345c Coverdell Center
376 Coverdell Center
|Erythrocytes containing late stage malaria parasites|
There are several interrelated research areas within my laboratory, most of which are focused on the parasite Plasmodium falciparum, a causative agent of human malaria. We are interested in the role of adhesion proteins of the DBL-domain superfamily. Members of this superfamily play diverse roles, functioning both as ligands for erythrocyte receptors during host red cell invasion, and as cytoadherence proteins during sequestration of the parasite throughout the vasculature. We have previously defined new members of this family, and found evidence of host selective pressure acting on one of the genes. Current research efforts include work to produce some of the erythrocyte binding proteins in a novel expression system for detailed study. This expression system utilizes the free-living protozoan Tetrahymena thermophila which we have previously demonstrated to be capable of expression of the full-length circumsporozoite protein of P. falciparum.One research effort in the lab, in collaboration with the laboratory of Dr. Julie Moore, is to examine how the binding of parasite infected erythrocytes (IE) to host cells in the vasculature and the placenta can affect host cell function, and potentially modulate the host immune response. Sequestration of IE occurs through direct interaction between PfEMP1 on the surface of the IE and receptors present on vascular endothelial cells, or in the case of placental sequestration, to a unique low-sulfated form of chondroitin sulfate A within the intervillous space. In previous work we have shown that binding of IE to placental syncytiotrophoblasts induces intracellular signaling and release of MIF.
|Var2csa DBL3-x sequences, color coded by patient sample, illustrated the significant diversity within the parasite population.|
In other collaborative work with Dr. Julie Moore we are characterizing the sequence diversity within the var2csa gene. This member of the var gene family is specifically expressed on the surface of IE sequestered in the placenta of pregnant women. While more conserved than other members of the highly diverse var gene family, this gene still exhibits considerable sequence polymorphism, suggesting that it is under significant diversifying selective pressure. With the ultimate goal of understanding the development of immunity to placental parasites expressing var2csa, our current work has begun to define the degree of sequence diversity present in this var gene in parasite isolates obtained from women with placental malaria in a highly endemic region of Kenya.
Another protozoan parasite that we are actively studying is Cytauxzoon felis, a tick transmittedprotozoan parasite of cats causing a rapidly fatal febrile illness. We are using molecular techniques to study genetic variability in the parasite populaion. In this study, we are using sequence analysis to determine if C. felis-infected animals were infected with genetically similar parasites or if there is significant genetic diversity within the parsite population. Our immediate objective is to identify changes in the nucleic acid sequence of the ribosomal internal transcribed spacer regions (ITS) of Cytauxzoon felis from infected feline blood samples. Sequence data is assessed in regard to clinical outcome to determine if there are any linkages between particular parasite genotypes and observed pathogenicity. This study may provide the means to identify particularly pathogenic strains of C. felis and subsequently assist the clinician in choosing treatment options. Greater understanding of why some domestic cats survive C. felis infection while others do not may enhance our ability to prevent or treat this highly fatal infectious disease.
|Schizont-laden macrophages occlude the lumen of a large vessel from a cat with fatal cytauxzoonosis.|
Lucchi, N.W., Sarr, D., Owino, S.O., Mwalimu, S.M., Peterson, D.S., Moore, J.M. Natural Hemozoin Stimulates Syncytiotrophoblast to Secrete Chemokines and Recruit Peripheral Blood Mononuclear Cells. Placenta 2011 Aug;32(8):579-85. PMID: 21632106
Demas A, Oberstaller J, Debarry J, Lucchi NW, Srinivasamoorthy G, Sumari D, Kabanywanyi AM, Villegas L, Escalante AA, Kachur SP, Barnwell JW, Peterson DS, Udhayakumar V, Kissinger JC..Applied genomics: Data mining reveals species-specific malaria diagnostic targets more sensitive than 18S rRNA . J Clin Microbiol 2011 Jul;49(7):2411-8 PMID: 21525225
Shock, BC, SM Murphy, LL Patton, PM Shock, C Olfenbuttel, J Beringer, S Prange, DM Grove, M Peek, JW Butfiloski, DW Hughes, JM Lockhart, SN Bevins, S Vandewoude, KR Crooks, VF Nettles, HM Brown, DS Peterson, MJ Yabsley. 2011. Distribution and prevalence of Cytauxzoon felis in bobcats (Lynx rufus), the natural reservoir, and other wild felids in thirteen states. Veterinary Parasitology 175: 325-330.
Brown, H.M., Lockhart, J.M., Latimer, K.S., Peterson, D.S. Identification and genetic characterization of Cytauxzoon felis in asymptomatic domestic cats and bobcats. Vet Parasitol 2010 Sep 20;172(3-4):311-316 PMCID: 20605334
Githui, E.K., Peterson, D.S., Aman, R.A., Abdi A.I. Prevalence of 5’ Insertion mutants and analysis of single nucleotide polymorphism in the erythrocyte binding-like 1 (ebl-1) gene in Kenyan Plasmodium falciparum field isolates. Infect. Genet. Evol., 2010 Aug; 10(6):834-9 PMCID: 19879379
Brown, H. M., Modaresi, S. M., Cook, J. L., Latimer, K.S., Peterson, D.S. "Genetic variability of archived Cytauxzoon felis histologic specimens from domestic cats in Georgia, 1995-2007" Journal of Veterinary Diagnostic Investigation, 2009 Jul;21(4):493-8 PMID: 19564497
Brown, H. M., Berghaus, R.D., Latimer, K.S., Britt, J.O., Rakich, P.M., Peterson, D.S. Genetic variability of Cytauxzoon felis from 88 infected domestic cats in Arkansas and Georgia. Journal of Veterinary Diagnostic Investigation, 2009 Jan;21(1):5963 PMID: 19139502
Brown, H. M., Latimer, K.S., Erikson, L.E., Britt, J.O., Peterson, D.S. Detection of persistent Cytauxzoon felis infection by polymerase chain reaction in three asymptomatic domestic cats. Journal of Veterinary Diagnostic Investigation, In Press, 2008
Nielsen, M, K., Peterson, D.S., Monrad, J., Thamsborg, S.M., Olsen, S. N., Kaplan, R. M. Detection and semi-quantification of Strongylus vulgaris DNA in equine faeces by real-time PCR, International Journal for Parasitology, 2008 Mar;38(3-4):443-53
Lucchi, N. W., Peterson, D.S., Moore, J.M. Immunologic Activation of Human Syncytiotrophoblast by Plasmodium falciparum, Malaria Journal 2008, 7:42,
Bostrom, B., Wolf, C., Greene, C., Peterson, D.S. Sequence conservation in the rRNA first internal transcribed spacer region of Babesia gibsoni genotype Asia isolates, Veterinary Parasitology, 152 (1-2):152-157, 2008
Lucchi, N., Koopman, R., Peterson, D. S. and Moore, J. M. 2006. Plasmodium falciparum-Infected Red Blood Cells Selected For Binding To Cultured Syncytiotrophoblast Bind to Chondroitin Sulfate A And Induce Tyrosine Phosphorylation In the Syncytiotrophoblast. Placenta, 27(4-5):384-94.
Drummond, P. B. and Peterson, D. S. 2005. An analysis of genetic diversity within the ligand domains of the Plasmodium falciparum ebl-1 gene. Molecular and Biochemical Parasitology, 140(2):241-5.
Chaisavaneeyakorn, S., Lucchi, N., Abramowsky, C., Othoro, C., Chaiyaroj, S. C., Shi, Y. P., Nahlen, B. L., Peterson, D. S., Moore, J. M. and Udhayakumar, V. 2005. Immunohistological Characterization of Macrophage Migration Inhibitory Factor (MIF) Expression in Malaria-Infected Placenta. Infection and Immunity, 73(6):3287-93.