Understanding the biological mechanisms underlying stem cell biology is important for development and implementation in the field of regenerative medicine. Recent reports have shown that small RNAs play an essential role in stem cell biology though less is known about their regulation. A signature of embryonic stem cell-specific 
microRNAs is required for maintaining stem cells in an undifferentiated state, but little is known on their exact function and regulation of expression.
Our lab is an ideal position to explore this area, since we culture both mouse and human embryonic cells, and command powerful RNAi screening systems. Specifically, we are discovering how embryonic stem cells regulate their expression of microRNAs.
In addition to the above area, we have a collaboration with the Leavitt Laboratory at UCSF to study the roles of microRNAs in the differentiation of embryonic stem cells into specific hematopoietic lineages. Hematopoietic stem cell transplantation is the treatment of choice for many hematologic malignancies, and it is used to treat an expanding number of congenital blood disorders. However, only ~30% of patients who can benefit from this treatment have a matched sibling that can serve as the ideal donor.
Human embryonic stem cells, with their unlimited self-renewal capacity and their ability to generate all human cell types, provide a novel and exciting opportunity to obtain hematopoietic stem cells, thereby filling a critical therapeutic void. However, many hurdles remain before this vision can be realized, including the identification of more optimal human embryonic stem cell lines and better methods to direct the development of specific cell types from embryonic stem cells.
Our Leavitt:McManus teamwork seeks to shed new insight into how we might use microRNAs to better control and direct the development of human embryonic stem cells into therapeutically useful hematopoietic stem cells that can be used for transplantation. Our work is funded by the CIRM.