Metabolism

Inflammation helps to body to fight off infections. However, diabetes can lead to chronic long-term inflammation that may reduce the effectiveness of insulin to reduce blood glucose and inflammation may cause damage to organs like the kidney. Inappropriate activation of innate immune cells such as monocytes and macrophages are involved in this chronic inflammation. This project uses rodent and cellular models to characterize the relationships between immune cell metabolism and metabolic disease and will explore treatments that could restore health by targeting immune-metabolic pathways.

Mitochondria are like engines that use glucose and fats to power the cell. But when this engine runs inefficiently it produces reactive oxygen species which are molecules that can damage cells and tissues.  We have observed mitochondrial dysfunction in type 2 diabetes. This research utilizes a combination of unique tissue restricted experimental animal models, in vivo imaging as well as cellular molecular, proteomic, metabolomic and biochemical, approaches, including the Seahorse respirometer to expand the knowledge about how mitochondrial dysfunction is involved in obesity, diabetes and heart disease. Translational research is achieved through collaboration with the iCARE study. This knowledge aims to guide the development of novel therapies for diabetes and its cardiovascular complications.

Extracellular vesicles are a diverse group of small, membrane enclosed particles that are released by cells into their extracellular environment. These vesicles play important roles in intracellular communication as they can transport biological molecules to transfer information between cells. This research characterizes extracellular vesicle size and cargo and uses in vitro cellular cross-talk models to assess the effects of extracellular vesicles on mitochondrial biogenesis and function. To derive insight into the role of extracellular vesicles in metabolism, transgenic mouse models are used to investigate the effect of exercise and obesity on extracellular vesicles and mitochondria in tandem with studies of exercise in youth with obesity (EXIT trial).

Individuals with obesity and type 2 diabetes are at much higher risk of heart failure. Accumulation of fat leads to impaired heart function and eventually a loss of heart cells through cell death pathways. Once heart cells are lost, they cannot be adequately regenerated. This project studies the regulation of a death gene, called Nix, which is a novel regulator of metabolism and cell death in heart cells. This project uses sophisticated cellular imaging techniques and a unique mouse model of Nix deficiency to understand whether inhibition of Nix and cell death could serve to prevent diabetic cardiomyopathy.

Novel nutritional approaches are essential to combat the rise in diabetes. Functional foods have a health-promoting or disease preventing property beyond supplying nutrients. This translational research integrates animal models with human trials and uses sophisticated mass spectrometry and nuclear magnetic resonance-based metabolomic analyses to identify bioactive molecules in foods and determine the effects that bioactive compounds have on the body.