Description of Research Expertise

Research Interests
- Molecular control of infective larval development in parasitic nematodes.
- Sensory and neuronal regulation of the infective process in parasitic nematodes.
- Molecular signaling between parasites and their hosts.
- Seasonality of filarial transmission and anti-filarial chemotherapy.

Key words: Strongyloides, Caenorhabditis, Dirofilaria, transcription factor, dauer, G protein, TGF beta, parasite, nematode.

Description of Research
The Lok lab's primary interest is the endogenous mechanism governing developmental arrest and lifespan in parasitic nematodes. In the free-living nematode Caenorhabditis elegans, output from an insulin/IGF-like signal transduction pathway is critical to both these factors. We are currently using the intestinal parasite Strongyloides stercoralis to test the hypothesis that insulin signaling also regulates arrest and reactivation of infective, autoinfective and hypobiotic third-stage larvae, as well as lifespan in these chronic latent stages of parasitic nematodes. In beginning to test this hypothesis we have determined that genes encoding key elements of the C. elegans insulin/IGF pathway are conserved in S. stercoralis. We are now using C. elegans as a genetic surrogate to assess function of Strongyloides ilrk-1 and fktf-1, orthologs of the insulin receptor and forkhead transcription factor, respectively in the C. elegans insulin pathway. Specifically we are asking whether these genes can complement loss-of-function mutations in their orthologs when expressed in C. elegans as heterologous transgenes. In addition to our work with insulin-like signaling, we have also determined that elements of two other signal transduction pathways that regulate dauer development in C. elegans, a G protein-mediated odorant receptor pathway and a TGF-β-like signal pathway, are also conserved in S. stercoralis. In addition to our work on the molecular and developmental biology of S. stercoralis, we maintain an interest in the biology of Dirofilaria immitis and in clinical management of canine and feline heartworm disease.

Rotation Projects for 2007-2008
1. Mobilizing transposable elements in the genome of Strongyloides stercoralis

2. Mechanisms of transgene inheritance and silencing in Strongyloides stercoralis

3. Structure and function of an insulin/IGF-class receptor kinase in Strongyloides stercoralis

4. Structure and function of an insulin/IGF-associated PI3 kinase in Strongyloides sterc oralis.

5. Structure and function of a TGF-beta superfamily growth factor in Strongyloides stercoralis.

Lab personnel:
• Holman Massey, Jr., Ph.D. – Research Specialist
• Xinshe Li, Ph.D. – Research Specialist
• Michelle Castelletto – Graduate Student, MVP