Jeanne Lawrence is an internationally recognized leader in the study of nuclear structure, genome organization and chromosome regulation by non-coding RNAs. She earlier developed FISH technology for single genes and nuclear RNAs, which made it possible for her lab and others to show that genes and specific RNAs exhibit cell-type organization in compartmentalized nuclear structure. Her lab first demonstrated that the XIST gene, which had been implicated to be involved in X-inactivation, produces a large non-coding RNA that “paints” the whole inactive X-chromosome territory, thereby silencing genes across a whole chromosome. Other recent work provides evidence for the reciprocal structural roles of XIST RNA and abundant repeat-rich hnRNAs that counter euchromatin condensation. In other recent work, her lab has translated basic epigenetic discoveries to a common, largely unaddressed component of the human genetic burden: chromosomal abnormalities, such as Down Syndrome (DS). This innovative approach is based on targeted insertion of an XIST transgene which her lab showed could comprehensively silence trisomy 21, shown in DS patient-derived stem cells. This approach provides several new paths to advance translational research on multiple fronts.