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Summary: Yi Zhang is interested in how epigenetic-mediated dynamic changes in chromatin structure affect gene expression, cell lineage commitment, stem cell pluripotency and self-renewal, and cancer development. His long-term goal is to apply this basic research to studies of human diseases.

Epigenetic modifications, particularly DNA methylation and covalent histone modifications, play an important role in regulating chromatin dynamics and therefore have a significant impact on gene expression. Our lab is interested in how epigenetic-mediated dynamic changes in chromatin structure affect gene expression, cell lineage commitment, stem cell pluripotency, and self-renewal. We are also interested in how misregulation of epigenetic factors contributes to the development of diseases such as diabetes and cancer. Our long-term goal is to apply this basic research to studies of human diseases.

Over the past 10 years, our lab has worked on a number of projects that span many aspects of epigenetics and chromatin-modifying enzymes, including (1) the ATP-dependent nucleosome-remodeling and histone deacetylase complex NuRD; (2) various histone methyltransferases, such as EZH2, hDOT1, ESET, SET7, SET8, and PRMT1; (3) various histone demethylases, such as the JmjC family proteins, JHDM1A, JHDM2A, JHDM3A, RBP2, PLU-1, JMJD3, UTX, and Lid; and (4) histone H2A ubiquitin E3 ligase PRC1. The general approach to these projects involved biochemical purification and functional characterization of these enzymes in vitro and in cell culture, followed by biological characterization in mouse models. The proof-of-concept studies have uncovered a link between several of these enzymes to cancer. This link was the basis for the establishment of Epizyme, a company focusing on the development of epigenetic-based drugs.

	Mouse embryonic stem cells...

Building upon our strength in protein biochemistry, our lab has recently broadened our research interests to include a focus on development and reprogramming.

Current lines of investigation include the following:

1. Dynamic DNA methylation and the underlying mechanisms
2. Epigenetic and chromatin changes and their molecular basis during early development
3. Epigenetic basis of cell lineage specification, particularly the formation of inner cell mass and trophectoderm cell lineage;
4. Epigenetic mechanism of induced pluripotent stem (iPS) cell generation and its application in pancreatic β-cell generation
5. Role of long noncoding RNAs in epigenetic and chromatin regulation
6. The use of the information gained from these investigations for the development of treatments for human diseases, such as diabetes and cancer

To address questions in these areas, we have expanded our ability to perform a wide range of state-of-the-art biological techniques, including single-cell live imaging, cell lineage tracing in the mouse preimplantation embryo, pancreatic β-cell differentiation, iPS cell generation and differentiation, stem cell reprogramming, bone marrow and pancreatic cell transplantation, and mouse genetics.

Last updated June 21, 2010