Our overarching goal is to understand how cells establish and maintain their identity. We are particularly interested in how cardiac cell types are specified, and the implications of this process for congenital heart disease and congestive heart failure. 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 entire 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.
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 dynamic spatial distribution of the genome in the nucleus underlies establishment and maintenance of cell fate and that decoding the rules that instruct nuclear lamina-chromatin interactions will inform how this is achieved. We are interested in:
- Discovery: Comprehensively defining peripheral chromatin domains across human lineages.
- Mechanism: Deciphering how spatial distribution of chromatin shapes cell fate.
- Disease: Determining how nuclear architecture drives laminopathy phenotypes.
We work across disciplines and collaborate with clinicians and scientists of all backgrounds to tackle our questions, using a combination of single-cell, next generation sequencing, live imaging, and proteomic approaches.