Grant: Foundation Grant

<html> <body> <p> <b>Direction of Research Program:</b> Mood and anxiety disorders are rapidly becoming one of the largest health burdens in the Western world. Currently, there are no broadly effective treatments for these disorders. Stress has long been recognized as a major precipitating factor in the onset of these diseases, but comorbid anxiety and depression are also highly prevalent in populations afflicted with inflammatory conditions. Understanding the basic neural mechanisms subserving sensitivity to stress and the regulation of mood and anxiety is germane to our ability to manage this growing societal issue. The endocannabinoid (eCB) system has emerged as a major player in the regulation of stress and anxiety, with convergent findings demonstrating the importance of this system in humans and rodents. The overarching <b>direction</b> of my research program is to comprehensively understand the mechanisms by which eCB signaling and stress interact within the brain. In the broader context, my program also explores how this system acts as a general homeostatic signal that influences natural variation in stress and emotionality within a population, and contributes to comorbid changes in stress and anxiety in response to physiological disturbances, such as inflammation. The guiding hypothesis of my research is that the eCB system is an important endogenous modulator of neural activity within corticolimbic circuits regulating stress and emotionality, and that pharmacological enhancement of this system may represent a novel treatment strategy to promote resilience against the manifestation of anxiety and depression.<br> <br> <b>Objective #1</b> will delineate the neurochemical and cellular mechanisms by which stress exposure impacts eCB signaling.<br> <br> <b>Objective #2</b> concentrates on understanding how perturbations in eCB signaling act as a generalized mechanism by which changes in stress sensitivity and anxiety emerge from a variety of physiological conditions, such as inflammation.<br> <br> <b>Objective #3</b> will determine the role of natural variation in eCB signaling in mediating individual differences in stress sensitivity and trait anxiety.<br> <br> These basic science approaches will be translated through my clinical and industry collaborations that focus on the importance of eCB signaling in trait anxiety and susceptibility to psychiatric illnesses in human populations. Given that several clinical studies have indicated that eCB signaling impacts human stress sensitivity and emotional processing in a parallel manner to rodents, my research program is positioned to strongly impact our understanding of human mental health and disease.<br> <br> My research program takes a systems-level approach incorporating a range of techniques spanning molecular biology to behavioral analysis. The basis of this research program is built on the team of phenomenal trainees in my lab, collaborations with skilled and relevant collaborators on site and my broad network of basic and clinic researchers, who provide novel tools and skills to facilitate these studies.<br> <br> My research program will benefit the trainees involved by helping them develop a broad toolkit to approach neuroscience. This includes an understanding of how basic and translational research can be mutually informative and, establishing collaborations to answer key scientific questions. These training activities will be augmented by a first-class professional development platform within the Hotchkiss Brain Institute.</p> </body> </html>