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.
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.
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.
We have recently employed next-gen sequencing techniques to address the question of var2csa sequence diversity in placental malaria. Our preliminary work demonstrates a significant number (over 30 in some patient samples) of genetically unique sequence types. Surprisingly, we have also detected copy number variation in the var2csa gene that correlates with host immunity.
We have recently begun a collaboration with Dr. Eileen Kennedy in the Department of Pharmaceutical and Biomedical Sciences utiizing a relatively new class of inhibitors, chemically stabilized peptides, which are designed to target protein-protein interaction (PPI) interfaces. We are currently focusing our efforts on disrupting malarial kinases by targeting regulatory sites that exist only in P. falciparum kinases but are absent in the human kinome. We believe that this will lead to new strategies to exquisitely block fundamental processes that are required for malaria growth. In our initial work we are testing chemically stabilized peptides designed to specifically target P. falciparum kinases that are critical for parasite growth and virulence.
Finally we have an ongoing research interest in another protozoan parasite, Cytauxzoon felis, a tick transmitted parasite of cats causing a rapidly fatal febrile illness. We are using molecular techniques to study genetic variability in the parasite population. This work 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.
- Eldin Talundzic, Mussa Maganga, Irene M Masanja, David S Peterson, Venkatachalam Udhayakumar and Naomi W Lucchi Title : Field evaluation of the Photo-induced Electron Transfer Fluorogenic Primers (PET) real-time PCR for the detection of Plasmodium falciparum in Tanzania. Malaria Journal 2014, 13:31 doi:10.1186/1475-2875-13-31
- Patel JC, Oberstaller J, Xayavong M, Narayanan J, DeBarry JD, Srinivasamoorthy G, Villegas L, Escalante AA, DaSilva A, Peterson DS, Barnwell JS, Kissinger JC, Udhayakumar V and Lucchi NW (2013). Real-Time Loop-Mediated Isothermal Amplification (RealAmp) for the Species-Specific Identification of Plasmodium vivax. PLoS ONE 8(1): e54986. doi:10.1371/journal.pone.0054986
- Lucchi NW, Poorak M, Oberstaller J, DeBarry J, Srinivasamoorthy G, Goldman I, Xayavong M, da Silva AJ, Peterson DS, Barnwell JW, Kissinger J, Udhayakumar V. A new single-step PCR assay for the detection of the zoonotic malaria parasite Plasmodium knowlesi. PLoS One. 2012;7(2):e31848. PMID: 22363751
Talundzic, E., Shah,S., Fawole, O., Owino,S., Moore, J.M., Peterson,D.S. Sequence Polymorphism, Segmental Recombination and Toggling Amino Acid Residues within the DBL3X Domain of the VAR2CSA Placental Malaria Antigen. PLoS ONE 7(2): e31565. doi:10.1371/journal.pone.0031565.
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 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, Jul;20 (4):485-8 2008
- 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.