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| Research Interests |
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| 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 irk-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. |
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| Selected Publications : Search PubMed for articles |
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| Massey HC, Jr., Ball CC, Lok JB. PCR amplification of putative gpa-2 and gpa-3 orthologs from the (A+T)-rich genome of Strongyloides stercoralis. International Journal of Parasitology 2001; 31:377-383.
Lok JB, and Massey HC, Jr. Transgene expression in Strongyloides stercoralis following intragonadal microinjection of DNA constructs. Molecular and Biochemical Parasitology 2002; 119:279-284. Massey HC, Jr., Nishi M, Chaudhary K, Pakpour N, Lok JB. Structure and developmental expression of Strongyloides stercoralis fktf-1, an ortholog of daf-16 in Caenorhabditis elegans, a gene encoding a forkhead transcription factor necessary for dauer arrest International Journal of Parasitology 2003; 33:1537-1544. Lok JB, Knight DH, Nolan TJ, Grubbs ST, Cleale RM, Heaney K. Efficacy of an injectable, sustained-release formulation of moxidectin in preventing experimental heartworm infection in mongrel dogs challenged 12 months after administration. Veterinary Parasitology 2005;128:129-135. Massey HC, Jr, Castelletto ML, Bhopale VM, Schad G A, Lok JB. Sst-tgh-1 from Strongyloides stercoralis encodes a proposed ortholog of daf-7 in Caenorhabditis elegans. Molecular and Biochemical Parasitology 2005; 142: 116-120. |
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| Graduate Groups |
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| Cell and Molecular Biology (Microbiology/Virology/Parasitology track) |
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| Graduate Students |
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| Michelle Castelletto (CAMB/MVP) 2003-Present Beth Gregg (CAMB/MVP) - rotation student September-December, 2004 |
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