Stefan M. Kanzok
 | Assistant Professor Ph.D., 2001, University of Heidelberg, Germany Malaria Research Phone: 773.508.3790 Fax: 773.508.3646 E-Mail: skanzok@luc.edu |
RESEARCH INTERESTS
Human malaria is caused by the asexual multiplication of the protozoan parasite Plasmodium in the blood. Sexual differentiation or gametocytogenesis of the parasite is essential for the transmission into mosquitoes, which in turn facilitates the transfer of the parasite between human hosts. Recently, the genome of Plasmodium falciparum, the causative agent of the deadliest form of human malaria has been sequenced with the aim of initiating new approaches for the control of this vector borne disease. However, the function of approximately 60% of the 5,400 predicted genes remain unknown.In order to identify genes essential for sexual development and to put them into a functional context I will be employing a new technique recently adapted to the malaria parasite. Transposon-mediated insertional mutagenesis is a high throughput-tool for genomic manipulation. We have developed a flexible reporter-system for this technique focusing on genes essential for the development of Plasmodium gametocytes, the sexual stages.
The regulation of antioxidant genes during sexual development of Plasmodium is the focus of my work. These genes are involved in maintaining the vital redox equilibrium during and after transmission from the oxygen-poor surroundings in the vertebrate red blood cells to the oxygen-rich milieu of the insect midgut. These adjustments are critical in ensuring the successful establishment of the vector host cycle. Although a few genes, such as the thioredoxin and glutathione reductases, thioredoxin, and glutatredoxin have been characterized from the asexual stages their involvement in gametocytogenesis is poorly understood. Using this subset of described genes as a springboard for my research I hope to characterize the regulations of known and novel oxidative stress response genes and pathways during sexual development and transmission to the mosquito vector. Genes essential for these aspects of parasite biology represent attractive targets for disrupting disease transmission.
REPRESENTATIVE PUBLICATIONS
Kanzok S. M. and Jacobs-Lorena, M. (2006) Entomopathogenic fungi as biological insecticides to control malaria. Trends Parasitol; 22(2):49-51.Meister S., Kanzok S. M., Zheng X.-L., Luna C., Li T.-R., Hoa N. T, Clayton J. R., White K. P, Kafatos F. C., Christophides G. K and, Zheng L. (2005) Immune signaling pathways regulating bacterial and malaria parasite infection of the mosquito Anopheles gambiae. PNAS 102(32):11420-5.
Kanzok S. M., Hoa N. T., Bonizzoni M., Luna C., Huang Y., Malacrida A. R., Zheng L. (2004) Origin of Toll-like receptor-mediated innate immunity. Journal of Molecular Evolution 58(4):442-448.
Kanzok S. M. and Zheng L. (2003) The Mosquito Genome - A Turning Point? Trends in Parasitology 19(8):329-331. Review.
Becker K., Kanzok S. M., Iozef R., Fischer M., Schirmer R. H., Rahlfs S. (2003) Plasmoredoxin, a novel redox-active protein unique for malarial parasites. Euopean Journal of Biochemistry 270(6):1057-1064.
Luna C., Hoa N. T., Zhang J., Kanzok S. M., Brown S. B., Imler J.-L., Knudson D. L. and Zheng L. (2002) Characterization of Three Toll-like Genes from Mosquito Aedes aegypty. Insect. Biochem. Mol. Biol. 12(1):67-74
Christophides G. K., Zdobnov E., Barillas-Mury C., Birney E., Blandin S., Blass C., Brey P. T., Collins F. H., Danielli A., Dimopoulos G., Hetru C., Hoa N. T., Hoffmann J. A., Kanzok S. M., Letunic I., Levashina E. A., Loukeris T. G., Lycett G., Meister S., Michel K., Moita L. F., M?H.-M., Osta M. A., Paskewitz S. M., Reichhart J. M., Rzhetsky A., Troxler L., Vernick K. D., Vlachou D., Volz J., von Mering C., Xu J., Zheng L., Bork P., Kafatos F. C. (2002) Immunity-related genes and gene families in Anopheles gambiae. Science 298(5591):159-165.
Kanzok, S. M., Rahlfs, S., Becker, K., and Schirmer, R. H. (2002) Thioredoxin, thioredoxin reductase, and thioredoxin peroxidase of malaria parasite Plasmodium falciparum. Methods in Enzymology. 347:370-381.
Kanzok, S. M., Fechner, A., Bauer, H., Ulschmid, J. K., Botella-Munoz, J., Schneuwly, S., M? H. M., Schirmer, R. H., and Becker, K. (2001) Substitution of the Thioredoxin System for Glutathione Reductase in Drosophila melanogaster. Science 291 (5504); 643-646
Kanzok, S. M., Schirmer, R. H., T?ova, I., Iozef, R., and Becker, K. (2000) The Thioredoxin System of the Malaria Parasite Plasmodium falciparum - Glutathione Reduction revisited. Journal of Biological Chemistry 275 (51); 40180-40186
Fig. 1. The life cycle of the malaria parasite. When a mosquito takes a bloodmeal, parasites in the form of sporozoites are transmitted to humans. These parasites undergo asexual or sexual differentiation in the host. The mature forms of the parasite can be taken up in a mosquito bloodmeal where they further develop and consequently the cycle of infection perpetuates.
Fig. 2. Oocysts: Oocysts of the Malaria parasite P. falciparum on Mosquito (A. Stephensi) midgut 8 days after infectious bloodmeal.