Research in the Luxton Laboratory is broadly focused on cellular mechanotransduction, or the fundamental ability of cells to sense and respond to mechanical cues by converting them into chemical signals or gene expression. Mechanotransduction is essential for cellular differentiation, division, migration, and survival. Accordingly, impaired mechanotransduction underlies the pathogenesis of the following human diseases: cancer, cardiomyopathy, muscular dystrophy, and neurodegenerative diseases. Therefore, a mechanistic understanding of mechanotransduction promises to advance multiple fields of cell biology as well as human health. We are particularly interested the role of the nucleus as a key mechanotransducer of externally applied forces and extracellular stiffness into biochemical cues that regulate signaling and gene expression. To understand nuclear mechanotransduction, we study the assembly and function of the conserved nuclear envelope-spanning linker of nucleoskeleton and cytoskeleton (LINC) complex, which mechanically integrates the nucleus with the cytoskeleton. Despite their central role in nuclear mechanotransduction, the mechanisms underlying functional LINC complex assembly and its regulation in cells generally and neurons in particular remain poorly defined. Moreover, the contribution of defective LINC complex-dependent nuclear mechanotransduction to human disease pathophysiology mechanisms, especially those of neurological disorders and neurodegenerative diseases, is unclear. To address these critical knowledge gaps, I employ a suite of cutting-edge biophysical, cell biological, quantitative imaging, and synthetic biological approaches as well as several model systems such as cultured mammalian cells (human and mouse), the African clawed frog Xenopus laevis, and the social amoeba Dictyostelium discoideum. Our current and future efforts are devoted to further defining the mechanistic role of impaired mechanotransduction in the pathophysiology of the neurological movement disorder dystonia at the molecular, cellular, and circuit levels. These studies will lay the foundation for the development of novel therapeutic strategies for the treatment of dystonia as well as other neurological and neuropsychiatric disorders caused by mutations in LINC complex proteins for which no cures currently exist.