Our major interest is the drugs (anthelmintics) used to treat and prevent infections with parasitic roundworms (nematodes) in humans and animals. We are also very interested in the mechanisms by which the parasites become resistant to these drugs. Most anthelmintics target the nematode nervous system, causing paralysis and death, so we study the components of the nervous system affected by anthelmintics, specifically nicotinic acetylcholine receptors and glutamate-gated chloride channels.
Our current projects include attempting to unravel the mechanisms of action of ivermectin and diethylcarbamizine against filarial parasites such as Brugia malayi, which is a causative agent of lymphatic filariasis, and Dirofilaria immitis, the dog heartworm. We are applying transcriptomic techniques to try and unravel the effects of drug treatment on the worms and, possibly, the host. Many parasitic nematodes are able to profoundly modulate the host immune system and we are actively testing the hypothesis that the efficacy of the anthelmintics is due, at least in part, to inhibition of this modulation.
Anthelmintic resistance is a major problem in veterinary medicine. It is rampart in livestock parasites, such as Haemonchus contortus, which have become to just about all the drugs available, and has recently been confirmed in heartworm, where only a single class of compound is available to prevent disease. We are seeking to develop and evaluate molecular markers and tests for resistance.
Parasitic nematodes are difficult to study, so we are examining the possibility that genes from parasites can be expressed in the free-living worm, Caenorhabditis elegans, using subunits of the nicotinic acetylcholine receptor as a model.