Our lab is interested in understanding how nuclear organization contributes to transcriptional control through two lines of investigation. Our studies use molecular and genetic approaches, using Drosophila as a model system. First, we study a class of conserved DNA elements known as insulators that establish independent transcriptional domains within chromosomes. Insulators play a critical role in many developmental processes, such as imprinting and mammalian dosage compensation. Loss of insulator function is associated with genome instability, as evidenced in congenital forms of myotonic dystrophy. Second, we investigate regulatory contributions of the nuclear lamina, the protein meshwork underneath the nuclear envelope (NE) that contributes to chromosome organization and gene regulation. Our studies are directed to LEM domain (LEM-D) proteins that bring chromosomes to the nuclear periphery. Although LEM-D proteins are globally expressed, loss of these proteins causes tissue-restricted diseases, such as Emery-Dreifuss muscular dystrophy (EDMD), cardiomyopathies and bone density disorders. We find that loss of these proteins disrupts key developmental signaling cascades, with evidence for a role in stem cell homeostasis. We are defining how LEM-D proteins regulate nuclear lamina function to understand the role of these proteins in developmental processes that include maintenance of stem cell function.