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Cell and Molecular Biology Graduate Group


James B. Lok, Ph.D.

James B. Lok, Ph.D.
Professor of Parasitology, Dept of Pathobiology

Microbiology, Virology, and Parasitology Program


Address

Department of Pathobiology
430 Rosenthal Building
School of Veterinary Medicine
University of Pennsylvania
3800 Spruce Street
Philadelphia, PA 19104-6008

Office tel.: 215-898-7892
Lab tel.: 215-573-4756
Fax: 215-573-7023
E-mail: jlok@vet.upenn.edu

Link(s)

Dr. Lok's Veterinary School Faculty Page

Education

University of Southern Mississippi: BS (Biology), 1975.

Cornell University: MS (Entomology), 1979.

Cornell University: PhD (Entomology), 1981.

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.

PubMed Search
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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.

Recent Publications

Massey, HC Jr, Nishi M, Chaudhary K, Pakpour N and Lok JB. Structure and developmental expression of trongyloides stercoralisfktf-1, an ortholog of daf-16in Caenorhabditis elegans, a gene encoding a forkhead transcription factor necessary for dauer arrest. International Journal for Parasitology 2003; 33:1537-44.

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.

Massey HC, Bhopale MK, Li X, Castelletto M, Lok JB. The fork head transcription factor FKTF-1b from Strongyloides stercoralis restores DAF-16 developmental function to mutant Caenorhabditis elegans. Journal for Parasitology 2006; 36: 347-352.

Li X, Massey HC, Nolan TJ, Schad GA, Kraus K, Sundaram M, Lok JB. Successful transgenesis of the parasitic nematode Strongyloides stercoralis requires endogenous non-coding control elements. International Journal for Parasitology 2006; 36: 671-679.

Ashton, F.T, Zhu, X., Boston, R., Lok, J.B., Schad, G.A. Strongyloides stercoralis:amphidial neuron pair ASJ triggers significant resumption of development by infective larvae of under host-mimicking in vitro conditions. Experimental Parasitology 2007; 115:92–97.

Lab

Rotation Projects

  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
• Ariel Junio, M.S. – Research Specialist
• Michelle Castelletto – Graduate Student, MVP
 
last updated 8/2007
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