Professor Paul Lehner

Extra-villous trophoblast (EVT) establish the critical interface between the developing fetal placenta and the maternal decidua. EVT play an essential role in the success of pregnancy with diseases of obstetric origin, such as pre-eclampsia often associated with poor EVT invasion. The unusual MHC molecule, HLA-G, modulates the maternal immune response to invasive placentation with HLA-G expression restricted to EVT. The regulation of HLA-G expression also provides important insights into EVT development.

Our work with trophoblast seeks to understand how EVT differentiate from cytotrophoblast progenitors, with HLA-G providing a milestone marker in their development. By applying CRISPR Cas9 genetic screens in human trophoblast stem cells we have identified essential transcription factors and epigenetic regulators involved in this process. Our studies provide unique insight into the regulation of these remarkable cells and open opportunities to understand their dysregulation in obstetric disease and how this can be remedied.