AACR Judah Folkman Career Development Award for Angiogenesis Research
The AACR Judah Folkman Career Development Award
for Angiogenesis Research represents a joint effort to encourage and support a
physician-scientist, who is in the first five years of faculty appointment, to
conduct cancer research and establish a successful career path in this field.
Proposed research projects can be basic, translational, clinical, or
epidemiological in nature, and must substantially advance the field of tumor
Phuong L. Doan, MD
Durham, North Carolina
Epidermal Growth Factor Regulates Leukemic Stem Cell Self-Renewal
Limitations in the cure of acute myeloid leukemia are due to both therapy-related complications and disease relapse due at least in part to leukemia stem cells. Leukemia stem cells may develop resistance to chemotherapy by hijacking the cellular processes of normal hematopoietic stem cells. Using genetic mouse models, Dr. Doan recently described that protection of bone marrow endothelial cells from radiation injury resulted in a corresponding protection of hematopoietic stem cells. Interestingly, these mice had elevated levels of epidermal growth factor in the bone marrow compared to control mice, suggesting that epidermal growth factor signaling was responsible for the acceleration of hematopoietic stem cell recovery. Like normal hematopoietic stem cells, leukemic stem cells may also rely on secreted factors from bone marrow endothelial cells for self-renewal. In the studies for this proposal, Dr. Doan will determine whether epidermal growth factor regulates leukemic stem cell self-renewal, and its impact on both the architecture and function of bone marrow endothelial cells. These studies have high potential significance since epidermal growth factor signaling is an innovative target in acute myeloid leukemia, the mechanisms of leukemia stem cell chemoresistance are largely unknown, and the potential for rapid translation into clinical trials is excellent.
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