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Kundu: Role of autophagy in erythropoiesis and tumorigenesis

Ultrastructural studies suggest that autophagy plays a vital role in the erythrocyte maturation, particularly during the final stage of maturation as reticulocytes become devoid of most intracellular components (including RNA, ribosomes and organelles) and assume the flexible bi-concave discoid shape that is characteristic of mature red blood cells. Despite the morphological evidence of autophagy during reticulocyte maturation, its role in organelle degradation during erythropoiesis has not been examined using a genetic approach. Ulk1 (but not Ulk2) expression is normally induced during erythroid maturation in a manner suggesting a role for Ulk1 in reticulocyte maturation. To address the role of Ulk1 and Ulk2 in erythroid maturation, we are using in vivo and ex vivo assays to assess erythroid maturation in conditional knock-out mouse models. We are also using these mice to examine the hypothesis that defects in autophagy and in the ability of cells to eliminate damaged mitochondria can contribute to the pathogenesis of hematopoietic malignancies.