Overview

Our team combines techniques in molecular biology and imaging with mouse models to uncover mechanistic insight into the influence of environmental exposures on cardiometabolic health throughout the lifespan. 

Developmental origins of adipose function: Intrauterine life is a phase of rapid growth and maturation that is highly sensitive to environmental insults.  When adverse intrauterine conditions provoke adaptations in developmental trajectories, this can have a lasting impact on organ function that increases the risk for adult-onset chronic disease. In today's obesogenic environment, metabolic disorders such as maternal obesity and gestational diabetes, have burgeoned into the most common pregnancy conditions. Human studies reveal that babies born from mothers who were obese or diabetic during pregnancy are more likely to develop early onset obesity in childhood and are at higher risk for cardiovascular disease and type 2 diabetes in adulthood. Our work highlights adipose tissue dysfunction as a key factor linking maternal obesity to later-life cardiometabolic disease in the offspring. Our findings suggest that this predisposition to adipose tissue dysfunction stems from an intrauterine perturbation in the establishment of adipose progenitor cells, which program the set point of adiposity in early life and maintain the functional integrity of adipose tissue in adulthood. This insight is critical to design strategies effective in optimizing long-term outcomes in babies born at risk.   

The influence of sex and estrogen on adaptations of adipose tissue: Recent developments in the field of adipose biology have revealed adipose progenitor cells as key players in the ability of adipose tissue to adapt to an obesogenic environment. However, over-reliance on a male model of research has obscured the understanding of sex differences in the risk for obesity-induced type 2 diabetes and the heightened risk for diabetes in post-menopausal women. Our findings demonstrate that protection against obesity-induced diabetes in young females is largely attributable to depot-specific responses of adipose progenitor cells, whereas loss of this plasticity due to a decline in estrogen levels contributes to increased risk for insulin resistance. Our lab is currently probing the role of adipose tissue macrophages in governing the estrogen-dependent behaviour of progenitors in the setting of obesity. 

Sex and estrogen receptor-mediated vascular responses to plastic-derived chemicals: Chemical intensification of our environment is a significant, yet underappreciated, contributor to chronic diseases such as obesity and other cardiometabolic disorders. Currently, we are investigating substitutes used to replace bisphenol A (BPA), a commonly used synthetic chemical present in household products and plastic food and drink containers. A growing body of evidence reveals BPA substitutes as another example of 'regrettable substitutions' where industry replace toxic chemicals with equally toxic substitutes. Our findings show that exposure to BPA substitutes has a sex-dependent impact on vascular function, whereby males are vulnerable to impairments in nitric oxide-mediated vasodilation due to oxidative stress and females are protected. Further, our results suggest that this sexual dimorphism is due to an interaction of bisphenols with estrogen receptor signalling.