Stephen Lye

My research studies have focused on the molecular mechanisms that responsible for pregnancy complications such as preterm birth, preeclampsia and IUGR as well as the influences of preconception, pregnancy and post-natal exposures on maternal child health and wellbeing. Our most recent work has defined how maternal decidual cells (including, uNK, vascular smooth muscle cells and endothelial cells) interact with trophoblast cells to support placental development and uterine vascular remodeling. We have also defined the role of maternal immune cells in the initiation of labor and have used this knowledge to develop predictive and diagnostic tests for preterm birth. We have defined pathways by which human labor is initiated in the presence of elevated circulating levels of progesterone – the molecular mechanism underlying a functional withdrawal of progesterone. These pathways involve the progesterone receptor isoform PRA which in the unliganded state becomes a transcriptional activator (rather than repressor) of labor genes. We are currently exploring two potential therapeutic agents in preclinical studies to prevent preterm labour. We have recently used Artificial Intelligence approaches to identify subtypes of preeclampsia and predict preeclampsia occurrence. Through cohort and clinical trials, we have sought to improve health and wellbeing of mothers and children through integrated and sustained interventions from preconception through childhood using a nurturing care framework first proposed through our Lancet Series on Early Child Development. We have applied our basic science and genetics expertise to identifying gene-environment interactions through which early life experiences have life-long and trans-generational impact on health and wellbeing.