Our laboratory studies the spatial organization of the genome, with implications for gene regulation, genome integrity, and diseases such as cancer, aging, and neurodegenerative disorders. We use Drosophila and mammals in combination with cellular, molecular, genetic, and computational tools to elucidate how chromosomes are functionally organized in 3-D space and time. We also develop and utilize new technologies that use fluorescent in situ hybridization (FISH) to interrogate chromosome positioning at single-cell resolution. These include a pipeline for high-throughput FISH (Hi-FISH), and a new type of probe, called Oligopaints, which reduces the cost and increases the resolution of FISH.
Our approach leverages the flexibility and scalability of Oligopaints to generate low-cost chromosome paints for systematic analyses of chromatin folding and positioning. Typically, studies of chromosome positioning have been stymied by the lack of
The major feature that stands out in the nucleus of all metazoan genomes are the chromosome territories (CTs), which have nonrandom radial positions that are conserved through evolution. We are using our custom Oligopaint FISH probes to
Although chromosome interactions are a fundamental aspect of nuclear organization little is known about how they are established, regulated, and inherited across cell divisions. To address this gap, we developed a fully automated FISH-based imaging
Cornelia de Lange Syndrome (CdLS) is a developmental disorder characterized by congenital abnormalities, intellectual disability, and multi-system clinical symptoms including congenital heart disease. The disorder typically manifests due to mutations in
The emerging view is that interactions between regulatory elements and promoters are insulated within extensive self-interacting units termed topologically associated domains (TADs), which are further positioned in the nucleus to spatially segregate active and