Recent Work

Mammalian genomes are astonishingly intricate machines that require finely tuned regulation at multiple levels. Much of this regulation is achieved through the formation of three-dimensional structures, ranging in complexity from simple DNA loops, to discrete organelle-like bodies, to the global organization of chromatin within the nucleus. Since these architectural regulatory programs collectively influence all aspects of genome function, they must be accurately reconstructed as cells divide, and precisely modulated as they differentiate. Unsurprisingly, such processes are also misrelated throughout a host of human pathologies, including neurodegenerative disorders, aging, and cancer.

Although the Importance of nuclear architecture is well established, the mechanisms by which subnuclear structure regulate genome function remain opaque. Even less is known regarding the pathways by which these domains are assembled. Intriguing, noncoding RNAs (ncRNAs) have recently emerged as potentially key components in each of these processes, purportedly nucleating or modulating nuclear structures that span all levels of organization. However, deciphering the function of these putative regulatory ncRNAs has proven extremely challenging, requiring new technologies that probe and manipulate ncRNA activity in situ. To overcome these limitations, Dr. Shechner has developed a suite of such technologies, termed CRISPR-Display, CLING, and IISAAC.