Grant: Foundation Grant

My research program integrates discovery, translational and clinical research with a goal of optimizing fetal health and preventing the negative life-long consequences of early adversity. It is predicted that chronic diseases/disorders will account for 50% of global disease burden by 2030, costing $47 trillion. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) system that regulates cortisol (the primary stress hormone) can drive a number of these chronic disorders. We have determined that adverse fetal environments (including maternal/fetal stress and certain therapeutic drug treatments) can program life-long function of the HPA axis, which can predispose individuals to disease in later life. In related studies, my group discovered that the fetus possesses a sophisticated protection mechanism. We found that transporter proteins (first discovered in cancer cells) are present in the placenta and fetal brain, where they prevent entry of a wide range of substances including maternal stress hormones, anticancer, anti-HIV and pesticides into the fetus and its brain. We also discovered that pregnancy complications (i.e. infection) change levels of these proteins, decreasing fetal protection. Utilizing a multidisciplinary approach, my team will determine the mechanisms by which adverse fetal environments program life-long susceptibility to endocrine (HPA axis) and behavioural disorders; develop tools to help identify individuals at risk; and create interventions that reduce the burden of chronic disease in individuals that experienced early adversity. We will also determine the regulation of the key transporter proteins that protect the fetus in normal and abnormal pregnancies. Harnessing this new knowledge will provide opportunity for innovative new therapeutic approaches for the fetus and mother and improve health in the next generation. During this program, I will train and mentor over 50 undergraduate, graduate students and postdoctoral / clinical fellows