Dr. Nagaraju’s laboratory is involved in studying the mechanism of muscle fiber damage and dysfunction (weakness) in autoimmune myositis. His laboratory is mainly focused on studying both immune (cell-mediated and humoral) and non-immune (ER stress, autophagy) mechanisms of muscle fiber damage in myositis. Drs. Nagaraju and Plotz generated the first inducible transgenic mouse model of myositis by over-expressing syngenic major histocompatibility complex class I molecule in the skeletal muscle. These transgenic mice expressing transgenic H-2Kb in skeletal muscle develop clinical, biochemical, histological and immunological and phenotypic features similar to human polymyositis. This mouse model is currently being used by several myositis researchers both within and outside United States. Recent data from Dr.Nagaraju’s laboratory demonstrate that non-immune pathways (e.g., ER stress) are highly active within the skeletal muscle of myositis patients, and the pro-inflammatory NF-kB pathway connects the immune and non-immune components contributing to muscle damage. The relative contribution of each of these pathways to muscle fiber damage is at present unclear. Experiments are currently ongoing to address to address the role of non-immune mechanisms using genomic and proteomic profiling experiments. This basic research is coupled with translational preclinical studies in in vivo and in vitro models to identify specific drugs that either alone or in combination, would reduce the muscle damage and progression in myositis.
