Grant: CIHR REDI Early Career Transition Award - Rare Diseases

The Nuclear Factor-kB (NF-kB) pathways form a signaling complex that is critical for normal skeletal muscle function and is important in promoting recovery in response to muscle injury. It can be divided into two pathways: the classical and the alternative pathway. There is strong evidence that too much classical NF-kB activity is detrimental to normal skeletal muscle function and can contribute to diseases such as the genetic disorder, Duchenne muscular dystrophy (DMD). As such, NF-kB has become an attractive drug target for the treatment of muscle diseases. Unfortunately, none of these drugs are currently being used to specifically treat DMD, likely because we don't know the function of the alternative pathway and how it interacts with the classical pathway in muscle regeneration and disease. Thus, we will use cell culture methods and mouse models to investigate how the loss of alternative NF-kB signaling affects muscle regeneration. We will also examine what it does in a disease context by removing components of the alternative NF-kB pathway in the mdx mouse, the mouse model of DMD. Understanding how alternative NF-kB signaling controls muscle regeneration will allow for a more informed design for the treatment of debilitating muscle diseases such as DMD. Our findings have the potential to improve muscle structure and function and thus the quality of life of patients living with DMD.