Postnatal growth and repair of skeletal muscle requires adult muscle stem cells known as satellite cells. Located between the myofiber plasma membrane and the basal lamina, satellite cells are generally maintained as a mitotically quiescent population until stimulated to activate and exit quiescence. Jason D. Doles, Ph.D., and colleagues study the satellite cell quiescence-to-activation switch, and particularly, how post-transcriptional gene regulation influences this process. Additional work in the lab addresses how satellite cell dysfunction contributes to diverse muscle pathologies including sarcoma and certain muscular dystrophies, as well as age-associated muscle atrophy (sarcopenia).
- Sarcoma. Dr. Doles studies how RNA stability impacts sarcoma initiation, homeostasis and therapy response.
- Muscular dystrophy. Defects in RNA and protein homeostasis underline many forms of muscular dystrophy. Dr. Doles is interested in how inappropriate RNA and protein aggregation contribute to disease etiology.
- Muscle wasting. Dr. Doles and colleagues aim to understand the molecular basis of age- and disease-associated muscle wasting.
Significance to patient care
Current clinical interventions for muscle disease and wasting are inadequate. Dr. Doles believes that a better understanding of muscle stem cell behavior and function will lead to novel and innovative therapies that will improve patient quality of life by precisely controlling muscle growth and regression.
- Recipient, Pathway to Independence Award (K99/R00), National Institutes of Health, 2015-2020
- Long-term fellow, European Molecular Biology Organization, 2011-2013