Juvenile dermatomyositis (JDM) is an autoimmune condition that affects children’s muscles, skin, and other organs like the lungs and the intestines. It can cause weakness and disability, and some patients may experience very severe symptoms that can lead to death. We unfortunately know very little about why JDM develops. From work in other rheumatologic diseases, we have learned how to target the specific pathways that are abnormal in autoimmunity, and this is my hope for the future of JDM treatment, as well. To achieve that goal, however, we need to better understand the types of cells that are involved, how autoantibodies contribute to disease, and biomarkers that can predict how patients will respond to different medications. All of these unanswered questions are addressed in this proposal. In the realm of cancer and precision medicine, model systems including cell cultures and animal models have been used as patient “avatars” to help predict the best treatment options. My proposal will use these types of systems to answer fundamental questions about how myositis develops. These “avatars” may someday be useful in cases of hard-to-treat autoimmune diseases like refractory JDM. For now, though, my hope is that by better understanding what causes JDM, we can start to develop highly targeted treatments with better efficacy and fewer side effects for all of our patients, hopefully preventing the need for more drastic and expensive therapies.