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Malaria: Rhoptries Are Specialized Organelles Found in Invasive Stages

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Malaria: Rhoptries Are Specialized Organelles Found in Invasive Stages TOBILI YVONNE SAM-YELLOWE Department of Biological, Geological and Environmental Sciences Cleveland State University Office: (216) 687-2068 Lab: (216) 687-2482 Fax: (216) 687-6972 E-mail: [email protected] Education: BS Microbiology, University of Oklahoma 1979 MS Microbiology, University of Oklahoma 1981 PhD Microbiology, University of Montana 1986 MPH Public Health, Cleveland State University 2009 Professional Experience: Postdoctoral Associate Biochemical Parasitology, The Rockefeller University, New York, NY (Laboratory of Dr. Margaret Perkins, 1986-1990). Professor of Biology Cleveland State University 1990 to present Adjunct Faculty Department of Immunology, Lerner Research Institute of the Cleveland Clinic Foundation. 1998 to present Faculty Department of Life Sciences, International Space University, Cleveland Summer Session, June 17-August 22, 1998. Topic: “Microbes and Microgravity” Teaching: Human Biology in Health and Disease Immunology Parasitology Histology Honors, Awards and Activities Fogarty International Center of the U.S., NIH, Minority International Training (MIRT) Program, University of Edinburgh, Edinburgh, Scotland UK 1996 Fogarty International Center of the U.S., NIH, Course on “Vectors and Vector Borne Diseases in Africa”, Bamako, Mali 1997 New England Biolabs Molecular Biology Summer Workshops, Smith College, Northampton, MA 2000 National Science Foundation Chautauqua Short Course “Updating Immunology” Whitehead Institute, Cambridge, MA 2001 National Institutes of Health (R21), 2005-2007 Cleveland State University Established Full-time Faculty Research Development Program (EFFRD), 2005-2007 Research Interests Malaria immunology, cell biology and molecular biology A major research area in my lab involves investigations of the role of rhoptry proteins in erythrocyte binding and invasion by Plasmodium merozoites. Investigations include: proteome analysis of the merozoite rhoptries, study of the immune response to rhoptry proteins & identification of determinants of blood stage immunity to Plasmodium in murine models, development of diagnostic biomarkers for malaria and mechanisms of the formation and function of the parasitophorous vacuole during intracellular blood stage development of Plasmodium. Rhoptries are specialized organelles found in invasive stages of Apicomplexan parasites such as in Plasmodium sp, the causative agent of malaria. Rhoptry proteins released during merozoite attachment and invasion into the host erythrocyte aid in the formation of the tight junction and parasitophorous vacuole. We investigated the composition of the rhoptry organelle using antibody production against isolated rhoptries and also by multidimensional protein identification technology (MudPIT) using isolated rhoptries. We identified novel proteins within the organelle that we are currently characterizing with the aim of identifying genes encoding proteins that participate in merozite invasion, parasitophorous vacuole formation, development of blood stage immunity and the identification of motifs critical to binding and host cell invasion shared among invasive stages (zoites) within the Apicomplexa. A second area of interest in the lab is macromolecular trafficking within the infected erythrocyte. We continue to investigate the Maurer’s clefts (MCs), structures that are formed as part of an elaborate intracellular membrane network in Plasmodium falciparum- infected red blood cells. Proteins destined to secretory compartments within the infected erythrocyte and to the surface of the infected erythrocyte are transported through this network. Using proteome analysis of immune complexes, we identified a novel multigene family; PfMC-2TM that encodes proteins located in the MCs. We continue to investigate this new gene family to understand the mechanisms of protein traffic within the infected erythrocyte, the role of PfMC-2TM proteins in protein traffic and formation & maintenance of the MCs during the blood stage of P. falciparum. Selected publications: 1. Sam-Yellowe, T. Y., Florens, L., Johnson, J. R., Wang, T., Drazba, J. A., Le Roch, K. G., Zhou, Y., Batalov, S., Carucci, D. J., Winzeler, E. A. and Yates, J. R. III. (2004) A Plasmodium gene family encoding Maurer’s cleft membrane proteins: Structural properties and expression profiling. Genome Research 14:1052-1059. 2. Sam-Yellowe, T. Y., Florens, L., Wang, T., Raine, J. D., Carucci, D. J., Sinden, R. and Yates. J. R. III (2004) Proteome analysis of rhoptry organelles isolated from Plasmodium merozoites. Journal of Proteome Research 3:995-1001. 3. Wang, T., Fujioka, H., Drazba, J. A. and Sam-Yellowe, T. Y. (2006) Rhop-3 protein conservation among Plasmodium species and induced protection against lethal P. yoelii and P. berghei challenge. Parasitology Research, Parasitol. Res. 99:238-252. 4. T. Sam-Yellowe, T. Wang, J. Tao, T. Banks, L. Everett, J. Drazba, and H. Fujioka (2006) Cloning of a Novel Plasmodium yoelii parasitophorous vacuole membrane gene. Proceedings of the 11th International Congress of Parasitology (ICOPA XI) August 6-11, 2006, page 571-576. 5. T. Banks, S. Gaines, N. Lovelace, H. Fujioka and T. Sam-Yellowe (2006) Novel Plasmodium yoelii merozoite rhoptry proteins. Proceedings of the 11th International Congress of Parasitology (ICOPA XI) August 6-11, 2006, page 251- 256. 6. Sam-Yellowe, T. Y., Banks, T. L., Fujioka, H., Drazba, J. A. and Yadav, S. P. (2008) Plasmodium yoelii: Novel rhoptry proteins identified within the body of merozoite rhoptries in rodent Plasmodium malaria. Exp. Parasitol. 120:113-117. 7. Tsarukyanova, I., Drazba, J. A., Fujioka, H., Yadav, S. and Sam-Yellowe, T. Y. (2009) Proteins of the Plasmodium falciparum two transmembrane Maurer’s cleft protein family, PfMC-2TM and the 130 kDa Maurer’s cleft protein define different domains of the infected erythrocyte intramembranous network. Parasitol. Res. 104:875-891. 8. Sam-Yellowe, T. Y. (2009) The role of the Maurer’s clefts in protein transport in Plasmodium falciparum. Trend Parasitol. 25:277-284. .
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