Select Faculty Member Mark R. Brown Donald E. Champagne Daniel G. Colley Harry W. Dickerson, Jr. Roberto Docampo Stephen L. Hajduk Jessica Kissinger Patrick J. Lammie Kojo A. Mensa-Wilmot Julie M. Moore Silvia N.J. Moreno Ynes R. Ortega David S. Peterson Pejman Rohani Robert Sabatini Mike R. Strand Boris Striepen Rick L. Tarleton

Associate Professor
Department of Infectious Diseases
BS, St. Lawrence University, 1987
PhD, University of Connecticut Health Center, 1995

E-mail: julmoore@vet.uga.edu
Telephone: 706-542-5789

Research
My research focuses on developing an understanding of immunoprotective and immunopathogenic processes in infections during pregnancy. For the past ten years, we have worked on understanding immunity to malaria at the placental level 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. Malaria, which is a protozoal infection that is spread by Anopheles mosquitoes, is transmitted year round in this region. Under these conditions, adult men and women develop an effective anti-disease immunity to malaria; 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 malaria during pregnancy is accumulation of malarial 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 intra-uterine growth retardation 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. By performing in depth studies of maternal cell-mediated in the intervillous blood, we are working to understand how this gravidity-dependent resistance to placental malaria develops and is maintained over successive pregnancies, with a particular focus on T cell memory responses. Our human studies also focus on the interaction between malaria and HIV during pregnancy. Although it is not so obvious in other groups, malaria is clearly an opportunistic infection in HIV-infected pregnant women, well before their immune system weakens to the point that other more common opportunistic infections take hold. In western Kenya, close to 30% of reproductive age-women are infected with HIV. We are working to understand how HIV impacts immunity to malaria and how changes in immunity in the placenta may influence transmission of the virus from mother to fetus/infant.

In another ongoing project, 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.

Finally, we have developed a mouse model for studies of the immunopathogenesis of malaria-associated pregnancy loss. 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 hypothesize that maternal immune responses to malaria, particularly exaggerated cytokine responses, cause irreparable damage to the fetoplacental unit, resulting in fetal loss. We are currently performing detailed studies using antibody ablation and gene knock-out mice to identify those maternal factors that contribute to failure of pregnancy during malarial infection.

Courses Taught

PARA(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. Honors and discussion group sections are 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.

Representative Publications

Moore, J.M., Nahlen, B., A.A. and Udhayakumar, V. Immunologic memory in the placenta: A lymphocyte recirculation hypothesis. 2000. Medical Hypotheses, 54(3), 505-10.

Moore, J.M., Nahlen, B., A.A. and Udhayakumar, V. Immunity to placental malaria. II. Placental antigen-specific cytokine responses are impaired in human immunodeficiency virus-infected women. 2000. Journal of Infectious Diseases, 182(3), 960-4.

Chaisavanneyakorn, S., Moore, J.M., Otieno, J., Chaiyaroj, S.C., Perkins, D.J., Shi, Y.P., Nahlen, B.L., Lal, A., and Udhayakumar, V. Immunity to placental malaria. III. Impairment of interleukin(IL)-12, not IL-18, and interferon-inducible protein-10 responses in the placental intervillous blood of human immunodeficiency virus/malaria-coinfected women. 2002. Journal of Infectious Diseases, 185(1), 127-31.

Chaisavanneyakorn, S., Moore, J.M., Otieno, J., Chaiyaroj, S.C., Perkins, D.J., Shi, Y.P., Nahlen, B.L., Lal, A., and Udhayakumar, V. Immunity to placental malaria. IV. Placental malaria is associated with up-regulation of macrophage migration inhibitory factor in intervillous blood. 2002. Journal of Infectious Diseases, 186(9), 1371-5.

Moore, J.M., Shi,Y.P, Othoro, C., Nahlen, B.L., Lal, A.A, and Udhayakumar, V. Comparative flow cytometric analysis of term placental intervillous and peripheral blood from immediate postpartum women in western Kenya. 2003. Placenta, 24, 779-85.

Chaisavanneyakorn, S., Moore, J.M., Mirel, L., Othoro, C., Otieno, J., Chaiyaroj, S.C., Shi, Y.P, Nahlen, B.L., Lal, A.A, and Udhayakumar, V. Levels of macrophage inflammatory protein 1 alpha (MIP-1 alpha) and MIP-1 beta in intervillous blood plasma samples from women with placental malaria and human immunodeficiency virus infection. 2003. Clinical and Diagnostic Laboratory Immunology, 10(4), 631-6.

Perkins, D.J., Moore, J.M., Otieno, J., Shi, Y.P., Nahlen, B.L., Udhayakumar, V., Lal A.A. 2003. In vivo acquisition of hemozoin by placental blood mononuclear cells suppresses PGE2, TNF-alpha, and IL-10. Biochemical and Biophysical Research Communications, 311(4), 839-46.

Moore, J.M., Chaisavanneyakorn, S., Perkins, D.J., Otieno, J., Nahlen, B.L., Shi, Y.P., Udhayakumar, V. 2004. Hemozoin differentially regulates proinflammatory cytokine production in human immunodeficiency virus-seropositive and - seronegative women with placental malaria. Infection and Immunity, 72(12), 7022-9.

Chaisavanneyakorn, 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 expression in Plasmodium falciparum-infected placentas. Infection and Immunity, 73(6):3287-93.

Ned, R.M., Moore, J.M., Chaisavaneeyakorn, S. and Udhayakumar, V. 2005. Modulation of immune responses during HIV/malaria co-infection in pregnancy. Trends in Parasitology, 21(6):284-91.Lucchi, N., Koopman, R., Peterson, D.S. and Moore, J.M. 2005. Plasmodium falciparum-infected red blood cells selected for binding to cultured syncytiotrophoblast bind to chondroitin sulfate A and induce tyrosine phosphorylation in the syncytiotrophoblastPlacenta, in press.

Lucchi, N., Koopman, R., Peterson, D.S. and Moore, J.M. 2005. 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, in press.