|
|
|
APPROACH
|
We apply mass spectrometry and biochemical approaches to understand how metabolites regulate cellular function in pre-clinical models of health and disease.
Our goal is to leverage these newfound mechanisms to develop new therapeutic strategies for metabolic, inflammatory, and metastatic diseases. |
|
Mammalian tissues engage in specialized physiology that is regulated through reversible modification of protein cysteine residues by reactive oxygen species (ROS). ROS regulate a myriad of biological processes, but the protein targets of ROS modification that drive tissue-specific physiology in vivo are largely unknown. We develop technologies for comprehensive understanding of mechanisms of protein redox regulation in physiology and disease.
|
|
MANIPULATING FAT FUNCTION |
Obesity is a global epidemic fuelled 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 signalling mechanisms that define the anti-obesity and anti-diabetic actions of thermogenic adipose tissue. In particular, we identified a key 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 novel 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 IR injury. |