Muscle Stem Cells are the Cellular Engines of Muscle Repair
Muscle stem cells are the building blocks for making new skeletal muscle throughout the life of an organism. While adult muscle stem cells are typically quiescent (non-dividing) in uninjured muscle tissue, they are turned on (activated) by local damage where they migrate, multiply, and then differentiate to repair destroyed myofibers. Importantly, muscle stem cells also self-renew to ensure that a subset of the stem cells return to dormancy and are able to engage in future rounds of regeneration.
The “Big” Problem:
The transition from quiescence (i.e., dormancy) to the fully activated stem cell state is the crucial barrier that limits the effectiveness of long-lasting muscle repair. Additionally, defects in muscle stem cell activation substantially contribute to the decline in muscle mass (sarcopenia) and regenerative ability in the growing elderly population and in patients suffering from some of the most lethal and currently incurable muscular diseases, including Duchenne Muscular Dystrophy (DMD). On the other hand, uncontrolled muscle stem cell activation is linked with a family of childhood muscle cancers known as Rhabdomyosarcomas. Although muscle stem cells have been studied for over 60+ years, the early molecular events that transform quiescent stem cells into activated and highly regenerative stem cells in response to stress and muscle damage still remains a virtual “black box”.
Solution:
The Almada laboratory is filling this gap by investigating the mechanics of adult muscle stem cell activation in several vertebrate species (salamanders, lizards, mice, and humans) in order to facilitate the therapeutic preservation of muscle function in vulnerable human populations.
Our research program is divided into three major areas:
- Mechanics of Muscle Stem Cell Activation and Regeneration (Basic Science)
- Mis-regulation of Muscle Stem Cell Activation in the context of Aging and Disease (Translationally-Oriented Basic Science)
- Small-Molecule and/or Stem Cell-Based Treatments for Therapeutic Muscle Repair (Pre-clinical/Translational)
Who are we:
We are a multidisciplinary group of scientists who integrate principals from basic gene regulation, stem cell biology, and translational medicine. We use innovative ‘omic (transcriptomic, epigenomic, and proteomic) technologies and bioinformatic analysis to generate a hypothesis that we can experimentally test using ex vivo (2D culture systems and 3D organoids) and in vivo animal models.
We also closely collaborate with orthopaedic surgeons at the Keck School of Medicine (KSOM) to ensure that our research efforts are aligned with solving real clinical problems.
