Neural crest cells as modulators of Wnt signalling in congenital heart disease:

Using genetic mouse models and RNA sequencing approaches, we have discovered that neural crest cells signal to cardiac progenitor cells during heart development to influence their differentiation potential. Current work is focussed on identifying the molecular signalling pathways responsible, with a major candidate being the Wnt signalling pathway. We are using embryo analysis, histology, advanced imaging, and stem-cell culture approaches to address how neural crest cells are influencing heart development, and how this can go wrong to cause congenital heart defects.

Mechanistic roles for neural crest cells in development of pulmonary stenosis:

Pulmonary stenosis is the narrowing of the pulmonary artery and valve, which normally provides the pathway for blood to leave the heart and flow to the lungs. Pulmonary stenosis is one of the most common congenital heart defects. We have discovered that Notch signalling ligands on cardiac neural crest cells signal to other cell types in the developing heart to influence the size and shape of the pulmonary valve and branching arteries. We are currently using state-of-the-art single cell RNA sequencing approaches to interrogate which cells are responding to Notch signalling, and the downstream pathways that can lead to abnormal pulmonary valve development.