I have dual training, both as a paediatric intensivist and in also in developmental molecular genetics. Over the last few years I have gradually moved from the hospital intensive care unit into the University laboratory to pursue biomedical research. I am interested in inherited cardiac diseases that are present at birth, and usually structural , but also in other diseases, such as cardiomyopathy that develop later in life. Both knockout (Cre-lox) mice and zebrafish are used in these studies and a variety of molecular, genomic and proteomic approaches are used in this work.
Over the last decade Deb Henderson and I have been investigating how the heart forms using knockout mice and zebrafish. We have particularly focussed on Vangl2, a gene in the non-canonical Wnt signalling or planar cell polarity (PCP) pathway. The Looptail mouse, a naturally occurring Vangl2 mutant, has taught us a great deal about how the outflow tract (the aorta and pulmonary artery) develops and we are now examining if the developmental origins of these great vessels might be linked with adult onset disease. I work closely with Bob Anderson and especially try to link developmental cardiac morphology with molecular genetic approaches. I have also been looking at the possibility of modelling cardiomyopathy in adult zebrafish and using zebrafish heart development to study basic fundamental aspects that are conserved between species, such as left-right patterning and the heart.In addition, microscopy and computing are particular interests. We have extensively used 3D reconstruction software in our studies and have developed our own sheet light microscopy System and 3D printer within the group.
I am now starting a major project to apply our knowledge of developmental biology of the heart to human congenital heart disease. Initially I am investigating Hypoplastic Left Heart Syndrome (HLHS), a rare abnormality in which there is severe underdevelopment of the main heart chamber and artery that pump blood out to the body. In these studies I am working with paediatric cardiologists both in Newcastle and Paris and also with the Paediatric Cardiothoracic Surgical Team at Birmingham Children’s Hospital. The initial goal is to understand what are the specific developmental problems underlying HLHS and then to apply developmental experience to identify causative genes in families with HLHS.
Deborah Henderson BSc PhD, Professor of Cardiac Development
Robert Anderson BSc, MD, FRCPath, FESC, FECTS, Visiting Professor
Lorraine Eley, BHF Senior Research Associate
Rachel Richardson, BHF Senior Research Associate
Lindsay Murphy, BHF Research Assistant
Natasha Curley, PhD student
Ahlam Alqahtani, PhD Student