Five Questions with DMD Researcher James Ervasti

James Ervasti, PhD, professor of Biochemistry, Molecular Biology, and Biophysics at the University of Minnesota, Twin Cities, was awarded an MDA research grant totaling $300,000 over three years to study the mechanical characterization of dystrophin in Duchenne muscular dystrophy (DMD). DMD is caused by a mutation in the dystrophin gene on the X chromosome that results in little or no production of dystrophin, a protein that is essential for keeping muscle cells intact. Dr. Ervasti will test the hypothesis that dystrophin and utrophin act as shock absorbers by mechanically characterizing both proteins, with the aim of informing development of dystrophin gene-targeted therapies and other drugs (including utrophin-promoting drugs) that might be used to replace the function of dystrophin in DMD. Please describe your current research. Dystrophin is widely believed to provide mechanical support for the muscle plasma membrane, but there is little known about its mechanical properties. What is the focus of your research in DMD, and why is it important? A major focus of my research is on the structure and function of dystrophin and utrophin. We still don’t fully understand what dystrophin does to keep muscle healthy and whether utrophin can do everything that dystrophin can do. What inspired you to study DMD? Muscle biology and disease became my research passion while studying the muscle disease malignant hyperthermia for my PhD thesis. Dr. Kevin Campbell invited me to join his laboratory in 1989 and provided me with a dream project to identify the glycoprotein that anchors dystrophin to the muscle plasma membrane. I’ve been studying dystrophin ever since and continue to be inspired by all the patients and families that I have met over the last 30 years. What is the expected outcome of your research? We expect to define the mechanical properties of dystrophin. How will your research lead to treatments and cures? Our work will inform on how similar or different dystrophin is from utrophin in terms of mechanical function. Why is it important that MDA continue to fund research in DMD? While there has been tremendous progress in the advancement of therapies to treat DMD patients, we still have not cured anyone of the disease, and I believe that a better understanding of the problem will lead to better solutions.