The saying goes 'A man is as old as his arteries'. Blood vessels transcend all organ systems and underlie the crux of many health conditions. Our research aims to understand biological mechanisms regulating vascular ageing in diseases such as stroke and coronary artery disease. We employ advanced molecular techniques, human-relevant experimental models and patient-derived materials to elucidate pathological endothelial cell behaviours. Our work provide insights for translation to restore blood vessel health and regenerative therapies.
Personalised vascular models
There are well-studied morphological, biochemical and phenotypical heterogeneities in our blood vessel system. Using the human pluripotent stem cell (hPSC) technology, we have invented techniques to derive vascular smooth muscle and endothelial cells, resembling those found in the brain and heart arteries. Such resources open the door to creating personalised vascular models that are amenable to comprehensive phenotypic assessment and gene editing. The hPSC-based vascular models also enables far-reaching experimental strategies e.g. drug/inhibitor screening to facilitate the development of novel therapeutics.
A key challenge of interpreting genetic risk variants from genome wide association studies is that most variants do not encode genes. Emerging evidence suggests that non-coding variants may reside in regulatory elements or influence the activity of other gene-coding regions through long range chromatin interactions. We are working on the genotype-to-phenotype basis of vascular disease-associated variants, in order to elucidate how transcriptional and epigenetic modulators impact on phenotypic differences between normal and diseased cells.
Immune cells and vascular progenitor cells show characteristic changes in their gene expressions and phenotypes in response to vascular injury. We are developing prognostic biomarkers that are well-grounded on the function of these blood-borne cells. Deep-dive analysis of patient-derived cells would reveal mechanistic differences in ‘susceptible’ versus ‘protective’ individuals, improving diagnostics for early intervention.