Structure and Function of the Domains of Human Dysferlin

To study the structure of dysferlin.

Dysferlin is a large protein with several tandem protein domains of unknown structure and function.  However, mutations in these domains have been linked to LGMD.  The identifiable domains include seven C2 domains, a FerA domain, and DysF.  This project examined the structure and function of the C2 domains as well as the internal domains of dysferlin, FerA and DysF.


Analyzing the Role of Dysferlin in Skeletal Muscle in Vitro and in Vivo

Assess the role of dysferlin in skeletal muscles in vitro and in vivo

We have been studying Ca++ signaling in myofibers in culture that are wild type or dysferlin-null, or that express pathogenic mutants of dysferlin introduced by electroporation.  We have also been examining the effects on Ca signaling of different drugs that target the L-type Ca channels and ryanodine receptors of skeletal muscle.   Our experiments should reveal how dysferlin promotes protection against the loss of Ca signaling following injury, as well as how it can promote subsequent repair, and how drugs targeting the calcium channel proteins of the triad junction can help prevent damage


Quantitation of Proteins Associated with Structural Abnormalities in Dysferlin-Deficient Skeletal Muscle

To evaluate the hypothesis that dysferlin protein organizes or stabilizes muscle fiber structural organization.

Dysferlin deficiency syndromes (dysferlinopathies) are late-onset muscular dystrophies characterized by muscle fiber regeneration, infiltration of inflammatory cells and muscle replacement by fatty tissue. Despite intense study, the molecular basis of dysferlin-deficiency disease remains uncertain. We think that dysferlinopathies may be developmental disorders, due the lack of dysferlin protein in development. The dysferlin protein (230 kDa) interacts (directly or indirectly) with many skeletal muscle proteins and may help to organize or stabilize fiber structural organization.


PPMD Annual Connect Conference

June 26-30, 2016 - PPMD Annual Connect Conference in Washington, DC, USA

The Connect Conference is the largest, most comprehensive annual, international conference focused entirely on Duchenne. It presents an opportunity for families, physicians, researchers, and experts of all kind, to speak face-to-face about Duchenne. These meetings open communication channels, lay the groundwork for future collaborations, and shape our understanding of the Duchenne landscape.

MDA 2015 Scientific Conference

March 11-14, 2015- MDA Annual Scientific Conference in Washington, D.C., USA

The Muscular Dystrophy Association MDA is committed to enhancing the communication of new research findings and of information relating to the delivery of effective medical care for neuromuscular diseases. To achieve this goal, MDA hosts an annual conference series, with scientific and clinical conferences held in alternate years.  

Jain Foundation Attendees: Brad Williams

What is Stem Cell Therapy and can it be used to treat LGMD2B?

Stem cell therapy has been mentioned as a therapeutic option for a diverse group of diseases such as cancer, Parkinson, and muscular dystrophy.  Stem cell therapy involves introducing stem cells into patients to replace damaged tissues.  There are two main kinds of stem cells: embryonic and adult.  Embryonic stem cells are only found in developing embryos and these cells can develop into any cell type in the human body.

What is Exon Skipping and can it be used to treat LGMD2B?

Genes are the instructions manuals that tell the cell how to make the proteins that are needed for the cell to function properly.   When there is an error in those instructions (i.e. a mutation in the gene), the cell is unable to make its corresponding product (i.e. the protein) and this results in a disease.    If the part of the gene containing the error can be skipped, a slightly smaller but potentially functional protein could be made.

What is Gene Therapy and can it be used to treat LGMD2B?

Gene therapy is a therapeutic technique for genetic diseases, such as muscular dystrophies, that involves the injection of a patient with a gene carrier called a “vector.” The vector delivers to the patients’ cells a normal copy of the mutated gene to replace the protein whose absence causes the disease.    Gene therapy is a very attractive therapeutic possibility for the treatment of dysferlinopathy (i.e.