The long-term goal of our research program is to decipher the underlying mechanisms of global transcriptional and epigenetic regulations in early embryo development, especially by using embryonic stem (ES) and trophoblast stem (TS) cells as model systems. We are also interested in regulatory factors balancing stem cell differentiation and programmed cell death. CpG island-dependent global gene regulatory mechanisms in various cellular contexts is another topic we have studied.
GENOMICS, SYSTEMS BIOLOGY, AND REGULATORY NETWORKS
We integrate several techniques to address genome-wide regulation during differentiation. These include RNA-Seq (mRNA expression profiling), ChIP-Seq (protein-DNA interactions and histone modifications), and ATAC-Seq (chromatin openness). When combined, we gain a much more comprehensive picture of how transcription factors influence global transcription and regulate the epigenome as cells shift their identity.
PLURIPOTENT STEM CELLS
ES cells and iPS cells possess two special characteristics: self-renewal and pluripotency. Thus, they have been used extensively as a model system for gene regulation, drug discovery, and establishing models of human disease. While factors regulating self-renewal have been well defined, our understanding of differentiation potential remains significantly limited. Since stem cell therapy requires efficient and controlled differentiation, advancing our understanding of both self-renewal and pluripotency would allow us to harness the full potential of pluripotent stem cells in future therapeutic applications.
DIFFERENTIATION VS. PROGRAMMED CELL DEATH DECISION
Apoptosis is essential for embryonic development. Caspases, the effectors of apoptosis, are critical for facilitating cell differentiation and reprogramming as well as guarding against necroptosis. However, excessive apoptosis would lead to embryonic death. Tissue-specific transcription factors (TFs) must orchestrate changes in cellular identity while maintaining a balance between expression of pro- and anti-apoptotic genes. We seek to characterize the apoptotic transcriptional landscape in stem cells and identify TFs that control whether a cell lives or dies during cell fate changes.
TROPHOBLAST LINEAGE DEVELOPMENT
Cells belonging to trophoblast (also known as trophectoderm or TE) lineages are responsible for proper implantation as well as the hematopoietic, vascular, and immunological properties of placenta. Although critical for supporting a healthy pregnancy, the placenta remains as one of the least understood organs in the body. Defects in proper TE lineage development cause early pregnancy failure and other pregnancy-related conditions. We aim to characterize novel key regulators and delineate regulatory networks determining TE lineage development.
CPG ISLANDS AND GENE REGULATORY MODES
CpG islands (CGIs) have long been implicated in the regulation of vertebrate gene expression. However, the role of CGIs in chromosomal architectures and associated gene expression regulations has not yet been thoroughly explored. By combining large-scale integrative data analyses and experimental tools, we seek to understand CGI-dependent global gene regulatory mechanisms.