Sarah E. Johnstone

Pathologists have observed alterations of nuclear structure for over a century. These morphologic nuclear changes are routinely used in cancer diagnostics, however the molecular underpinnings of these changes remain largely unknown. The Johnstone lab is focused on understanding how nuclear organization is altered in cancer. We center our studies on the epigenetic and topologic packaging of the genome with the goal of understanding the impact that changes in nuclear organization have on transcription and tumor cell phenotype.

Our lab uses both tumor cell models and primary tumor samples and employs sophisticated genomics, imaging and analytic tools to query chromatin structure.  Routine methods include Cut & Run, long-read sequencing (with CpG methylation calling), Micro-C, DNA-FISH and IF.  Our central thesis is that alteration of genome organization impacts transcriptional programs that contribute to malignant phenotypes.  Current projects include defining the mechanistic impact of DNA hypomethylation on the 3D genome and tumor suppression, a deep mapping of nuclear alterations in stepwise models of cancer, defining the structure and epigenetic landscape of cancer neochromosomes and modeling how CTCF and CTCFL mutations impact gynecologic tumors.

We rely on integrated omics analyses to define the relationship between chromatin structure, 3D genome structure and gene expression.  We therefore work closely with computational collaborators at DFCI and members of the lab are closely involved in these collaborations, receiving supportive computational mentorship as well.