vCardDr Simon Bamforth

Dr Simon Bamforth
BHF Intermediate Research Fellow

  • Email: simon.bamforth@ncl.ac.uk
  • Telephone: 0191 241 8764
  • Address: Institute of Human Genetics
    Newcastle University
    International Centre for Life
    Central Parkway
    Newcastle upon Tyne
    NE1 3BZ

Research Interests

Genetics of cardiovascular development

Congenital cardiovascular malformations are among the most common birth defects, occurring in up to 1% of live births, and affect the outflow tract of the heart and the great vessels that arise from it. The aorta and pulmonary trunk emerge from the left and right ventricles respectively and connect to the pulmonary, carotid and subclavian arteries that supply blood to the lungs and the rest of the body.heart These blood vessels are derived from the pharyngeal arch arteries and develop during embryogenesis from a bilaterally symmetrical structure to a highly asymmetrical one through a complex remodelling process involving apoptosis and blood flow. When this developmental process goes awry, patients suffer from cardiovascular conditions such as Tetralogy of Fallot, common arterial trunk, transposition of the great arteries, interrupted aortic arch and anomalous right subclavian artery. In patients, some of these defects can be attributed to syndromes or chromosomal abnormalities, but the majority occur through an unknown genetic component.

My research group is investigating how certain genes, expressed within the developing pharyngeal arches, can control the correct development of the heart and its associated great vessels using transgenic mouse models, imaging techniques and gene expression patterns. Gene mutations in mouse models can be very informative in understanding how a gene controls certain developmental processes. However, many of these mouse models are early embryonic lethal, or have complex phenotypes due to multiple developmental pathways. Consequently, dissecting the role of a single gene in a particular tissue is extremely difficult. This problem can be overcome by specifically deleting the gene in a tissue-restricted manner using the Cre/LoxP system in transgenic mice.

Mice mutated for the transcription factor AP-2a have, amongst other developmental defects, cardiovascular malformations and die around the time of birth.3D AnalysisAs AP-2a is widely expressed during development we are deleting it from specific tissues to identify where AP-2a is required for correct development of the outflow tract and pharyngeal arch arteries. To look for early changes in pharyngeal arch artery patterning we are examining mid-gestation embryos by optical projection tomography. To identify cardiovascular malformations at a late stage of gestation in the developing embryo, we are screening them using magnetic resonance imaging. This is a particularly powerful technique for rapid 3D analysis of complex cardiac malformations. We hope that this research will identify where AP-2a is required to control the normal formation of the outflow tract and pharyngeal arch arteries during development. These studies will result in mechanistic insight into how cardiovascular developmental disorders in humans may occur.

Co-Workers

Divya Venkatesh MRes
Research Assistant
Amy-Leigh Johnson
Newcastle University
PhD Student

Selected Publications