The Singapore epigenome project aims to explore epigenomes of human diseases starting with heart failure and autism spectrum disorder. Heart failure is a major cause of morbidity and mortality across the world, with a predominance that is shifting to Asia, consistent with the burgeoning and ageing population in this half of the world. As the final common pathway for nearly all other cardiovascular diseases, heart failure has a high mortality, in severe cases up to only 50% survival in 5 years. Novel therapeutic options for HF are urgently needed. Emerging evidence suggest that the cardiac epigenome holds clues not only to novel therapies but also to means of stratifying therapies.
On the back of a substantial A*STaR Cardiovascular disease programme, and including intra and extramural funding for the cardiovascular research programme based at the Cardiovascular Research Institute (National University of Singapore) and Genome Institute of Singapore, the Singapore cardiac epigenome programme sets out to map DNA methylation profiles, cardiac chromatin organisation, and interaction between cardiac genes and their regulatory elements. We will be generating methylome and epigenome profiles of 100 healthy and diseased human hearts.
Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder characterized by impairments of social interaction and repetitive behavior. ASD affects over 1% of the population in developed countries, and potentially a similar proportion in other countries as well. There are currently no approved drugs for treating the core symptoms of autism, but improved molecular understanding of the underlying mechanisms could provide clues to the development of new therapies. Though etiologically heterogeneous, some studies have suggested that there could be common epigenomic signatures in ASD that potentially reflect its phenotypic hallmarks. Funded by the NIMH-USA and A*STAR-Singapore, the Singapore ASD epigenomics group, in collaboration with researchers at UCLA and the University of Exeter, is mapping histone acetylation profiles in hundreds of postmortem human brain samples from affected and control individuals. These data will be integrated with transcriptomic and methylomic readouts generated by the collaborating groups to construct an integrative map of molecular aberrations and interactions in ASD brain.
In subsequent years, we aim to enlarge the effort in Singapore to epigenomes for other disease cell types, including potentially hepatocytes of fatty liver, monocytes and granulocytes from patients with diabetes and tuberculosis, solid tumours, aged blood cells and neurons from patients with dementia.
Singapore cardiac epigenome project.
Roger Foo group
Cardiovascular Research Institute
National University of Singapore & Genome Institute of Singapore
Singapore ASD epigenome project.
Shyam Prabhakar group
Genome Institute of Singapore