The AACR Judah Folkman Career Development Award for Angiogenesis Research is open to junior faculty who completed postdoctoral studies or clinical fellowships no more than three years prior to the start of the grant term; who are in their first full-time, faculty appointment and hold the title of instructor, research assistant professor, assistant professor or an equivalent full-time faculty appointment; and who are at an academic, medical or research Institution. Research projects are restricted to basic, clinical, translational or epidemiological projects that substantially advance the field of anti-angiogenesis research in cancer.
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.