Principal
Investigator: Jeffery Chamberlain
Co-Investigator: Stan Riddell, Leo Wang, Rabi Tawil, Seth Friedman, Stephen Tapscott, Dennis Shaw, Sandy Poliachik and Michelle Schaffer
This project relates to the broad scope of the Center because it develops the clinical infrastructure necessary
for future gene therapy trials in Duchenne and FSHD dystrophies at the University of Washington, and for
future inter-institutional trials in muscular dystrophies. In addition it provides a rich translational clinical
research program for the Investigator Development and Patient Outreach Core and it uses vectors produced
by the Scientific Research Resource Core.
One of the aims of this project is a cooperative clinical study for biomarker evaluation in FSHD that will develop FSHD
patient registration, assessments, and sample collection in Seattle that parallel those developed in
Rochester; develop FSHD MRI assessment capabilities in Rochester that parallel those developed in
Seattle; and perform a focused collaborative clinical study to determine the molecular determinants of the
MRI findings characteristic of FSHD and to prioritize the best candidate biomarkers for disease activity.
Additonally we are working to determine whether CD8+ T cells infiltrating FSHD muscle recognize DUX4 induced cancer/testes (C/T)
antigens, and to characterize the phenotype, location, and cytokine profile of the T cell/immune cell
infiltrate in skeletal muscle in FSHD. We are also doing research which will expand T cells from FSHD muscle, determine the T cell receptor Vb
gene usage and characterize their function; and determine whether T cells derived from FSHD muscle
recognize FSHD muscle antigens. These combined studies represent a synergistic effort to evaluate the
relationship between tissue biomarkers, histopathology, MRI imaging characteristics, and muscle function,
together with a direct characterization of the T cell infiltrate the immune response in the pathophysiology of
FSHD. |