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Viewed broadly, Dr. Ascherman’s research has investigated the role of cell-mediated immunity in the pathogenesis of idiopathic inflammatory myopathy, a systemic autoimmune disorder resulting in damage to muscle as well as extra-muscular tissues that include skin, joints, lung, and the vascular system. While this effort initially focused on human cells and tissue, the relative rarity of this disorder led Dr. Ascherman to develop a novel antigen-induced model replicating several cardinal features of this disease—namely, myositis and interstitial lung disease. Beyond support for the role of histidyl-tRNA synthetase (HRS=Jo-1) in human disease, this work has generated some intriguing observations regarding the ability of peptides to generate species-specific antibody responses--fueling a computational biology collaboration exploring the contribution of peptide stability to antigenicity, immunogenicity, and affinity maturation. Complementing these studies, more recent work has centered on the interaction between HRS and signaling components of the innate immune system that not only support the development of class-switched autoantibody responses, but also promote a robust myositis phenotype. Dissecting the relationship between HRS-induced innate immune activation, NF-?B-mediated transcriptional pathways, and subsequent transition to antigen driven adaptive immune responses therefore represents a major focus of ongoing work. Additional areas of investigation include biomarker development in autoimmune interstitial lung disease. Collectively, these efforts underscore an expanding basic and translational research program uniting themes of autoimmune disease mechanisms and structural immunology.
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