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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 (1) how epigenetic modification-mediated dynamic changes in chromatin structure affect gene expression, embryonic development, cell lineage commitment, stem cell pluripotency/self-renewal; (2) epigenetic mechanism of reward-related learning and memory; and (3) how dysregulation of epigenetic factors contributes to the development of diseases such as diabetes, drug addiction, neurological diseases, and cancer. Our laboratory aims to apply this basic research to studying a broad spectrum of human diseases.

Over the past decade, we have worked on a number of projects that span many aspects of epigenetics and chromatin modifications, including identification and characterization of (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; (4) histone H2A ubiquitin E3 ligase PRC1; and (5) the DNA demethylation-related factors such as the Ten Eleven Translocation (Tet) family of 5-methylcytosine dioxygenases. The general approach to these projects involves 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 and various diseases such as metabolic syndrome and cancer. This link is the basis for the establishment of Epizyme, a company focusing on the development of epigenetic-based drugs for cancer.

Built upon our strength in protein biochemistry, the lab has expanded its capability to use a variety of state-of-the-art techniques, including single-cell live imaging, cell lineage tracing in the mouse preimplantation embryo, somatic cell nuclear transfer, stem cell reprogramming, high-throughput epigenetic modification analysis, research on cancer drug resistance, and mouse genetics. Current lines of investigation include:

  1. Dynamic DNA methylation and the underlying mechanisms;
  2. Epigenetic and chromatin changes and their molecular basis of early development;
  3. Epigenetic basis of cell lineage specification, particularly the formation of ICM and trophectoderm cell lineage;
  4. Molecular basis of somatic cell nuclear transfer;
  5. Epigenetic basis of reward-related learning and memory;
  6. Drug resistance in multiple cancer types;
  7. How the information gained from these investigation can be used in the development of treatment for human diseases, such as drug addiction and cancer.

Below are representative figures showing diverse techniques used in the lab:

 

 

fig1
Mouse embryos at different developmental stages
fig2
Mouse ESCs stained with alkaline phosphatase
fig3
Passive dilution of 5hmC during preimplantation development
fig4
Staining of a blastocyst embryo with Oct4 (green) and Cdx2 (red) antibodies
fig5 Staining of an isolated primary human islet with Insulin, Glucagon and PDX1 antibodies
fig6 In vitro cultured cortical neurons
fig7 Staining of a mitotic MII oocyte with tubulin, H4K20me3, and CREST antibodies

 

 
last updated on October 15, 2015