Melissa J. Spencer, Ph.D.

Spencer studies the pathways responsible for muscle health and seeks to understand the pathogenic mechanisms that occur in various muscular diseases. Much of her research focuses on Duchenne muscular dystrophy, the most common fatal childhood genetic disease. Duchenne mutations cause abnormally low production of the dystrophin protein, leading to progressive muscle degeneration and weakness.

In collaboration with center member April Pyle, Ph.D., Spencer is currently developing gene therapy approaches that leverage modified viruses such as adeno-associated viral, or AAV, vectors to efficiently deliver nucleic acids to all muscles of the body. She is also working to improve the efficacy of these therapeutic strategies through capsid engineering, which helps enhance on-target gene delivery and reduce off-target gene delivery. 

To advance the development of these AAV gene therapies, Spencer is devising methods to address their limitations: AAV-based therapies induce an immune response against the viral vector and thus are limited to single dosing. She is studying the interactions between the immune system and AAV to overcome immune reactions, avoid unwanted side effects and enable the possibility of re-dosing. Working in human tissue and mouse models, Spencer seeks to identify targets to suppress the immune system's response to AAV. In addition, she explores how fibrosis in the muscle negatively influences AAV delivery.