Recent efforts to develop therapeutic strategies for the treatment of some forms of muscular dystrophy have focused on various approaches to allow for read-through of premature stop codons and similar variations that alter the expression of genes relating to muscular dystrophy. These approaches attempt to avoid the effects of a single nucleotide in the DNA sequence that encodes for a protein. Presence of this non-sense mutation may completely disrupt the reading frame of the protein and produce an incomplete, non-functional truncated protein.
We have been engaged for last several years in exploring and understanding how loss of protein(s) leads to loss of adipose tissue, both in animal models and in humans and have developed tools to explore the biology of fat in tissues like the liver and muscle. From this perspective, we have designed experiments to determine why a few muscles, like psoas, in dysferlin-deficient mice, accumulate lipids and to measure the deleterious effect of lipid accumulation in muscle function.
Assistant Professor of Neurology,
Director, UT Medicine Neurology Clinic,
University of Texas health Science Center at San Antonio,
8300 Floyd Curl Drive, MC 7883
San Antonio, TX 78229
We have recently made progress in using 3D cell culture techniques to engineer functional skeletal muscle tissues from human pluripotent stem cells. We will further optimize this technology and apply it to generate contractile muscle tissues using induced pluripotent stem cells (iPSCs) from three LGMD2B patients and two healthy human donors. The resulting iPSC-derived dysferlin-deficient human muscle tissues will be systematically characterized by various structural, functional, and molecular assays.
Our research is focuses on the role of dysferlin in resealing of the skeletal muscle sarcolemmal membrane after that membrane is disrupted.