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Amy J. Wagers, Ph.D.

Dr. Wagers is a Principal Investigator in the Section on Islet Cell and Regenerative Biology as well as an Associate Professor of Stem Cell and Regenerative Biology at Harvard Medical School. She received her doctoral degree in Immunology and Microbial Pathogenesis from Northwestern University, and completed postdoctoral fellowship training in the laboratory of Irving Weissman, M.D., at Stanford University School of Medicine. She is a recipient of a Burroughs Wellcome Fund Career Award in Biomedical Sciences, a Smith Family New Investigator Award and a Howard Hughes Medical Institute Early Career Science Award. 

Every year more than 45,000 patients undergo bone marrow transplantation for the treatment of diverse diseases, including leukemia, lymphoma and immunodeficiency. The success of these transplants depends on the surprising ability of infused blood-forming stem cells to accurately and efficiently migrate to the bone marrow of recipients and, once there, to expand and repopulate the patient’s blood with mature, functioning cells. While successful blood cell transplantation vastly extends the life span and improves the quality of life of many people, significant transplant-related mortality still occurs. Improving outcomes for transplant patients requires a better understanding of the mechanisms by which blood-forming stem cells engraft bone marrow, expand and develop into each of the required types of mature blood cells.

Blood-forming stem cells are generally found in the bone marrow; however, at any given time, a very small number of cells can also be found in the bloodstream. The relationship of these blood-borne stem cells to blood-cell production had been unclear until recently, when Dr. Wagers and her colleagues discovered that these cells are actually in the process of migrating from one bone marrow location to another. Stem cells that travel through the blood can re-engraft distinct bone marrow sites and continue to contribute to normal blood-cell production. Thus, blood-forming stem cells are in a constant state of movement, which may help explain the success of bone marrow transplantation by suggesting that the infused stem cells take advantage of a migration pathway that already exists for their recirculation.

Because the mechanisms and regulators of these events are largely unknown, one aim of Dr. Wagers’ research is to identify and characterize molecules that control the migration and function of blood-forming stem cells.  Such studies could ultimately enhance the success of clinical transplantation and, given recent evidence suggesting the potential benefits of blood cell transplantation in the treatment of type 1 diabetes (including termination of ongoing autoimmunity, induction of tolerance to subsequent islet transplantation and possibly also the stimulation of beta-cell proliferation or regeneration), may significantly impact available approaches for the treatment type 1 diabetes.

Currently, blood-forming stem cells are the only adult stem cells that scientists can purify and use for treating human disease. To develop robust cell therapies for treating non-blood-related disease, scientists must identify cells with equivalent regenerative function for non-blood tissues. Some investigators suggest that blood-forming stem cells themselves could be used to regenerate multiple organs; however, thus far, Dr. Wagers’ research has found no evidence to support a significant contribution from blood or bone marrow sources to the regeneration of non-blood tissues. Therefore, Dr. Wagers began studies to identify tissue-resident stem cell populations that function robustly to regenerate damaged adult tissues, and recently succeeded in isolating a novel population of adult skeletal muscle precursor cells with robust ability to repair damaged muscle.  Future studies of these cells will help to define the mechanisms that support the formation of new skeletal muscle and identify signaling pathways and gene expression programs important for maintaining these muscle stem cells. 

Dr. Wagers also plans studies to identify additional tissue-specific stem cell populations that can regenerate damaged adult tissues. This comprehensive analysis may ultimately suggest new treatment options for multiple degenerative disorders.

Selected References
Sherwood RI, Wagers AJ. Harnessing the potential of myogenic satellite cells.Trends Mol Med Epub Apr. 2, 2006.
Passegue E, Wagers AJ, Giuriato S, Anderson WC, Weissman IL. Global analysis of proliferation and cell cycle gene expression in the regulation of hematopoietic stem and progenitor cell fates. J Exp Med 202:1599-1611, 2005.

Wagers AJ, Weissman IL. Plasticity of adult stem cells. Cell 116:639-643, 2004.

Sherwood, RI, Christensen JL, Conboy IM, Conboy MJ, Rando TA, Weissman IL, Wagers AJ. Isolation of adult mouse myogenic progenitors: functional heterogeneity of cells within and engrafting skeletal muscle. Cell 119:543-554, 2004.

Wagers AJ, Sherwood RI, Christensen JC, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 297:2256-2259, 2002.

Wright DE, Wagers AJ, Gulati AP, Johnson FL, Weissman IL. Physiological migration of hematopoietic stem and progenitor cells. Science 294:1933-1936, 2001.