The overall goal of the research in the Bakardjiev lab is to understand the molecular and cellular mechanisms of host-pathogen interactions in the placenta that lead to premature labor, fetal damage and death. To understand our approaches one has to have a working knowledge of placental structure (see figure). The placenta has two functions: to nourish and to protect the fetus. Crucial for these functions are specialized fetally derived cells (trophoblasts), which differentiate into distinct subpopulations. Two trophoblast subpopulations are in direct contact with maternal blood and tissues: extravillous trophoblasts (EVT) and syncytiotrophoblasts (SYN). EVT invade the uterine implantation site where they are juxtaposed to maternal immune cells, suggesting that they play a role in facilitating tolerance of the fetal allograft. The SYN is bathed in maternal blood and is specialized to facilitate gas, nutrient and waste exchange between maternal and fetal circulation.


Structure and orientation of fetus and placenta in uterus.

(A) Structure and orientation of fetus and placenta in uterus. (B) Enlargement of boxed area in panel A. A continuous layer of multinucleated syncytiotrophoblasts (SYN) interfaces with maternal blood. At the uterine wall, extravillous trophoblasts (EVT) invade the uterus.



Pathogens in the maternal blood and uterus can colonize the placenta. This group of microbes consists almost exclusively of microbes with intracellular life cycles, such as the bacterial pathogen Listeria monocytogenes and the protozoan parasite Toxoplasma gondii. The Bakardjiev lab is using both of these pathogens to understand how pathogens colonize the placenta and breach the placental barrier. We have evidence that the trophoblast subpopulations in direct contact with maternal blood and uterus (SYN and EVT) have intrinsic defense mechanisms against infection. Nevertheless, L. monocytogenes and T. gondii are able to breach the placental barrier.


We are using cell biological, molecular genetic, and biophysical approaches to probe host-pathogen interactions at the maternal-fetal interface. We are interested in following questions:


1)    Which listerial virulence determinants are important for colonization of the placenta?

2)    How does L. monocytogenes disseminate from the intestine to the placenta?

3)    How does L. monocytogenes breach the placental barrier?

4)    What are the intrinsic host defense mechanisms of the placenta?