Research / Chromatin regulators

The future of epigenetics

Epigenetic regulatory mechanisms are critical for multicellular development and normal function, as epigenetic deregulation underlies human diseases ranging from cancers to intellectual disabilities (see figure, right). Because epigenetic mechanisms are highly complex and often coupled, detailed mechanistic studies increasingly require both genome-wide and biophysical approaches.

Significant progress has been made in epigenetics due to high-throughput sequencing and related techniques. However, some aspects of these techniques limit further investigation of underlying mechanisms. For example, a major limitation of sequencing-based techniques is the difficulty of detecting short-lived interactions, which make up most nuclear regulatory events. Additionally, because conventional epigenomic assays average over large numbers of cells, they reveal only an average picture of the epigenetic state, obscuring biological heterogeneity. A major challenge for the field is to develop new assays to augment and complement these techniques, to make epigenetics a field based on quantitative, physical principles.

To overcome these limitations, my laboratory will integrate epigenomics with new methods in single-molecule imaging and proteomics. The initial focus of our studies will be ATP-dependent chromatin remodelers, arguably the chief agents of change in the epigenetic landscape. Despite having major impacts on human health, little is known about the systems-level mechanisms by which remodelers drive changes in the epigenetic state. Based on my training, I am in the rare position of being able to integrate “omics” techniques with single-molecule imaging and cell biology, the major approaches needed to address these questions.

My laboratory will be a hybrid experimental/computational lab, where we integrate interdisciplinary techniques to examine fundamental epigenetic mechanisms, as well as reveal how these mechanisms are exploited by disease. Planning for the lab is happening now. If you are interested in the research we are doing, please contact Courtney for more information.

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Multiple scales of epigenetic regulation. Altered function at the molecular scale contributes to misregulation at higher scales, ultimately impacting human health. The initial focus of our lab's studies will be ATP-dependent chromatin remodelers.

Chromatin remodeling in disease. Deregulation of ATP-dependent chromatin remodelers contributes to a number of disorders affecting human health.