Research summary

The aim of my research is to understand the mechanisms that govern endometrial function in the context of reproductive health and disease. It combines fundamental investigations into endometrial cell biology with a strong translational focus, centred on developing strategies for the prediction and prevention of early and late pregnancy disorders.

My studies have unraveled how progesterone signaling coordinates endometrial differentiation (decidualization) and resulted in the discovery of key decidua-specific transcription factors and signalling pathways. Furthermore, my work demonstrated that decidual cells play a critical role in maternal selection of implanting embryos. Importantly, I also showed that aberrant decidualization, the hallmark of recurrent miscarriages, disables this selectivity checkpoint, leading to prolonged maternal investment in a failing pregnancy. The most important driver of my translational work, however, was the discovery that isolated endometrial cells, even in prolonged culture, continue to phenocopy the aberrant tissue responses that cause pregnancy failure.

These observations indicate that the likelihood of successful or unsuccessful pregnancy outcome is largely determined prior to conception. Understanding the nature and mechanisms that underpin the ‘programming’ endometrial cells is a major theme in my lab.

The translational challenge now is to develop and trial pre-pregnancy tests that identify patients at increased risk of early pregnancy loss.

Selected publications:

• Loss of Endometrial Plasticity in Recurrent Pregnancy Loss. Stem Cells. 2015 Sep 29. doi: 10.1002/stem.2222.
• Muter J, Lucas ES, Chan YW, Brighton PJ, Moore JD, Lacey L, Quenby S, Lam EW, Brosens JJ. The clock protein period 2 synchronizes mitotic expansion and decidual transformation of human endometrial stromal cells. FASEB J. 2015 Apr;29(4):1603-14. doi: 10.1096/fj.14-267195
• Salker MS, Christian M, Steel JH, Nautiyal J, Lavery S, Trew G, Webster Z, Al-Sabbagh M, Puchchakayala G, Föller M, Landles C, Sharkey AM, Quenby S, Aplin JD, Regan L, Lang F, Brosens JJ. Deregulation of the serum- and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failure. Nat Med. 2011 Oct 16;17(11):1509-13. doi: 10.1038/nm.2498.
• Regulation of the SUMO pathway sensitizes differentiating human endometrial stromal cells to progesterone. Jones MC, Fusi L, Higham JH, Abdel-Hafiz H, Horwitz KB, Lam EW, Brosens JJ. Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16272-7.