The lab is primarily interested in how the genome is organized and maintained in the eukaryotic cell nucleus. Understanding genome organization is particularly important during development and differentiation when cells acquire a specific identity. Genome organization relies on the dynamic properties of chromosomes. Chromosomes are tethered to the nuclear envelope and intermingle within the nuclear interior, generating hotspots of gene expression. At these locations, sets of genes or gene programs are believed to be co-expressed, prompting cellular function. With this in mind, to learn how the genome is organized during development and differentiation, we investigate the mechanisms that facilitate spatial and temporal chromatin and RNA changes, and how they may be altered in disease.
We are currently studying the emerging role of cytoskeletal proteins — actin and myosin — in the 3D organization of the genome and the potential for these mechanisms to confer stability to the eukaryotic genome. We focus on actin- and myosin-dependent epigenetic changes at both chromatin and RNA level that occur in proliferative and differentiated cellular states. We address these questions at both molecular and systemic levels, using a combination of genome-wide approaches and transdifferentiation techniques. These experimental approaches have allowed us to examine the importance of actin and myosin in epigenetic control mechanisms for nuclear organization during neuronal development.
In the long term, we are interested in how impaired mechanisms of genome organization correlate with the acquisition of cellular pluripotency and the onset of neurodegenerative diseases.