Mark Nixon, PhD

Glucocorticoids are critical stress hormones that regulate a number of physiological processes including fuel metabolism and immune modulation. Conditions of overt glucocorticoid excess such as Cushing’s disease or chronic glucocorticoid treatment are associated with significant cardiometabolic abnormalities, including obesity, hyperglycemia, and hypertension.

Indeed, while glucocorticoid treatment is a cornerstone in the management of many inflammatory diseases, and glucocorticoid replacement is essential for survival in patients with various forms of adrenal insufficiency, cardiovascular disease risk is increased 6-fold in people exposed to long-term supraphysiological doses of glucocorticoids. Notably, this association is more pronounced in women, highlighting sexually dimorphic responses to glucocorticoid therapy.

Obesity, as a key driver of cardiovascular risk, is associated with complex glucocorticoid dysregulation, the direction of causality and the pathophysiological consequences of which are unknown. My lab addresses the hypothesis that obesity-induced glucocorticoid dysregulation is a key component in the development of these significant co-morbidities. Similarly, cardiovascular risk is increased in those subjects exposed to glucocorticoid excess.

My lab’s discovery of mechanisms which confer tissue-specific control of glucocorticoid action independently of circulating levels provide the basis for a paradigm shift in the understanding of glucocorticoid biology, and uniquely position us to determine the impact of these mechanisms on co-morbidities associated with obesity, as well as on glucocorticoid-induced cardiovascular risk.