Dr Dafina Angelova

Tight junctions are the seals between cells which control what passes between them. They are important in keeping the inside in and the outside out. My research focuses on understanding the role of tight junctions in the development of the placenta, the organ that nourishes a growing fetus. Specifically, I'm interested in the dynamics of tight junctions in trophoblasts, the key cells of the placenta. I will study human trophoblast stem cells, which are able to proliferate and also turn into two types of trophoblast cells in the placenta – a fused syncytiotrophoblast and an invasive extravillous trophoblast. In very early stages of development, trophoblast cells have stable tight junctions which must break down for the placenta to develop. If the placenta is insufficiently developed the nutrient and gas exchange between mother and baby is compromised, increasing their risk of pregnancy complications, including pregnancy loss.

I plan to investigate a specific tight junction protein called CXADR. I hypothesise that CXADR and its interacting proteins play a crucial role in how these cells differentiate. My approach involves using CRISPR gene editing to create human trophoblast stem cells that have either too much or too little CXADR. If I remove or add more CXADR, I believe this will alter the cells’ behaviour resulting in improper differentiation. I will also identify which proteins CXADR works with to achieve these effects and how its production, breakdown and location in the cell is controlled.

The project will further the theoretical understanding of the role of tight junctions and the contribution of the CXADR protein to placental development. Together, these lines of research will allow us to better define what makes a pregnancy healthy and what mechanisms could be employed for the prevention of pregnancy complications.