Julie Moore

Research

My research focuses on developing an understanding of how host/parasite interactions in malaria drive pathogenesis, with a particular emphasis on malaria during pregnancy. Malaria is a protozoal infection that is spread by Anopheles mosquitoes. In areas where malaria is transmitted year round, adult men and women develop an effective anti-disease immunity to malaria; that is, while they may harbor parasites in their blood circulation, they do not have symptomatic infections. When women become pregnant, however, their susceptibility to malaria increases dramatically. The hallmark of Plasmodium falciparum malaria during pregnancy is accumulation of parasite-infected red blood cells in the maternal blood space of the placenta (the intervillous space). This accumulation is associated with pathologic changes in the placental tissue and intrauterine growth restriction and low birth weight, conditions that seriously threaten the survival of newborns. Interestingly, these clinical conditions are worst in primigravidae (women in their first pregnancy); women gain the ability to control local parasitemia in the placenta over successive malaria-exposed pregnancies. In my laboratory, our current research aims to characterize malaria pathogenesis in the placenta, with the ultimate goal of providing novel diagnostic and therapeutic avenues for mitigating adverse fetal outcomes associated with placental malaria. To achieve this, we use a number of approaches ranging from epidemiological considerations of malaria in endemic populations to the cellular and molecular mechanisms of placental damage in mouse models and human in vitro cell culture systems.

For many years, I studied placental malaria in women living under intense malaria transmission conditions in Kisumu, western Kenya. Kisumu, located on the shores of Lake Victoria, is 10 kilometers south of the equator and is a malaria holoendemic area. In these studies, we recruited women at delivery, and performed intensive studies of the immunologic environment in the placenta, and how it differs from that in the peripheral blood of the parturient woman. We continue to use the expertise gained in these studies, and archived data and biological material to understand placental malaria pathogenesis.

While studies in human populations are critical for understanding the impact of malaria infection on the host, model systems are very useful for targeting cellular and molecular pathogenic mechanisms. In one such model system, we are investigating the role of the fetal syncytiotrophoblast (the cell in direct contact with maternal blood inside the placenta) in modulating maternal immune responses to placental malaria. These studies have shown that the syncytiotrophoblast is an active player in the placental immune environment, and that binding of cytoadherent P. falciparum-infected red blood cells to this fetal cell activates signaling pathways and immune gene expression and product secretion. These studies are relevant to our understanding of the complexities of maternal/fetal interactions during malaria infection and highlight the need to consider this forgotten half of the equation when developing malaria vaccine approaches and other immunotherapies. We are also using this model system to understand how placental malaria compromises fetal development and survival. The syncytiotrophoblast is critical in fetal/maternal exchange of nutrients and wastes; if the functions of this cell are disrupted, then the fetus is at risk for intrauterine growth restriction or even abortion or stillbirth. The syncytiotrophoblast system allows us investigate how malaria exposure disrupts its functions, and, how, in severe cases, this cell is irreparable harmed.

Finally, we have developed mouse models for studies of the immunopathogenesis of malaria-associated pregnancy loss, both in early pregnancy and late pregnancy. In areas of low malaria endemnicity, or where malaria occurs in epidemics, outcomes of malarial infection for both mother and infant are poor. Maternal death due to P. falciparum infection and abortion and stillbirth are common. Very little is known about the underlying causes of fetal loss in these circumstances. We have shown that maternal immune responses to malaria, particularly exaggerated cytokine responses, cause irreparable damage to the fetoplacental unit, resulting in fetal loss. We have also identified an important role for activation of blood coagulation in fetal loss. We are continuing to work toward identifying how these responses are initiated, and by what mechanisms trophoblast is compromised in both early and late pregnancy.

Finally, we have recently initated studies of cerebral malaria, the pathogenesis of which shares common features with placental malaria. Notably, both conditions are characterized by organ sequestration of malaria parasites, exaggerated coagulation, and inflammatory responses.

Courses Taught

IDIS(CBIO) 3100 and 3100H, People, Parasites, and Plagues: This undergraduate course takes a multi-disciplinary approach to examining the impact of infectious diseases on human populations. Epidemic (both past and present) and emerging diseases, and how they are identified, studied and combated, are discussed. Topics also include the sociological, psychological, historical, ecological and economic implications of infectious diseases. The course is intended primarily for non-science majors; however, science majors may also enroll. An Honors breakout section is available to those students who wish to explore these topics in more detail. Students are expected to master the concepts of disease, how scientific investigation is done, and the various mechanisms by which infectious diseases impact individuals and the societies in which they live.

Selected Publications

  1. Lucchi, N., Koopman, R., Peterson, D.S. and Moore, J.M. 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.  [PMID 16009422]
  2. Poovassery J., Moore J.M. 2006. Murine malaria infection induces fetal loss associated with accumulation of Plasmodium chabaudi AS-infected erythrocytes in the placenta.  Infection and Immunity, 74(5), 2839-48. [PMID: 16622222]
  3. Lucchi, N.W., Peterson, D.S., Moore, J.M. 2008. Immunologic activation of human syncytiotrophoblast by Plasmodium falciparum. Malaria Journal, 7:42-49.  [PMID 18312657]
  4. Perrault, S.D., Hajek, J., Zhong, K., Owino, S.O., Sichangi, M., Smith, G., Shi, Y.P., Moore, J.M., Kain, K.C.   Human immunodeficiency virus co-infection increases placental parasite density and transplacental malaria transmission in Western Kenya. American Journal of Tropical Medicine and Hygiene, 80(1), 119-25. [PMID: 19141849]
  5. Poovassery, J., Sarr, D., Smith, G., Nagy, T. and Moore, J.M. 2009. Malaria-induced murine pregnancy failure: distinct roles for IFN-gamma and TNF. J Immunol. 183(8):5342-9.  [PMID 19783682]
  6. Conroy, A., Serghides, L., Finney, C., Gowda, C.D., Liles, W.C., Moore, J.M., Kain, K.C. C5a potentiates dysregulated inflammatory and angiogenic responses associated with adverse birth outcomes in pregnancy-associated malaria.  PLoS ONE, 4(3): e4953. doi: 10.1371/journal.pone.0004953. [PMID: 19308263]
  7. Poovassery, J. and Moore, J.M. 2009. Association of malaria-induced murine pregnancy failure with robust peripheral and placental cytokine responses. Infect Immun. 77(11):4998-5006.  [PMID 19687196]
  8. Lucchi, N.W., Sarr, D., Owino, S.O., Mwalimu, S.M., Peterson, D.S., and Moore, J.M. 2011. Natural hemozoin stimulates syncytiotrophoblast to secrete chemokines and recruit peripheral blood mononuclear cells. Placenta. doi: 1016/j.placenta.2011.05.003 [PMID: 21632106]
  9. Iriemenam, N.C., Shah, M., Gatei, W., van Eijk, A.M., Ayisi, J., Kariuki, S., Vanden Eng, J., Owino, S.O., Lal, A.A., Omosun, Y.O., Otieno, K., Desai, M., ter Kuile, F.O., Nahlen, B., Moore, J.M., Hamel, M.J., Ouma, P., Slutsker, L., Shi, Y.P. 2012. Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. Malaria Journal. 11:134. doi:  1186/1475-2875-11-134. [PMID: 22540158].
  10. Sarr, D., Smith, G., Poovassery, J., Nagy, T. and Moore, J.M. 2012. Plasmodium chabaudi AS induces pregnancy loss in association with systemic pro-inflammatory immune responses in A/J and C57BL/6 mice. Parasite Immunology. 34(4):224-35. doi: 1111/j.1365-3024.2012.01355.x. [PMID: 22251385]
  11. Avery JW, Smith GM, Owino SO, Sarr D, Nagy T, Mwalimu S, Matthias J, Kelly LF, Poovassery JS, Middii J, Abramowsky C, Moore JM. 2012. Maternal malaria induces a procoagulant and antifibrinolytic state that is embryotoxic but responsive to anticoagulant therapy. PLoS ONE. 7(2): e31090. doi:1371/journal.pone.0031090. [PMID: 22347435]
  12. Moore, J.M. and Avery, J.W. 2012. Defibrotide: A Swiss Army Knife intervention in the battle against cerebral malaria. Arteriosclerosis, Thrombosis and Vascular Biology. 32(3):541-4. [PMID: 22345588]
  13. Sarr, D., Bracken, T.C., Owino, S.O., Cooper, C.A., Smith, G.M., Nagy, T. and Moore, J.M. 2015. Differential roles of inflammation and apoptosis in initiation of mid-gestational abortion in malaria-infected C57BL/6 and A/J mice. Placenta. 36(7):738-49. doi: 1016/j.placenta.2015.04.007. [PMID: 25956987]

 

Julie Moore
Professor, Department of Infectious Diseases
Associate Vice President for Research
706-542-5789
julmoore@uga.edu