Research Theme: Mammalian development, stem cells, regeneration and disease

Stem cells are specialized cells crucial for embryonic development, adult tissue maintenance and repair, and play vital roles in diseases such as muscular dystrophy and cancer. Using mammalian genetic models, our lab is interested in deciphering the mechanisms underlying four important events and processes that occur during the life span of mammals: 

1. embryonic development, 

2. stem cell-mediated regeneration, 

3. tissue homeostasis, and

4. diseases. 

First, during development, embryonic stem cells undergo a predetermined program of differentiation, controlled by autocrine and paracrine signals. We aim to unravel the mechanisms underlying muscle differentiation, identifying the genes and pathways involved. Second, regeneration of the adult skeletal muscle is primarily carried out by the muscle-resident stem cells known as satellite cells. 

We are studying how the satellite cells remain dormant normally, are activated upon injury and various signals control their function. Third, we are interested in understanding the maintenance of the skeletal muscle, a contractile, highly metabolically active tissue, contributes to overall body homeostasis. Among the signals that regulate muscle homeostasis, we identified one to be mechanical, called mechanotransduction. 

Fourth, stem cell function is associated with numerous diseases and therapies, where we have multiple interests. Cancers such as rhabdomyosarcoma occur due to uncontrolled proliferation of muscle stem cells, where we are identifying the pathways and genes affected, for use as therapeutic targets.

Genetic diseases such as Duchenne Muscular Dystrophy, Spondylocarpotarsal Synostosis, Limb-Girdle Muscular Dystrophy and several more are caused by mutations in specific genes crucial for muscle function. 

We are developing cellular and animal models to understand such diseases, characterize the disease pathology, identify dysregulated molecular pathways and develop therapies, such as using induced pluripotent stem cells (iPSCs).

We are also studying how skeletal muscle dysfunction contributes to neurodegenerative diseases such as Parkinson’s disease and lifestyle diseases such as type 2 diabetes.