Hematopoiesis is a life-long developmental process that requires an adequate pool of hematopoietic stem cells (HSC) that continuously generate the required number of circulating mature blood cells. Understanding the mechanisms underlying the development and maintenance of HSCs should improve our ability to treat a variety of hematopoietic disorders.
Our laboratory is using human embryonic stem cells to begin to understand the role of small RNAs in the formation of HSCs. We are also interested in understanding the role of MPL signaling in HSC generation and maintenance, including the role of down steam signaling through Raf kinase family members that are activated during MPL signaling. Thrombopoietin (TPO) is the cognate ligand that activates MPL signaling, and the loss of MPL signaling in mice and humans results in a quantitative HSC defect. Our lab is using murine model systems and human embryonic stem cells to better define the role of MPL signaling in HSC development and maintenance. MPL signaling is also important in megakaryocytopoiesis, and we are using similar systems to understand how MPL signaling functions in this somewhat enigmatic branch of hematopoiesis.