• Current Projects

    Defining the role of Meis1 in normal and malignant hematopoiesis

    Translocations of the MLL gene are responsible for the majority of infant- and secondary leukemias. The translocation results in the generation of a fusion oncoprotein which upregulates downstream genes such as Hoxa9 and Meis1 which are known to initiate leukemia in hematopoietic cells. We are studying the role of Meis1 in normal and leukemic hematopoiesis using mouse models with the goal of developing anti-Meis1 therapies as a novel treatment strategy for these leukemias. In normal hematopoiesis, we found that Meis1 is required for the maintenance of quiescent, self-renewing long-term hematopoietic stem cells (LT-HSCs). In the absence of Meis1, reactive oxygen species (ROS) accumulate in LT-HSCs, leading to loss of quiescence and of self-renewal. We also found that Meis1 is required for normal levels of the hypoxia response regulator Hif-1a.

    Defining the role of Meis1 in normal and malignant hematopoiesis
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