The Skeletal Muscle Wasting and Progenitor Cell Biology Laboratory studies skeletal muscle regeneration, muscle-wasting disorders, and stem cell activation and differentiation. The lab is working to improve clinical muscle wasting interventions for patients who experience a decline in skeletal muscle mass or function.
How satellite cells contribute to skeletal muscle repair and regeneration in health and disease is examined in the lab. In addition, Dr. Doles' team is interested in metabolic differences between various forms of muscular dystrophy.
Skeletal muscle wasting
Cancer cachexia is a wasting disease associated with a decline in skeletal muscle mass and function. Approximately 60% to 80% of people with advanced cancer exhibit this comorbidity that is linked to increased mortality, disease morbidity, chemotherapeutic and surgical outcome, and quality of life. Researchers in the Skeletal Muscle Wasting and Progenitor Cell Biology Lab study how tumors (pancreatic and lung) disrupt organismal homeostasis to promote muscle wasting.
Ongoing projects include studies to identify:
- Tumor-derived cytokines and metabolites
- Immune cell contributions to regeneration defects
- The muscle stem cell or satellite cell response to cachectic factors
The focus of research in Dr. Doles' lab is on fully understanding these fundamental mechanisms of cachexia progression to improve clinical muscle wasting interventions.
Satellite cell biology
Satellite cells (SCs) are skeletal muscle resident adult stem cells required for muscle repair and regeneration. In uninjured muscle, SCs typically exist in a quiescent state until called upon to participate in tissue maintenance or repair. Upon exiting quiescence, SCs undergo substantial changes in gene expression, protein homeostasis and metabolic regulation.
Research in Dr. Doles' Skeletal Muscle Wasting and Progenitor Cell Biology Lab investigates myogenic cell state transitions, with a focus on metabolic changes accompanying SC activation. Ongoing projects include single-cell gene expression studies, metabolic profiling of differentiating SCs, and examination of SC defects in the context of metabolic disorders.
Many muscular dystrophy subtypes are associated with systemic metabolic dysfunction. Dr. Doles' research team is interested in how skeletal muscle dysfunction contributes to altered homeostasis in nonmuscle tissues such as liver and fat. Ongoing projects include studies of adipocyte precursor cells derived from murine Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD) models as well as metabolic characterization of the dystrophic SC niche.