The epigenome represents a dynamic platform of diverse, tissue-specific DNA and histone modifications that robustly influence chromatin structure and function to enable these gene expression programs. The importance of epigenetic control is evident from diseases such as cancer that, in part, reflect defects in chromatin configuration. Similarly, ineffective tissue recovery occurs when epigenomes fail to rewire accurately during cell de-differentiation.

Our prior studies have revealed principles of epigenetic control in developing and maintaining tissue-specific identity (Cell 2016), chromatin states that maintain embryonic memory in adult cells (Molecular Cell 2019), and plasticity of chromatin in adult tissue allowing reversion of differentiated cells into stem cells upon injury (Cell Stem Cell 2017). Accordingly, we view stem cell plasticity in development, disease, and tissue regeneration as an epigenetic problem, and our research program is geared to:

a) investigate fundamental epigenetic mechanisms in development and homeostasis, using the intestine as a model system; and
b) apply the resulting knowledge to modify stem cell behaviors in tissue regeneration and disease.

We try to understand which epigenetic features and configurations favor regenerative potential of differentiated cells, which epigenetic barriers are altered during disease, and how epigenetic alterations may constitute a memory of various cellular states during development and disease. To this end, we use versatile animal models, innovative organ culture systems, and various high-throughput approaches, including single-cell transcriptomic and epigenomic technologies.