The cells of different tissues have the same genome but are phenotypically distinct. Cell identity programs are thus epigenetic in nature, as they are not driven by changes in the DNA sequence. How do these epigenetic processes work, and why are we so interested in and fascinated by them?
We study the contribution of chromatin states to epigenetic programs. Covalent modifications of histones and DNA offer a powerful mode for encoding and propagating epigenetic information. Long-standing models of lineage specification propose that epigenetic processes help enforce cell fate decisions and maintain differentiated cellular identities. However, the mechanisms by which transient stimuli are converted into stable cell fate outputs are poorly understood.
A few of the questions we seek to answer are:
What are the “locking” factors that impose a given cellular identity, and can they be manipulated to induce cellular plasticity?
How are cell identity gene expression programs faithfully propagated over time and across the cell cycle?
What is the molecular logic that allows stem cells to differentiate but precludes de-differentiation of mature cells?
These problems of basic cellular biology have significant health ramifications. For example, cancers such as acute myeloid leukemia (AML) are poorly differentiated and driven by cancer stem cells. The induction of latent differentiation programs represents a powerful therapeutic approach for these malignancies, but is hampered by our limited understanding of how epigenetic factors constrain cellular plasticity. A deeper understanding of this process will advance our ability to manipulate cellular identity in selected pathologies.
By using a combination of genetic screening, epigenomic profiling, and chromatin-focused biochemistry, we aim to address these and related questions.