Christine Carr Dykstra, PHD

My research program has both a basic and applied aspect towards the study of infectious diseases. It is centered on the utilization of novel therapeutic agents for the identification and analysis of their targets in order to develop an increased knowledge of both the disease-causing organism and how the novel agent exerts its activity. My area of expertise gained from my training is in DNA-dependent enzymes and the molecular analysis of their genes. Because of this expertise, my major efforts are and will continue to be the analysis of therapeutic agents that exert their action through DNA-dependent enzymes. We are currently working in the laboratory on numerous organismsfrom E. coli to S. cerevisiae as well characterized models and with numerous pathogens to test our theories. These include parasites and fungi that are important opportunistic pathogens or emerging diseases (Cryptosporidium parvum, Giardia lamblia, Toxoplasma gondii, Neospora caninum, Cryptococcuss neoformans, and Candida albicans). Because the opportunistic pathogens are not well characterized genetically, we have devoted some time to trying to better understand their biological niches. My current funding includes one of the projects in a program project grant from the NIH to study mechanisms of action of dicationic molecules under development for treatment of opportunistic infections. This is the core around which my other projects have evolved. I have industrial funding to investigate drug effects on the integrase protein from HIV-1. There is funding from the USDA to analyze differences between pathogenic and non-pathogenic Cryptosporidium species and to use this knowledge to develop a specific test for pathogenic organisms in nature. There is corporate/Auburn University internal funding in a joint venture to identify new therapeutic targets in Toxoplasma and Giardia.

Cox, G.M., Rude, T.H., Dykstra, C.C., and Perfect, J.R. The actin gene from Cryptococcus neoformans: Structure and phylogenetic analysis. Journal of Human and Veterinary Mycology, 33:261-266, 1995.

*Christopher, L.J., *Fletcher, L.D., and Dykstra, C.C. Cloning and identification of ARP1, an actin-related protein from Pneumocystis carinii. Journal of Eukaryotic Microbiology, 42:142-149, 1995.

Boykin, D. W., Kumar, A. Spychala, J., Zhou, M., Lombardy, R.J., Wilson, W.D., Dykstra, C.C., Jones, S.K., Hall, J.E., Tidwell, R.R., Laughton, C., Nunn, C.M., and Neidle, S. Dicationic diaryl Furans as Anti-Pneumocystis carinii Agents. Journal of Medicinal Chemistry, 38:912-916, 1995.

Spychala, J., Boykin, D.W., Wilson, W.D., Zhao, M., Tidwell, R.R., Dykstra, C.C., Hall, J.E., Jones, S.K., and Schinazi, R.F. Synthesis of Dicationic Diaryltriazines: Nucleic Acid Binding Agents. Journal of European Medicinal Chemistry 29:363-367, 1994.

Kumar, A.,Rhoades, R.A., Spychyla, J., Wilson, W.D., Boykin, D. W., Tidwell, R.R., Dykstra, C.C., Hall, J.E., Jones, S.K., and Schinazi, R.F. Synthesis of dicationic diarylpyridines as nucleic acid binding agents. European Journal of Medicinal Chemistry, 30:99-106, 1995.

Dykstra, C.C., McClernon, D., Elwell, L., and Tidwell, R.R. Selective inhibition of topoisomerases from Pneumocystis carinii versus mammalian topoisomerases by dicationic bis-benzimidazoles. Antimicrobial Agents and Chemotherapy, 38:1890-1898, 1994.

*Fletcher, L.D., McDowell, J.D., Meagher, R.B., Tidwell, R.R., and Dykstra, C.C. Structure, expression and phylogenetic analysis of the gene encoding Actin I from Pneumocystis carinii. Genetics. 137:743-750, 1994.

Weinberg, Geofferey, A., Dykstra, Christine C., Durant, Pamela J., and Cushion, Melanie T. Chromosomal gene assignment of 20 distinct genes to 5 gentically diverse pulsed field karyotypes of rat Pneumocystis carinii. Journal of Eukaryotic Microbiology 41:117S, 1994.

*Christopher, L.J. and Dykstra, Christine C. Identification of a type II topoisomerase gene from Cryptosporidium parvum. Journal of Eukaryotic Microbiology 41:28S, 1994.

Bell, C.A., Dykstra, C.C., Naiman, N.A.,Cory, M., Fairley, T.A., and Tidwell, R.R. Structure-activity studies of dicationically substituted bis-benzimidazoles against Giardia lamblia: Correlation of antigiardial activity with DNA binding affinity and giardial topoisomerase II inhibition. Antimicrobial Agents and Chemotherapy, 37:2668-73. 1993.

*Fletcher, L.D., Tidwell, R.R. and Dykstra, C.C. Cloning and characterization of the calmodulin-encoding gene from Pneumocystis carinii. Gene.129:307-308, 1993.

*Fletcher, L.D., *Berger, L.C., Peel, S.A., Baric, R.S.,Tidwell, R.R., and Dykstra, C.C. Isolation and identification of six Pneumocystis carinii genes utilizing codon bias. Gene, 129:167-174, 1993.

Tidwell, R.R., Jones, S.K., Naiman, N.A., *Berger, L.C., Brake, W.B., Dykstra, C.C., and Hall, J.E. Activitiy of cationically substituted bis-benzimidazoles against experimental Pneumocysitis carinii pneumonia. Antimicrobial Agents and Chemotherapy, 37:1713-1716, 1993.

Approved:

Boykin, D.W., Dykstra, C.C., Tidwell, R.R., Hall, J.E., Wilson, W.D., and Kumar, A. "Methods of Treating Pneumocystis carinii pneumonia". Filed September 13, 1994. Approved May 28, 1996, Serial No. 5,521,189. 25%

Tidwell, R.R., Dykstra, C.C., and Hall, J.E. "Methods of combating Pneumocystis carinii pneumonia and compounds useful therfor" Filed October 13, 1992. Approved June 27, 1995 , Serial No. 07/958,696. 30%

Dykstra, C.C., Tidwell, R.R., Boykin, D. W., and Wilson, W.D. "Method of Fluorescent Detection of Nucleic Acids and Cytoskeleton Elements Using Bis-dicationic, Aryl Furans". Continuation in part application, Filed June 7, 1995. 08/485,381. Notice of Allowance October 2, 1996. 45%

Filed:

Tidwell, R.R., Hall, J.E., Boykin, D.W., Dykstra, C.C., Perfect, J. and Blagburn, B. "Methods of Treating Microbial Infections". filed June 7, 1995, 08/477,876.

Dykstra, C.C., Perfect, J., Boykin, D.W., Wilson, W. D., and Tidwell, R.R. "Dicationic, aromatic molecules as anti-fungal agents". filed June 7, 1995, 08/472,996.

Tidwell, R.R., Dykstra, C.C., and Hall, J.E. "Methods of combating Pneumocystis carinii pneumonia and compounds useful therfor" Divisional application Filed April 24, 1995. #08/427,597.

Boykin D.W., Dykstra, C.C., Tidwell, R.R., Hall, J.E., Wilson, W.D., Blagburn, B.L. and Kumar, A. Methods of inhibiting Pneumocystis carinii pneumonia, Giardia lamblia, and Cryptosporidium parvum, and compounds useful therefor". filed November 13, 1994. 08/339,487.

Dykstra, C.C., Tidwell, R.R., Boykin, D.W., Wilson, W.D., Spychala, J., Das, B.P., and Kumar, A. "Method of Fluorescent Detection of Nucleic Acids and Cytoskeleton Elements Using Bis-Dicationic, Aryl Furans," filed May 6, 1994. 08/238,766.

Dykstra, C.C., Tidwell, R.R., and Swanstrom, R.I. "Method of inhibiting retroviral integrase" Filed Jan 20, 1994. 08/185,079.