Theodore E. Nash, M.D.

Chief, Gastrointestinal Parasites Section

Description of Research Program

The laboratory deals primarily with gastrointestinal parasites. Most of the laboratory's activities involve studies of Giardia lamblia, but there is an interest in microsporidia, amoeba, cryptosporidia, isospora, and cyclospora. This laboratory discovered that Giardia undergoes surface antigenic variation, and there is continued interest in understanding the molecular mechanisms of surface antigenic variation and determining the function of the surface proteins that undergo antigenic variation. These proteins are highly unusual since they are cysteine-rich and contain zinc fingers. Using a previously developed adult mouse model of Giardia lamblia and a number of defined genetically deficient mice, we found that control of the acute infection is T cell mediated and not dependent upon change of surface antigens which is B cell dependent. Since Giardia is the most primitive eukaryote, understanding how Giardia performs basic cellular functions in comparison with higher eukaryotes has been helpful in elucidating the mechanisms present in more advanced cells. Stable transfection has been developed so that relevant genes, parts of genes or regulatory elements can be expressed in Giardia to understand how Giardia processes proteins, mechansims involved in gene regulation, and how Giardia replicates. The stable transfection system is being used to understand mechanisms involved in regulated cyst wall synthesis, how structural proteins such as ankyrins associate in Giardia, and requirements for initiation of transcription. A panel of monoclonal antibodies have been developed to Giardia and microsporidium which are useful as diagnostic reagents and answering cellular biology questions. A cDNA library to E. intestinalis has been produced and is being used to identify important microsporidium genes and proteins.

Memberships

• Infectious Diseases Society of America
• American Society of Tropical Medicine and Hygiene
• Royal Society of Tropical Medicine and Hygiene
• American Society of Microbiology
• Alpha Omega Alpha
• American Society of Protozology
• American Association for the Advancement of Science
• AMA

Research Group Members

John Conrad, Heidi Elmendorf, J. Russell Hayman, Sara Davis Hayman, Steve Singer

Selected Recent Publications

To view a complete listing, visit PubMed.

Lujan, H.D., Mowatt, M.R., Conrad, J.T., Bowers, B., and Nash, T.E. Identification of a novel Giardia lamblia cyst wall protein with leucine-rich repeats: implications for secretory granule formation and protein assembly into cyst wall. Journal of Biological Chemistry. 270: 29307-29314, 1995.

Lujan, H.D., Mowatt, M.R., Wu, J.J., Lu, Y., Lees, A., Chance, M.R., and Nash, T.E. Purification of a variant-specific protein of Giardia lamblia and characterization of its metal binding properties. Journal of Biological Chemistry. 270: 13807-13813, 1995.

Nash, T.E. and Mowatt, M.R. Variant-specific surface proteins of Giardia lamblia are zinc-binding proteins. Proceedings of the National Academy of Sciences USA. 90: 5489-5493, 1993.

Singer, S.M. and Nash, T.E. Episomal and integrated maintenance of foreign DNA in Giardia lamblia. Molecular Parasitology. 92: 59-69, 1998.

Nash, T.E. and Rice, W.G. Efficacies of Zinc-finger-active drugs against Giardia lamblia. Antimicrobial Agents and Chemotherapy. 42: 1488-1492, 1998.

Lujan, H.D., Mowatt, M.R., and Nash, T.E. The molecular mechanisms of Giardia encystation. Parasitology Today. 14: 446-450, 1998.

Special Interest Groups: Cell Biology, Structural Biology

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