研究兴趣

My lab studies how to control stem cell fate through modulating the two interconnected layers, metabolism and epigenetics.



In around 2009, the ground-breaking induced pluripotent stem cell technology was very low efficient and we aimed to improve it through understanding how it works. Knowing the difference in metabolism between somatic and embryonic stem (ES) cell, we first postulated that mitochondrial reactive oxygen species (ROS) might inhibit reprogramming. We tested a spectrum of antioxidants and identified only vitamin C could (Vc) dramatically enhance reprogramming efficiency, independent of its well-known antioxidant activity. Actually, Vc can activate a group of histone and DNA demethylases to remove epigenetic barriers in somatic cells and during reprogramming. Until today, the roles of only a few demethylases and their targets in reprogramming, stem cell and development have been clarified but a lot more others await future exploration.



Recently, we asked how the whole intercellular organelle system is remodeled during somatic cell reprogramming. Initially we postulated that autophagy may mediate this cellular remodeling. Surprisingly however, we discovered that it’s not autophagy but its upstream repressor, mTORC1, that regulates cytoarchitecture through mitochondrial biosynthesis. Autophagy and mTORC1 are evolutionarily conserved metabolic regulators and in vivo studies support their important roles in stem cell maintenance and aging. How exactly they function, be regulated and linked to epigenetic state of stem cells are still largely unknown and very important issues.



We believe understanding deeper how mTORC1 and autophagy control the metabolic and epigenetic state of stem cell may provide us new important clues for how to promote longevity.