Development of immune competent 3D models of the MFI- The placenta as the primary organ of pregnancy, has to tightly regulate inflammation in order to maintain pregnancy. Accordingly, macrophages, pleiotropic antigen presenting cells with the capability to promote or restrict inflammatory signals to maintain tissue integrity, are the most abundant immune cell in the placenta. Yet, the mechanisms of innate immune regulation are unable to be validated in current models: Cell lines and organ on a chip models do not fully capture the innate immune activity and architecture of the placenta. Animal models are limited to different architecture of the placenta. The significant limits to extrapolate findings utilizing cell lines to the complexity of intact tissue has led to a major gap in understanding in placental immunology. The have led to a critical knowledge gap in our ability to test innate immune activity and defenses of the placenta. To overcome this we are developing 3D models of the placenta to model trophoblast-immune cell interactions and understand their relevance to pathogenesis.
Defining the relevance of fetal membrane macrophages- The FM is the initial fetal-derived tissue exposed to pathogens that ascend the genital tract. FMs are composed of an outer chorion and an inner amnion. Our work has identified a novel population of macrophages embedded in the human amnion during healthy pregnancy. This project seeks to understand the functional programming and relevance of this novel cell subset in maintaining the health of the fetal membranes as well as responding to bacterial pathogens
I lead a clinical and basic research program focused on understanding infection and immunity during pregnancy. Our research is directed towards filling knowledge gaps understanding innate immune regulation during pregnancy through rigorous research utilizing model systems, novel technologies and stringent clinical samples. In particular, we focus is on placenta innate immune responses to vertical pathogens, placental-myeloid cell regulation, how myeloid cell polarization alters responses during pregnancy and understanding the functional role of macrophage subsets in maintaining the health of the placenta. My lab uses multiple models of the human maternal-fetal interface including organoids, cell lines and fresh human placental explants.
Lab website- meglilab.com