Molecular characterization of Ahi-1, a novel signaling molecule with an SH3 and multiple WD40-repeat domains, in normal and leukemic hematopoiesis

Because many forms of leukemia originate in blood stem cells, uncovering the changes that occur in these cells is crucial to understanding how these diseases develop and progress. Dr. Xiaoyan Jiang is studying Ahi-1, a newly-discovered oncogene (cancer causing gene) that is involved in murine leukemia development (leukemia in mice) and shows abnormal expression in human leukemic cells, including leukemic stem cells from patients with chronic myeloid leukemia and Sezary cancer cells from patients with cutaneous T-cell lymphoma. Her research team recently found that over-expression of Ahi-1 gene alone can cause leukemia in mouse models and suppression of Ahi-1 gene can normalize its transforming activity in human leukemia cells, a strong indicator that Ahi-1 is likely to be an important new oncogene involved in the development of leukemia in humans. Dr. Jiang’s research will explore the normal function(s) of Ahi-1 in the development of blood cells, and how this is altered when cells become leukemic. This research will also begin to identify new intracellular molecules that interact with Ahi-1 and the cellular and molecular pathways through which these interactions occur. Understanding how and by which pathways Ahi-1 contributes to the development of leukemia may provide important new molecular targets for the development of targeted cancer treatment that will be more effective and have fewer side effects than currently used chemotherapy.