DrWilliam Scott

My research group is focused on understanding the mechanisms that underlie human obesity, type 2 diabetes (T2D) and dementia, global health challenges with limited treatment options. Specific aims are to:

1. Discover, characterise and modify epigenetic mechanisms that cause human obesity and T2D. Contrary to previous human epigenomic studies, our recent work demonstrates that tissue- and cell-specific epigenetic mechanisms are important determinants of human obesity and diabetes. We are currently applying advanced genome editing tools in human cells and disease models to systematically evaluate epigenetic causation and therapeutic potential.

2. Understand how weight loss induces remission of T2D to inform the development of new T2D therapeutics. We are using single cell and spatial genomics in human adipose tissue to reveal cell types and genes that coordinate the beneficial effects of weight-loss on (i) obesity-induced metabolic dysfunction and (ii) T2D remission. In parallel, we are developing experimental and informatic approaches to explore how the adipose tissue secretome (proteins, metabolites, extracellular vesicles) regulates insulin sensitivity and secretion in other metabolic tissues.

3. Identify and target the mechanisms by which blood brain barrier damage causes dementia and ageing. We are using advanced in vivo imaging to measure blood brain barrier leakage and high-throughput molecular screening to delineate pathobiological pathways underlying blood brain barrier dysfunction in mouse models of human dementia and ageing. We are then combining orthogonal genetic, environmental and therapeutic strategies to reverse key pathobiological defects in preclinical disease models.

Ultimately, we aim to define novel therapeutic targets to manipulate to improve the health of people with obesity, diabetes and dementia.