Identification of Nematode Nuclear Hormone Receptors

Analogs of steroid hormones have been a fruitful source of a variety of drug therapies as theyeasily cross cell membranes and modulate transcriptional activity via their nuclear hormone receptors(NHR). The identification of nematode steroid hormones, and subsequently their analogs, could be afruitful source of anthelminthic drug therapies; while the identification of nematode NHR-regulated genescould be a source of vaccine candidates. The insect steroid molting hormone, ecdysone, and its receptor(EcR) is of particular interest because of its essential role in development, its presence and biologicaleffects in nematodes, and its absence from parasitic nematode hosts. Study of the nematodeEcR-regulated genes will stimulate the development of anti-molting drugs and vaccine candidates. UsingEcR-specific reagents and the highly conserved nature of the NHR superfamily, the existence of EcRhomologs will be determined for Dirofilaria immitis, dog heartworm, and the free living nematode,Caenorhabditis elegans. D. immitis offers a large market for drug therapies and vaccines, while thegenetic and molecular foundation of C. elegans allows for greater experimentation. The expressionpattern, function, and drug target potential will be studied for any nematode EcR and any molt-regulatingNHR identified.