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The primary research interest of our laboratory is to uncover the molecular mechanisms, particularly the alterations of transcription networks via intracellular signaling pathways, underlying stem cell proliferation and differentiation. Over the years, our research group has gained substantial understanding of some of the fundamental working principles of the neurogenic and gliogenic machineries that operate in neural stem/progenitor cells. We discovered that DNA methylation, histone modifications, as well as small non-coding RNA-mediated epigenetic mechanisms play extremely critical roles in neuronal and glial differentiation as well as neuronal maturation, function, and plasticity. The current focus of our research covers two main areas:

1) to uncover the composition and the basic operational principles of the DNA-methylation and de-methylation-related epigenetic gene regulation machineries to address how they dynamically target specific genes within the genome during stem cell differentiation and neuronal activity-dependent cellular events. This line of study will also help to advance our understandings on how nuclear reprogramming occurs during early embryonic development, and how epigenetic state changes during tumorigenesis

2) to establish methods allowing for directed differentiation of human ES cell-derived human neural stem/progenitor cells to obtain large quantity of highly pure subtype-specific neurons, astrocytes, or oligodendrocytes for potential cell-replacement therapies as well as for building novel human ex vivo neuronal models for various neurological diseases with a special focus on Rett syndrome, Huntington’s, Parkinson’s and Alzheimer’s diseases. Collectively, we envision that our research will not only have implications in the studies of disease etiology and therapeutic development for various neurological disorders, but also advance our understanding of the fundamental principles of epigenetic reprogramming, which is critical for the establishment of potential personalized cell therapies using somatic or stem cells.

Research