Our overarching goal is to understand how cells establish and maintain their identity. We leverage classic models of stem cell biology and readily work across disciplines to dissect the underpinnings of how genome organization shapes cell identity and fate. We work on this because it is not well understood how gene programs are coordinately enacted, such as those that happen as a cell progressively restricts. In addition, the promise of cell-based regenerative therapies requires the efficient generation of cells and tissues. We hope our studies will help add to the foundation for these efforts. Some of our efforts on cardiac progenitor lineage restriction and thus we are interested in the implications of our work in understanding congenital heart disease and adult cardiac diseases.
Cell Identity | Genome Organization
The higher-order mechanisms that control cell fate are relatively poorly understood. It has become apparent that the genome is folded and organized in a stereotypical manner in three-dimensional space. We are interested in understanding how the organization of the genome in 3D space establishes and maintains cell identity. Our team focuses on the central hypothesis that proper genome folding and dynamic spatial organization of the genome in the nucleus underlies the establishment and maintenance of cellular identity. We believe that decoding the rules that instruct genome organization and lamina-chromatin interactions will inform how this is achieved. We are interested in:
- Discovery: Comprehensively defining peripheral chromatin domains and genome folding across human lineages.
- Mechanism: Deciphering how genome folding and spatial organization of chromatin shapes cell fate.
- Disease: Determining how nuclear architecture drives disease phenotypes, such as those arising in laminopathies and other congenital (heart) diseases
We work across disciplines and collaborate with clinicians and scientists of all backgrounds to tackle our questions, using a combination of mouse genetics, iPSC-differentiation, single-cell, next-generation sequencing, advanced imaging, and proteomic approaches.