Grant: Project Grant

This research project that uses genetic mouse models to understand how epigenetic enzymes regulate the decision made by muscle stem cells to either maintain their status as a stem cell, or convert into a muscle cell to repair a damaged muscle fibre. We have characterized a pair of mutations in mice where the loss of the protein function prevents the mouse's ability to regenerate its damaged muscle. Importantly, both these proteins required for muscle regeneration are epigenetic enzymes that are proposed to play a role in deciding which identity the cell will take on (ie. remain a stem cell or become a muscle cell that repairs the damaged fibre). Here we will focus on one of these enzymes which talks with cells from the immune system to prevent inflammation from dominating the injured muscle, as this inflammation would prevent the stem cell from efficiently repairing the muscle. We are building on this observation to identify the mechanisms that prevent stem cells from regenerating muscle in conditions of chronic inflammation - a condition we see in many muscle disease as well as in aging. Furthermore we are examining whether drugs that inhibit the function of these enzymes can help improve regeneration in conditions of inflammation. Thus, the knowledge gained from these studies will be important to the development of new therapies to treat muscle degeneration in aging and disease.