Biomedical Graduate Studies

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.


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

Description of Research
The Lok lab's primary interest is the endogenous mechanisms 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 and S. ratti 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 testing this hypothesis we have determined that genes encoding key elements of the C. elegans insulin/IGF pathway are conserved in Strongyloides spp. We are now using C. elegans as a genetic surrogate to assess function of Strongyloides daf-2, age-1 and daf-16, orthologs of the insulin receptor, PI3 kinase 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. We are also developing a system for transgenesis in Strongyloides spp. and are now using it to study functions of these genes using transgene-encoded dominant mutations predicted to confer gain or loss of function in insulin-like signaling molecules. In addition to our work with insulin-like signaling, we have also determined that S. stercoralis has also conserved elements of three other signal transduction pathways that regulate dauer development in C. elegans, a steroid nuclear hormone receptor (NHR) pathway, a G protein-mediated odorant receptor pathway and a TGF-ß-like signal pathway. We are currently investigating links between the insulin-like and DAF-12 NHR signaling. The steroid ligands of Ss-DAF-12 are being evaluated as drug candidates in Strongyloides infection.


Rotation Projects
1. Mobilizing transposable elements in the genome of Strongyloides spp.

2. Developmental function of the DAF-12 nuclear hormone receptor in Strongyloides spp.

4. Structure and function of a TGF-beta superfamily growth factor in Strongyloides spp.


Lab personnel:

• Holman Massey, Jr., Ph.D. – Research Specialist
• Xinshi Li, M.D. – Research Specialist
• Hongguang Shao, Ph.D. – Research Specialist
• Najju Ranjit, Ph.D. – Postdoctoral Fellow
• He Zhu, Ph.D. – Postdoctoral Fellow
• Jonathan Stoltzfus – Predoctoral Student
• Beth Maguire – Lab Manager/Technician
• Sara Haus – Technician