Our lab studies the molecular mechanisms underlying pluripotency and reprogramming. We employ both proteomic and genomic approaches to identify and study pluripotency protein-protein interaction and transcriptional regulatory networks that govern stem cell pluripotency and somatic cell reprogramming. Insights from these studies will facilitate efficient derivation/generation and optimal propagation of embryonic/induced pluripotent stem cells (ESCs/iPSCs) for their safe application in disease therapeutics and regenerative medicine.
Following fertilization, the totipotent zygote created by fusion of terminally differentiated sperm and oocyte undergoes several cell divisions to give rise to the blastocyst, which is composed of the inner cell mass (ICM) from which pluripotent embryonic stem cells (ESCs) are derived and the trophectoderm that mainly gives rise to the placental tissue. The in vitro capture of pluripotent ESCs under well-defined culture condition for stable maintenance and propagation as well as their potential for regenerative medicine has attracted many including us to study the pluripotency biology. These concerted efforts led to the landmark (Nobel Prize winning) discovery of the generation of induced pluripotent stem cells (iPSCs) in 2006 by Dr. Shinya Yamanaka, who developed an "experimental reprogramming" approach to create iPSCs directly from somatic cells with four transcription factors (Oct4/Pou5f1, Sox2, Klf4 and c-Myc) previously identified as regulators of pluripotency.
Pluripotent stem cells, including ESCs and iPSCs, serve as a potentially inexhaustible source for tissue replacement in regenerative medicine due to their capability of unlimited self-renewal and multi-lineage differentiation. Vital cellular functions of pluripotent stem cells require the coordinated action of a large number of proteins that assemble into an array of multi-protein complexes of distinct composition and structure (protein-protein interactions). In addition, physical interactions between regulatory pluripotency transcription factors and their target genes (protein-DNA interactions) provide insights into differential gene expression dictating the pluripotency program. Analysis of the transcriptional regulatory complexes encompassing intricate protein-protein and protein-DNA interactions is key to understanding maintenance and establishment of stem cell pluripotency.
In contrast to the extensive studies of pluripotency, studies of totipotency are lagging behind due to the difficulty in capturing totipotent stem cells for stable in vitro culture and maintenance. At the present, how cells maintain or acquire totipotency and the exact nature of the cell potency that exists in the zygote and 2-cell stage embryos are still poorly understood.
Our lab is particularly interested in the following four areas of research:
Pluripotent stem cells, including ESCs and iPSCs, serve as a potentially inexhaustible source for tissue replacement in regenerative medicine due to their capability of unlimited self-renewal and multi-lineage differentiation. Vital cellular functions of pluripotent stem cells require the coordinated action of a large number of proteins that assemble into an array of multi-protein complexes of distinct composition and structure (protein-protein interactions). In addition, physical interactions between regulatory pluripotency transcription factors and their target genes (protein-DNA interactions) provide insights into differential gene expression dictating the pluripotency program. Analysis of the transcriptional regulatory complexes encompassing intricate protein-protein and protein-DNA interactions is key to understanding maintenance and establishment of stem cell pluripotency.
In contrast to the extensive studies of pluripotency, studies of totipotency are lagging behind due to the difficulty in capturing totipotent stem cells for stable in vitro culture and maintenance. At the present, how cells maintain or acquire totipotency and the exact nature of the cell potency that exists in the zygote and 2-cell stage embryos are still poorly understood.
Our lab is particularly interested in the following four areas of research:
1. Technique Development and Optimization for Proteomic Studies in Pluripotent Cells.
2. Discovery of Novel Pluripotency Factors in Mouse and Human ESCs/iPSCs.
3. Dissecting the Molecular Mechanisms of Pluripotency and Reprogramming.
4. Exploring and Understanding the Totipotency Biology.
