We develop and use a variety of functional genetic approaches to gain deep mechanistic understanding into the processes controlling muscle development, regeneration, and disease.
Over 800 genetic diseases are associated with defects in skeletal muscle function. Many of these myogenic diseases are diagnosed at birth, arguing developmental defects are major contributors to clinical phenotypes. However, myogenesis is surprisingly understudied and the root mechanisms that underlie a vast majority of myogenic disease are unknown. We see a great opportunity in using forward and reverse genetic approaches in vivo to uncover new genes and mechanisms that govern muscle development and in turn muscle disease.
The novel kinase Bsd regulates myogenesis
FGF signaling directs myotube guidance
Skeletal muscle is one of the most regenerative organs in vertebrates. Amazingly, the stem cells that drive skeletal muscle regeneration were first identified in the early 1960s. Since the advent of modern molecular biology, muscle stem cells have been intensively studied in mammals. Since mammalian systems aren’t amenable to in vivo genetic screens, we have embarked on a forward genetic screen in zebrafish. Our approach is the first to use system-wide muscle injury to identify new genes and perhaps new cell types that drive muscle regeneration. We are also analyzing single cell RNA sequencing of injured zebrafish to identify new candidate genes and cell populations that promote muscle regeneration.
We are collaborating with clinicians at Washington University to identify new genes and variants associated with inherited diseases. One focus of the lab is characterizing muscle diseases known as myopathies using zebrafish. Our in vivo approach allows us to understand how all parts of the musculoskeletal system are affected by and contribute to muscle disease. A second focus of the lab is to use Drosophila as a primary screening platform to understand if gene and variants identified in local patients are causative of a wide array of conditions including structural birth defects and neurological diseases. Our screening approach is aimed at assisting with the clinical diagnosis of patients with genetic disease.