Research
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.
Publications
Seczynska M, Bloor S, Cuesta SM, Lehner PJ. Genome surveillance by HUSH-mediated silencing of intronless mobile elements. Nature. 2022 601(7893):440-445. doi: 10.1038/s41586-021-04228-1. PMID:34794168; PMCID: PMC8770142
Seczynska M, Lehner PJ. The sound of silence: mechanisms and implications of HUSH complex function. Trends in Genetics 2023 Feb 6:S0168-9525(22)00314-6. doi: 10.1016/j.tig.2022.12.005. PMID: 36754727.
Dickson AS, Pauzaite T, Arnaiz E, Ortmann BM, West JA, Volkmar N, Martinelli AW, Li Z, Wit N, Vitkup D, Kaser A, Lehner PJ, Nathan JA. A HIF independent oxygen-sensitive pathway for controlling cholesterol synthesis. Nat Commun. 2023 Aug 9;14(1):4816. doi: 10.1038/s41467-023-40541-1. PMID: 37558666; PMCID: PMC10412576.
