Juliet Fuhrman

Our laboratory studies the basic biology of parasitic roundworms in the hope of devising novel strategies for controlling infection and preventing disease. We focus in particular on filarial parasites, which are responsible for causing human elephantiasis and river blindness as well as dog heartworm. Filarial parasites currently infect more than 100 million people worldwide, most of whom live in developing nations. We have a longstanding interest in chitin metabolism as a therapeutic target for parasitic nematodes. Chitin is a structural polysaccharide used by insects, fungi, and crustaceans, but chitin is not synthesized by vertebrates. Thus, the chitin synthase enzyme should be a suitable target for parasite-specific therapeutics. Our laboratory has characterized the genes and enzymes for chitin synthase as well as chitinase from the filarial parasites Brugia malayi, which causes human elephantiasis, and Dirofilaria immitis, which causes dog heartworm. Through a variety of molecular and biochemical methods, we have described the activities of these enzymes and their importance in the nematode life cycle. Current research focuses on the regulation of chitin synthesis during eggshell formation, and the use of chitin for somatic structures in larvae and adults. The extensive information available for the free-living nematode, C. elegans, has allowed us to use this model system to dissect developmental processes that are common to all roundworms. Other work in our laboratory has examined the molecular basis of pathogenesis in lymphatic filariasis. We have demonstrated that certain stages produce nitric oxide, a potent mediator of vessel dilation and inflammation, suggesting that the parasite modulates the host tissue environment in specific ways that lead to disease.