Research
Overview
Our laboratory is interested broadly in the question of how chromatin folds into chromosomes, how these chromosomes fold and position within the interphase nucleus, and how this nuclear genome organization impacts DNA functions such as transcription
and DNA replication timing. We use a combination of new sequencing-based assays we have developed to probe both chromosome positioning in the nucleus relative to specific nuclear locales and large-scale chromatin compaction and microscopy approaches including live-cell imaging of tagged genes, RNAs, and proteins.
Current Research
In recent years we have used a combination of live-cell imaging and single molecule RNA FISH to demonstrate an increased gene expression of certain genes within just a few minutes of contacting nuclear speckles. Using our laboratory’s TSA- seq method, we have shown that differences in gene expression genome-wide among different cell types is best correlated with relative distance to nuclear speckles, as compared to other nuclear locales.
Most recently we have identified additional nuclear condensates extending from nuclear speckles that might explain this link between gene expression and distance to nuclear speckles. Currently we are testing possible links between gene positioning, directional gene movement, transcription factors, and gene expression. We are also exploring to what degree these links might be mediated by the dynamics of one or more perispeckle nuclear compartments that we have identified and are now characterizing.
Finally, we are beginning to explore how changes in gene positioning and large-scale chromatin compaction might be linked to changes in gene expression during the cell cycle, changes in cell proliferation, and other physiological processes using these new genome-wide assays are laboratory is developing.