Pursuing New Treatments for Muscular Dystrophy and Heart Disease
The Maves lab uses zebrafish to study why certain muscle fibers are susceptible to muscular dystrophy.
The Maves lab has shown that Pbx and Meis homeodomain transcription factors are required for both skeletal muscle differentiation and heart muscle differentiation. The lab is currently trying to understand how Pbx and Meis factors influence muscle differentiation in the contexts of muscular dystrophy and congenital heart disease.
Making Muscles Less Vulnerable to Muscular Dystrophy
Early slow-twitch (red) and fast-twitch (green) muscle cells in a zebrafish embryo.
The Maves lab is illuminating the mechanisms that let muscular dystrophies impair muscle cells, and investigating new therapies that could limit the disease’s effects.
Certain muscular dystrophies preferentially affect fast-twitch or slow-twitch muscle fibers. The Maves lab uses zebrafish and mice to investigate how particular genes control whether muscle fibers become fast-twitch or slow-twitch. This work lays the foundation for identifying therapies that could alter muscle fiber type and help muscle cells resist muscular dystrophy.
Pinpointing How Genes Influence Muscle Cell Differentiation
High-magnification image of muscle fibers in a zebrafish larva.
The lab is making key discoveries about how genes influence the way muscle cells form. Maves and her colleagues recently found that Pbx genes act in conjunction with the Prdm1a gene to regulate whether cells can differentiate into fast-twitch muscle cells. These findings pave the way for identifying how muscle cell differentiation is controlled.
Identifying How Genes Help the Heart Form
The Maves lab collaborates with Dr. Mark Majesky on the Seattle Children’s Myocardial Regeneration Initiative, which investigates how different types of heart muscle form, laying the foundation for stem cell therapies that repair congenital heart problems.
The lab is unraveling how different genes guide heart formation. For instance, in a recent paper, Maves and her colleagues showed that the gene Meis2 ensures that the heart tube – the initial structure that develops into the heart – forms properly in zebrafish. Understanding the role of this and other genes helps answer longstanding question about how the heart develops. This provides vital knowledge that will help researchers learn how to step in and correct heart development when it goes awry.
Editing the Genes That Cause Heart Defects
The lab is using TALEN enzymes to engineer mutations in zebrafish Meis and Pbx genes, with a goal of understanding how mutations in these genes lead to heart defects. Testing these gene functions in animal models propels Maves and her colleagues toward a future where they could correct the genes that cause heart defects in humans.