Eleanor Ward

During early placental development, trophoblasts experience diverse metabolic challenges including an oxygen and nutrient limited microenvironment. While cellular metabolism is important for energy homeostasis and biosynthetic processes, it can also influence gene expression via modification of the epigenome. This is because epigenetic processes use metabolic intermediates as substrates and cofactors – for example acetyl-CoA is used in histone acetylation. 

I am particularly interested in nucleocytosolic acetyl-CoA production from acetate in human trophoblast stem cells. Acetate is a short chain fatty acid present in maternal circulation which is primarily produced by gut microbiota. Acetate and Coenzyme A can be utilised by Acetyl-CoA Synthetase enzymes (encoded by ACSS1 and ACSS2) to produce acetyl-CoA in the nucleus and cytosol. Clinical studies have also linked low serum acetate to pre-eclampsia during pregnancy. 

My research aims to establish mechanisms by which cellular metabolism directs epigenetic programs controlling human trophoblast stemness and differentiation in early placental development.