Project 458950

Adolescent idiopathic scoliosis (AIS) is a debilitating disorder characterized by complex three-dimensional spinal curvatures that affect ~ 4% of the population worldwide. AIS arises during adolescence and if severe can cause functional disability, disfigurement, social anxiety, and chronic pain. While rigorous research has been conducted on AIS over the past few years, the underlying biological causes of AIS are still poorly understood. Thus, only antiquated treatment options for AIS exist, such as bracing and/or invasive surgery. To understand the causes of AIS and discover more effective non-invasive treatments, our research group pioneered the use of zebrafish as a model for AIS. Zebrafish are naturally susceptible to spinal curvatures and are believed to experience similar forces as humans on their spine from swimming. Remarkably, the zebrafish models develop similar three-dimensional spinal curvatures as seen in human AIS. We have discovered that a lack of cerebrospinal fluid flow, and downstream oxidative stress and neuroinflammation can cause AIS. However, the exact biological mechanisms and pathways driving curve formation remain unknown. With the help of our zebrafish models, drug library screens, genetic manipulation, as well as molecular and biochemical approaches, I aim to uncover the pathways and tissues responsible for the disease progression. My research will help define what is occurring in this complex disease and provide new insights for non-invasive therapies in hopes to treat human patients with AIS.