What is FSH? >>>

217 19th Place
Kirkland, WA 98033
Tel: 425-827-8954

What is FSH? >>>

Friends of FSH Research
depends on private
donations from individuals
and corporations. Donations are accepted throughout the year as well as at our annual fund raising dinner and auction. To learn more about the "FiSHing for a Cure" auction, visit our AUCTION page

• Our Organization
• Our Mission
• Board of Directors
• Advisory Board
• Measuring Effectiveness
• Current Annual Report
• Current Tax Form 990
• Current Income/Budget

• Overview
• Sponsorship Packages
• Financial Donations
• Volunteer Services
• Auction Items
• Used Items
• Stocks & Securities
• Power of the Pen

• Overview
• Forms & Donations
• Preview Items
• Sponsors & Donors

• Research News
• Funding News
• Researchers
• Grant History
• Request A Grant
• FLEX Fund
• FLEX Scholars
• Links & Resources

Friends of FSH Research Funded Projects in Tapscott Lab at FHCRC

12-jan-2012

Major advances in research over the last two years have determined that FSHD is caused by the aberrant expression of the DUX4 gene in skeletal muscle. DUX4 is normally expressed in germline cells and early development, but tissues in the adult completely suppress the expression of DUX4. In FSHD the suppression is incomplete and DUX4 is expressed in mature skeletal muscle. Recent work in the Tapscott lab has shown that DUX4 normally regulates the expression of germline and stem cell genes and that the mis-expression of DUX4 in skeletal muscle activates that expression of these early developmental genes. Work recently funded by Friends of FSH Research will use these findings to develop the components necessary to identify drugs that prevent the DUX4 expression and/or DUX4-induced damage in muscle cells. The Tapscott lab plans to develop several ways to measure DUX4 expression and toxicity, and then perform tests to see how well each can be used for a large-scale screen of possible drugs. As the tests are validated it is anticipated that pharmaceutical companies might adopt them to screen their extensive libraries of drug-like compounds.

— Stephen Tapscott

The DUX4 protein (green blob) is normally expressed in germ cells and early stem cells (blue circle) where it binds to DNA (horizontal lines) and activates the expression of gametogenic and stem cell genes, as well as a gene called Defensin. As the stem cells differentiate into muscle DUX4 is normally completely turned off and is not present in adult skeletal muscle. In FSHD skeletal muscle (pink blob) DUX4 continues to be expressed and continues to activate the expression of germline and stem cell genes, as well as the Defensin. The germline genes might directly damage the skeletal muscle and also might induce an immune response to skeletal muscle. The Defensin is a protein that both enhances immune responses and blocks muscle regeneration, possibly having two deleterious roles in FSHD.