We develop computational biology methodologies for genomic data analysis and integration, with the aim to understand systems-level gene regulatory mechanisms. Since virtually all the cells in a living organism share the same genome, epigenetic information provides an essential role in regulating cell-type specific gene expression patterns. Our long-term goal is to systematically investigate the structure and dynamics of the gene regulatory network and its role in maintenance of cell-type specificity. To this end, we have developed integrated approaches to identify the chromatin state organization, to determine the targeting mechanism for epigenetic factors, and to reconstruct the gene regulatory network from integration of multiple data-types. We have applied these approaches to stem cells and cancer biology. We actively participate in the ENCODE consortium. We collaborate closely with a number of basic scientists and clinical physicians at Harvard and affiliated hospitals.