Obesity promotes diverse pathologies, including atherosclerosis and dementia, that frequently involve vascular defects and endothelial cell (EC) dysfunction. Consistent with their functions, vascular cells in each organ are unique. For instance, vascular cells in the lungs are specialized for gas exchange, kidney endothelial cells to help with filtration of fluids, while neural vascular cells make up the blood-brain-barrier. Whether and how metabolic disease effects these wide-array of blood vessels remains unclear.

Through single cell transcriptomic and epigenetic approaches, we have uncovered extensive heterogeneity and the impact of metabolic disease on vascular cells. Vascular cells across organs are differentially impact by obesity, suggesting that a metabolic imbalance triggers unique organ-specific changes. Importantly, these changes are only partially reversible via weight loss and improved metabolic health, suggesting the presence of an epigenetic memory.

In this project, we aim to understand the physiological consequences of the transcriptional changes triggered by obesity, the epigenetic memory in vascular cells, and the mechanisms responsible for storing epigenetic memories. The ultimate aim of this project is to develop strategies to revert the “high-risk” obesity transcriptome towards a healthier state.