable targets explore given they control key aspects of schistosome biology such as neuromuscular function reproduction. Updated chromosome level genome assemblies for each three major species have recently been released. However,...
Neglected diseases caused by helminth infections impose a massive hindrance to progress in the developing world. While basic research on parasitic flatworms (platyhelminths) continues expand, researchers have yet broadly adopt free-living model complement study of these important parasites. We report high-coverage sequencing (RNA-Seq) and assembly transcriptome planarian Girardia tigrina across set dynamic conditions. The was annotated extensive orthology analysis used seed pipeline for...
Filarial parasitic nematodes (Filarioidea) cause substantial disease burden to humans and animals around the world. Recently there has been a coordinated global effort generate, annotate, curate genomic data from nematode species of medical veterinary importance. This resulted in two chromosome-level assemblies (Brugia malayi Onchocerca volvulus) 11 additional draft genomes Filarioidea. These reference facilitate comparative genomics explore basic helminth biology prioritize new drug vaccine...
Abstract Advances in high-throughput and high-content imaging technologies require concomitant development of analytical software capable handling large datasets generating relevant phenotypic measurements. Several tools have been developed to analyze drug response phenotypes parasitic free-living worms, but these are siloed often limited specific instrumentation, worm species, single phenotypes. No effort has made unify for analyzing data worms provide a platform future extensibility. We...
Abstract Development of direct acting macrofilaricides for the treatment human filariases is hampered by limitations in screening throughput imposed parasite life cycle. Efforts to circumvent arduous adult filariae include drug repurposing and high-throughput screens that target commensal bacteria. In vitro typically assess single phenotypes without prior enrichment chemicals with antifilarial potential. We developed a multivariate screen identified dozens compounds submicromolar...
The diversification of anthelmintic targets and mechanisms action will help ensure the sustainable control nematode infections in response to growing threat drug resistance. G protein-coupled receptors (GPCRs) are established human medicine but remain unexploited as substrates despite their important roles neuromuscular physiological processes.
Sensory pathways first elucidated in Caenorhabditis elegans are conserved across free-living and parasitic nematodes, even though each species responds to a diverse array of compounds. Most nematode sensory assays performed by tallying observations worm behavior on two-dimensional planes using agarose plates. These have been successful the study volatile sensation but poorly suited for investigation water-soluble gustation or nematodes without stage. In contrast, gustatory tend be tedious,...
Abstract Sensory pathways first elucidated in Caenorhabditis elegans are conserved across free-living and parasitic nematodes, even though each species responds to a diverse array of compounds. Most nematode sensory assays performed by tallying observations worm behavior on two-dimensional planes using agarose plates. These have been successful the study volatile sensation but poorly suited for investigation water-soluble gustation or nematodes without stage. In contrast, gustatory tend be...
Abstract The following protocol is for performing bivariate (motility and viability) phenotypic drug screens against Brugia spp. microfilariae (mf). It has been heavily optimized utilization with an ImageXpress high-content imager, but only small adaptations will be necessary usage similar imaging platforms.Mf are used immediately after receipt/extraction, the experiment should not run longer than 48 hours, which mf health rapidly deteriorates. We have had success recording motility at 12...
ABSTRACT Lymphatic filariasis (LF) is a chronic debilitating neglected tropical disease (NTD) caused by mosquito-transmitted nematodes that afflicts over 60 million people. Control of LF relies on routine mass drug administration with antiparasitics clear circulating larval parasites but are ineffective against adults. The development effective adulticides hampered poor understanding the processes and tissues driving parasite survival in host. adult filariae head region contains essential...