Cardiac Development and Regeneration
Research on normal heart development, mechanisms underlying congenital heart disease and the potential for applying developmental processes to adult cardiovascular repair.
Congenital heart disease (CHD) is the most prevalent human birth defect, accounting for 10% of all spontaneous abortions and affecting approximately 1% of all live births. Insight into the molecular and cellular mechanisms that underpin the formation of the heart, and associated vasculature, is essential to our understanding of cardiovascular birth defects. Moreover, the same principles that are employed to orchestrate normal development during pregnancy can equally be harnessed to design regenerative strategies to treat both congenital and adult-onset disease. Cardiovascular disease (CVD) leading to acute myocardial infarction (MI; “heart attack”) affects around 230,000 people each year in the UK, resulting in an annual death toll of approximately 90,000 (www.heartstats.org). Whilst the number of deaths is falling, improvements in treatment for MI, alongside an ageing population, have resulted in a significant increase in people living with heart failure. Heart failure remains the major cause of morbidity and mortality in humans and is a growing global health problem. Corrective surgery for CHD and heart transplantation in adult CVD remain the only viable cures.
The principle research goals of the Cardiac Development and Regeneration (D&R) theme are to:
- improve the current understanding of the molecular and cellular inputs that control normal cardiovascular development
- decipher the mechanisms that cause CHD and an increased susceptibility for acquired CVD
- identify developmental gene programmes and embryonic cell potential as targets for reactivation in adult cardiovascular tissues following disease or injury
- establish novel therapeutic strategies designed to regenerate, repair and replace affected tissues
The direct application of developmental biology to regenerative medicine is a major strategic goal across the CRE and is underpinned by the virtual BHF Oxbridge Centre for Regenerative Medicine.
The D&R theme incorporates active research programmes in developmental biology that extend across multiple animal model systems (mouse, chick, Xenopus, zebrafish, Medaka and the Mexican Cavefish) and extrapolate to human CHD and human iPSC models of CVD. Research synergy exists via neighbouring CRE themes in Vascular Biology and Myocardial Biology, underpinned by investigators from DPAG, the Dunn School of Pathology, the WIMM and Department of Cardiovascular Medicine. Specific expertise exists in embryology, stem cell biology, cellular reprogramming, disease modelling, transcription factor signalling, gene targeting and editing and high resolution live imaging. Genomics and epigenetics, combined with statistical and mathematical modeling, systems biology and bioinformatics are incorporated via the Genetics & Inherited Diseases theme, to establish clinical evidence for genes and pathways that determine CHD. Partnerships with the Target Discovery theme seek to devise efficient pharmacological approaches to control cardiovascular cell differentiation and function, to probe pathways for novel cardiac developmental and disease candidate genes and to target disease progression, drug screening and treatment.