Ted Clark - Cornell Veterinary Medicine

Faculty

Theodore G. Clark

Associate Professor of Parasitology and Imunology

Cornell University College of Veterinary Medicine
C5163 Veterinary Medical Center
E-mail: tgc3@cornell.edu
Phone: 607-253-4042

PhD (SUNY at Stony Brook)

Dr. Clark joined the Department of Microbiology and Immunology as an Assistant Professor in 1996 and was promoted to Associate Professor in 2003. He is currently Director of Graduate Studies in the Graduate Field of Immunology and a member of the Aquatic Animal Health Program within the department. He received his BS from Columbia University in Bioengineering, and his PhD from the State University of New York at Stony Brook in Cell and Developmental biology. His research is supported by the NIH, NSF and USDA, and is directed towards a number of projects dealing with vaccine development, host-pathogen interactions, and the evolution of adaptive immunity.

Research Interests / Lab Members / Related Links / Selected References

Research Interests

Research in the Clark laboratory is focused in three mains areas. We have a long-standing interest in mechanisms of immune evasion and have worked extensively with Ichthyophthirius multifiliis, a parasitic protozoan of fish, as a model system. More recently, we have begun to develop the free-living pond-water ciliate, Tetrahymena thermophila, as a high-level protein expression system for vaccine antigens. Lastly, we are interested in the evolution of adaptive immunity and have turned to transgenic zebrafish models to examine sites of antigen-presentation in teleosts.

1. Mechanisms of immune evasion.

As the causative agent of “white spot”, I. multifiliis has substantial impact on commercial aquaculture worldwide. At the same time, it provides an extremely useful model for studies of host-parasite interactions, and the development of cutaneous immunity in lower vertebrates. A number of years ago, we showed that immunity against Ichthyophthirius involves a novel effect of antibody on parasite behavior. Rather than being killed, parasites are forced to exit fish prematurely in response to antibody binding. The target antigens in this case are abundant GPI-anchored proteins on the parasite surface known as i-antigens. The fact that premature exit requires antigen cross-linking (rather than antibody binding per se) has suggested a role for GPI-anchored proteins and lipid rafts in transmembrane signaling in I. multifiliis. Recently, we have found that lateral clustering of i-antigens at the parasite surface triggers a dramatic alteration of the lipid raft proteome, along with changes in serine/threonine and tyrosine phosphorylation of raft-associated proteins in ciliary and plasma membranes. These results clearly suggest that GPI-anchored proteins can transduce signals in protozoa and that raft mediated signaling evolved well before the emergence of metazoa. In connection with the parasite studies, a high-throughput sequencing project is currently underway to determine 36,000+ cDNA sequences from I.multifiliis at different stages of the parasite life cycle.

2. Tetrahymena as a high-level expression system for vaccine antigens.
On a more practical level, the laboratory has devoted considerable effort to the development of Tetrahymena thermophila, a free-living pond-water ciliate, as a novel platform for large-scale expression of eucaryotic membrane proteins. This includes candidate vaccine antigens from a number of parasitic protozoa (most notably Ichthyophthirius, and the human pathogen, Plasmodium falciparum), as well as drug targets for clinically important diseases of humans and animals. As part of these efforts, the Clark laboratory maintains an NIH-funded stock center for T. thermophila strains, and is involved in on-going efforts to physically map the Tetrahymena genome.

3. Evolution of antigen presentation.
As the earliest extant organisms in which adaptive immunity appeared, fish offer unique opportunities for studying the evolution of the acquired immune system. Despite this, almost nothing is known about antigen presentation in fish, and professional antigen-presenting cells have yet to be identified in teleosts. Comparative analyses reveal the presence of many homologs of mammalian DC markers in trout, catfish, fugu and zebrafish genomes. The laboratory is in the process of generating transgenic zebrafish that contain reporter genes driven by DC-specific promoters with the long-term goal of identifying and characterizing teleost DCs in vivo and in vitro, and determining their role in antigen presentation in fish.

Graduate Fields

Dr. Clark is a member of the following Graduate Fields:

Compartive Biomedical Sciences
Immunology

Lab Members

Elizabeth Bassity, Graduate Student
Yelena Bisharyan, Technical Support and Graduate Student
Donna Cassidy-Hanley, Senior Research Associate
Mossamal Hossain, Technical Support

Related Links

Aquatic Animal Health Program

"The Ich Page" at the University of Gerogia

Selected References

Lin, Y., Cheng, G., Wang, X., and T. G. Clark (2002). The use of synthetic genes for the expressions of ciliate proteins in heterologous systems. Gene. 288:85-94.

Lin, Y., Lin, T. L., Wang, C. C., Wang, X., Klobfleisch, R., Stieger, K., and T. G. Clark (2002). Variation in primary sequence and tandem repeat copy number among i-antigens of Ichthyophthirius multifiliis. Mol. Biochem. Parasitol. 120:93-106.

Orth, R. N., Kameoka, J., Zipfel, W. R., Ilic, B., Webb, W. W., Clark, T. G. and H. G. Craighead (2003). Creating biological membranes on the micron Scale: Forming patterned lipid bilayers using a polymer lift-off technique. Biophys. J. 85:3066-3073.

Bisharyan, Y., Chen, Q., Hossain, M. M., Papoyan, A., and T. G. Clark (2003). Cadmium effects on Ichthyophthirius: evidence for metal-sequestration in fish tissues following administration of recombinant vaccines. Parasitology 126:Suppl:S87-93.

Clark, T.G. and D. Cassidy-Hanley (2004). Recombinant subunit vaccines: Potential and constraints. Dev. Biol. Stand. 121:153-163.

Clark, T.G. (2005). Molecular approaches and techniques. In: Fish Diseases and Disorders, Volume 1: Protozoan and Metazon Infections. (ed. P.T.K. Woo, CABI Publishing, Oxon, U.K.).

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Last Revised on February 20, 2007