My lab is interested in how chromosomes, the long DNA molecules that contain all of our genes, are duplicated and packaged during cellular division. When cells divide, either in order to develop new tissues or to replace aging or defective cells, a precise and highly complex series of events must be carefully coordinated to ensure that newly forming cells inherit the appropriate components and function properly.

Work in my lab is focused on understanding the chromosome cohesion apparatus, how it is regulated during cell division, and how aberrant cohesion contributes to disease. Although the essential mechanisms of cohesion are conserved throughout eukaryotic phylogeny, we are particularly interested in the metazoan elaborations of this system. Aberrant cohesion causes developmental defects and is associated with tumor progression.

The cohesin complex was discovered and initially characterized based on its role in tethering newly replicated copies of chromosomes together from the time they are made until cell division. This cohesion ensures accurate chromosome alignment and segregation in mitosis. Sister chromatid cohesion also supports DNA repair mechanisms that rely on homologous recombination.

In higher eukaryotes, cohesin also plays a critical role promoting normal chromosome structure. Cohesin ensures that chromosomes are packaged into loops and domains. This folding compacts chromosomes and serves to define the transcriptional landscape. Cohesin in this role is thus a critical epigenetic regulator. Cohesinopathies, developmental disorders in individuals with compromised cohesin loading or function, are thought to reflect abnormal gene expression due to changes in chromosome structure.

My interest in cohesin regulation began a number of years ago with my discovery of the essential cohesin regulator Sororin. This activity is not present in fungal systems, which were the basis for our understanding of cohesin regulation at the time. We continue to work on Sororin, and have expanded the scope of study to include other cohesin regulators that are unique to or different in metazoans. We are particularly interested in how chromosome structure can be modulated to respond to DNA damage, to accommodate new transcriptional demands during development, and to promote orderly gene rearrangements in specific cells and tissues.