The Wang Laboratory of Human Environmental Epigenomes
Meet Our Team
- Office: 410-955-7840 Lab: 410-614-5049
- 615 North Wolfe Street, Baltimore, Maryland 21205
Office: E7618 | Lab: W7710
The long-term goal of the Wang laboratory is to determine how epigenetic codes, including patterns of DNA methylation and combinatorial patterns of simultaneously occuring histone modifications, are established and how this establishment goes awry upon environmental stimuli, thus contributing to human diseases (such as cancers and autoimmune diseases).
- Toward our goal, we developed a high throughput method ChIP-seq, by coupling chromatin immunoprecipitation with deep sequencing, and characterized the human histone methylome (20 histone methylations; Cell, 2007) and histone acetylome (18 histone acetylations; Nature Genet, 2008). It is the data sets of this stripe that allows us to decode the "histone code" that different histone modifications, including histone acetylations and methylations, may modulate gene activity in a combinatorial way, potentially acting as different codes.
- We identified numerous combinatorial patterns that are associated with different genes and a "backbone" composed of 17 active marks to regulate the expression of more than 3000 genes (Nature Genetics, 2008), reviewed in (Curr Genet and Dev, 2009). To understand how these combinatorial patterns are established, we did global characterization of histone acetyltransferases (HATs) and deacetylases (HDACs). We surprisingly found that corepressor HDACs bind to active genes with histone acetylations but not silent genes (Cell, 2009), which changes the long-held OLD dogma, reviewed in (Nat Rev Genet, 2010).
- Part of our work in the laboratory is to establish a new model that we called “dancing with the enemy" to understand how the association of both HATs and HDACs with active genes regulates gene expression. We aim to understand how abnormal acetylation patterns reprogram gene expression, thus contributing to the pathogenesis of environmental diseases.
- To understand the patterns of DNA methylation, in collaboration with Yi Zhang's group we recently characterized the DNA 5mc-5hmc methylome (Genes Dev, 2011). Our further ChIP-seq analyses of Tet1 suggest that Tet1 plays a role in the establishment of dynamic DNA methylation patterns (Nature, 2011). By understanding the establishment mechanism of DNA methylation patterns in normal cells, we aim to elucidate the processes that lead to abnormal DNA methylation patterns in human diseases. For example, cancer cells are characterized by promoter-region specific hypermethylation and global hypomethylation. Autoimmune diseases also have the problems of global hypomethylation.
- In the Wang laboratory, we take advantage of our developed high throughput methods including ChIP-seq, RNA-seq, and BS-seq (bisulfite sequencing). Recently, we began to work on single-cell RNA-seq to tackle some really interesting questions. These global strategies allow us to make a final conclusion based on the genome-wide analysis data.
The Wang Laboratory of Human Environmental Epigenomes is housed in the Department of Environmental Health and Engineering at the Johns Hopkins Bloomberg School of Public Health. Dr. Wang teaches courses as part of the PhD Track in Toxicology, Physiology & Molecular Mechanisms, and teaches a lecture in the course, The Molecular Basis of Environmental Health.