Andrew Leavitt, M.D.
	MPL signaling and small RNAs in hematopoietic stem cell development and maintenance
	Email: leavitta@labmed2.ucsf.edu Website:
Selected Publications | Complete Publications

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.

Selected Publications

Eto, K, Murphy, R, Kerrigan, S, Bertoni A, Stuhlmann H, Nakano T, Leavitt AD, and Shattil, SJ. Megakaryocytes from embryonic stem cells implicate CalDAG-GEFI in integrin signaling. Proc. Natl. Acad. Sci., USA 99: 12819-24, 2002.

Kamata T, Kang J, Lee TH, Wojnowski L, Pritchard CA, Leavitt AD. A critical function for B-Raf at multiple stages of myelopoiesis. Blood 106:833-40, 2005.

Gaur M, Kamata, T, Wang S, Moran B, Shattil SJ, Leavitt AD. Megakaryocytes derived from human embryonic stem cells: a genetically tractable system to study megakaryocytopoiesis and integrin function. J Throm Haemost. 4:436-42, 2006.

Nicholas CR, Gaur M, Wang S, Reijo Pera RA, Leavitt AD. A method for single-cell sorting and expansion of genetically modified human embryonic stem cells. Stem Cells Dev. 16:109-17, 2007.

Information last updated April 2007