Progress Update: Regulation and activity of the DUX4 transcription factor

Submitted by Dr. Stephen Tapscott

See Grant Regulation and activity of the DUX4 transcription factor

Note that the Chris Carrino Foundation shares in funding this multi-year grant.

This award supports several areas of FSHD research. It supports studies of muscle biopsies from FSHD individuals that identify the gene expression signatures that distinguish FSHD muscle from unaffected muscle. These studies are leading to a better understanding of why the muscles might function relatively normally in early life and then loose strength at later times. Not only will this help to plan clinical trials for FSHD, but it also will inform treatment strategies for preventing the progression of muscle weakness. The award also supports research to determine where DUX4 is normally expressed. This study uses a mouse model with a reporter gene that will mark cells expressing the mouse version of DUX4. After determining where the mouse version of DUX4 is expressed, we can then look at human tissues for similar expression of the human DUX4. The final project focuses on a set of proteins that disappear when DUX4 is expressed. These proteins normally regulate how the immune system is activated and we want to know whether the loss of these proteins contributes to the disease progression in FSHD, which would potentially be a new target for developing drugs to treat FSHD. Funding from the foundations contributed to seven publications during the last two years.