Our research
Our genome is organized in a polymeric complex called chromatin. This requires cellular machineries that enact and regulate genomic processes, including transcription, DNA replication, and DNA damage repair, to function not just on free DNA, but in a chromatin context. Genomic processes are frequently dysregulated in diseases, especially cancer, and are an emerging area for therapeutic development.
The fundamental repeating unit of chromatin is the nucleosome. Each nucleosome is composed of an octameric spool of histone proteins (two copies each of H2A, H2B, H3, and H4) wrapped by ~145 bp of DNA. The nucleosome serves as a vibrant signaling platform for chromatin through display of a high density and diversity of chemical modifications to both histone and DNA components. These epigenetic modifications are proposed to act in combinatorial epigenetic landscapes that serve as gatekeepers for our genome through recruitment and exclusion of proteins and by tuning local chromatin structure.
By leveraging cutting edge technologies, including cryo-electron microscopy, protein chemistry, and proteomics, we visualize chromatin signaling at atomic resolution to provide new insights into disease pathology and uncover potential new treatments.
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.
Determining the structural basis of histone modifications
By pairing atomic precision protein chemistry to build designer modified nucleosomes and high resolution structural biology, we aim to understand how signatures of epigenetic modifications 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.
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
Recent News
09-05-2025 | Yani’s paper on the role of H2B C-terminal helix PTMs in regulating acidic patch interactions is published in Nucleic Acids Research!
08-07-2025 | Congratulations to Ken on his structure of the KDM6B-nucleosome complex out in Molecular Cell today!
08-07-2025 | New postdoc Jacob Gordon is awarded the 2025 Eshelman Distinguished Postdoctoral Fellowship. Congrats!
05-29-2025 | Congratulations to Dr. Yani Zhao on a masterful PhD defense!
05-22-2025 | Congrats to lab alumnus Aleksandra on being named a Forbeck Scholar!
03-15-2025 | Check out Aleksandra’s paper on APC-histone ubiquitylation in Nature Communications. A great long-term collaboration with the Brown lab!
08-16-2024 | Yani selected for best poster award at Chemical Biology and Medicinal Chemistry retreat. Congrats Yani!
06-03-2024 | Congratulations to new graduate student Caleb on being being selected for the Molecular and Cellular Biophysics T32!
01-10-2024 | Congratulations to Ken on his Nature paper in collaboration with the Gupta, Purvis, and Zhang labs!
01-03-2024 | Aleksandra starts as her position as an Assistant Professor at UC Santa Cruz!
08-24-2023 | Congratulations to Aleksandra on winning the UNC Postdoctoral Award for Research Excellence!
03-16-2023 | Congratulations to Cathy on UNC Dean’s Distinguished Dissertation Award!