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Our research

The nucleosome is a dynamic epigenetic signaling hub for genome-templated processes. We use high-resolution structural biology, protein chemistry, and proteomics to understand the molecular mechanisms that govern epigenetic signaling in health and disease.

 

Determining the structural basis of histone modification cross-talk

By pairing atomic precision protein chemistry to build designer modified nucleosomes and high resolution structural biology, we aim to understand how signatures of epigenetic marks are established and how these signatures control recruitment of chromatin effectors that regulate gene expression, DNA replication, and DNA damage repair. Single particle cryo-electron microscopy (cryo-EM) and macromolecular X-ray crystallography allow us to visualize epigenetic enzymes in action on nucleosome substrates to uncover molecular mechanisms of signal integration on chromatin.

 

Establishing paradigms of nucleosome recognition

Despite decades of research, we still lack a fundamental understanding of how most epigenetic enzymes function in a chromatin environment. We are using proteomics to define patterns of nucleosome recognition with the goal of establishing a universal framework for nucleosome binding.

 

Creating tools to enable epigenetics research

We also are developing new tools to probe epigenetic signaling both in vitro and in model systems. Such tools will allow precise hypothesis-driven interrogation of epigenetic signaling networks.

 

Our Group