Neglected Diseases (NTDs) caused by parasitic worms (helminths) impose a debilitating health and economic burden throughout much of the world. These global diseases of poverty infect over 1.5 billion humans and exert their damage through a wide range of species-specific clinical manifestations. Parasitic diseases are also a major challenge to animal and plant health. The central ambition of our laboratory is to combine molecular biology, genetics, and computational approaches to make discoveries that improve our understanding of parasite biology and our ability to treat parasitic infections. This includes the identification of new targets for drug discovery, the elucidation of mechanisms of drug resistance, and the development of new tools for parasite manipulation and phenotypic screening. Our work involves the direct study of human and animal parasites, including the mosquito-borne nematodes Brugia malayi and Dirofilaria immitis, and the snail-transmitted blood fluke Schistosoma mansoni. To complement these efforts, we leverage the power of the model nematode Caenorhabditis elegans. We strive to place our work in the context of a growing appreciation for parasite genetic diversity. Summaries of current research projects are outlined on this page.
Current and Past Funding Sources
Drug Target Discovery at the Host-Parasite Interface:Driven by the need for new antiparasitics, we apply genomic, reverse genetic, and pharmacological approaches to identify and characterize new drug targets in filarial nematode parasites. We are focused on cell-surface proteins that mediate critical aspects of the host-parasite interaction. These include parasite receptors that control (1) secretory processes involved in host communication, (2) invasion and migration through host tissues, and (3) neuromuscular and feeding behaviors. We heve developed in vivo and in vitro parasite assays to associate specific receptors with phenotypes that can potentially be targetted to prevent or disrupt disease. We are working to move these candidate drug targets into both single-cell and model nematode heterolougous screening platforms.
Anthelmintic Resistance and Action:Motivated by the threat of anthelmintic resistance in parasite populations, we work to help resolve genes and genetic variation that modulate drug sensitivity in clade III filarial and soil-transmitted parasites. This work involves the localization of drug-responsive targets within parasite cells and tissues, the functional expression of parasite genes in model nematode systems, and introducing and assaying the effects of candidate resistance mutations on drug response.
Improving Helminths Resources and Tools:To complement our hypothesis-driven work, we are engaged in a number of projects to improve the state of helminth genomic data and the tools available to experimentally manipulate helminth systems. This includes ongoing work to (1) capture full-length RNA transcripts and reduce molecular cloning efforts, (2) deliver spatial maps of RNA expression in nematodes, and (3) adapt and further develop genetic manipulation strategies in parasites and their vectors. These efforts provide us more powerful data and tools to make progress on our core aims.