Our research focuses on deciphering the molecular mechanisms of metabolic disease and dysfunction, and using this information to develop targeted therapeutic strategies. Dysfunction in a particular cellular locale – the mitochondrion – is implicated most age-related disease pathology. We apply mass spectrometry, biochemical, and genetic approaches to identify mitochondrial metabolic pathways that control the protective and pathological cascades initiated by this organelle. Our work to date has focused on elucidating these mechanisms of damage and protection in pre-clinical models of cardiovascular and metabolic disease:

Manipulating fat function

Obesity is a global epidemic fueled by ageing populations and poor dietary habits. The health consequences are widespread and escalating, as obesity is a major risk factor for leading causes of death including diabetes, cardiovascular disease, and cancer.

While accumulation of white fat drives obesity, we now know of a second type of healthy “brown” fat that can counteract obesity and diabetes. We hypothesize that if we can understand how metabolic signals control healthy versus unhealthy adipose function, we can manipulate them as a new way of treating metabolic disease. ​

Recently, we uncovered new metabolic signaling mechanisms that define the anti-obesity and anti-diabetic actions of thermogenic adipose tissue. In particular, we newfound role for redox signaling in control of healthy thermogenic brown adipose function.

Protecting the heart

​Cell death and tissue damage due to myocardial infarction (heart attack) underlies this leading cause of mortality. With collaborators, we have focused on unraveling mechanisms of, and targeting therapies against, the metabolic dysfunction that drives injury in myocardial infarction.

We developed in vivo biochemical and proteomic methods to establish the mechanistic basis for cardioprotection by nitric oxide within mitochondria, and developed a long sought-after targeted therapy for treatment of acute myocardial infarction. Following on from this, we developed in vivo metabolomic methods to identify how novel metabolic pathways fuel mitochondrial reactive oxygen species (ROS) production during myocardial infarction.