Development follows a complex decision tree where cells become increasingly specialized. These decisions involve a network of cell signaling, transcriptional and post-transcriptional regulation. A better understanding of these events are essential in order to direct the differentiation of stem cells in a controlled fashion in the petri dish. One increasingly appreciated component of this network is the role of non-coding RNAs. In particular, microRNAs appear to play an essential role in stem cell differentiation. We are dissecting their role using a combination of tools to knock-out and over-express microRNAs in stem cells both in vitro and in vivo. We are particularly interested in the role of microRNAs in neural differentiation.

Malignant tumors consist of a mixed population of cells. It is now clear that in most tumors only a small fraction of the cells maintain tumorigenic potential. That is, only a small fraction of the cells can initiate a new tumor when transferred to another site or host. These cells express many of the same markers expressed in stem cells during normal development. This would suggest a stem cell origin of tumors. We are actively testing this hypothesis as well as dissecting the earliest events of tumorigenesis within stem cell populations.