Vascular diseases are leading causes of mortality and disability in developed countries. Blood vessels transcend all organ systems and underlie the crux of many diseases. Our research aims to understand biological mechanisms of endothelial dysfunctions in vascular abnormalities caused by degenerative and inflammatory conditions. 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
Using induced pluripotent stem cell (iPSC) technology, we have invented methods to derive endothelial cells and vascular smooth muscle cells. These iPSC-based vascular models are amenable to gene editing, facilitating mechanistic studies of vascular pathologies. We also harness the replicative potential of human blood outgrowth endothelial cells to recapitulate the biochemical and phenotypic variations conferred by the inflammatory and degenerative disease conditions. Such patient-derived cells enable complex reconstruction of tissues with more physiological relevance for experimentations.
Molecular Underpinning of Endothelial Dysfunctions
Human-relevant vascular models have enabled us to carry out far-reaching experimental strategies. We perform advanced single-cell analysis to discover the diverse cell states adopted by endothelial cells under disease-associated stress paradigms. This allows us to elucidate how molecular mediators regulate cellular heterogeneity, as well as their functional impacts on endothelial barrier function and heterotypic interactions with other cell types, e.g., distinct immune subsets. Our cellular assays can also facilitate drug testing for the development of vascular-protective therapeutics.
Blood borne cells such as circulating endothelial cells and progenitors show characteristic changes in their gene expressions and phenotypes in response to vascular injury. We are developing cell-based biomarkers to predict risk of vascular complications, therefore improving diagnostics for early intervention.