miR-23a Cluster and miR-10a Regulation of Self-Renewal and Survival Pathways in Human Hematopoietic Stem-Progenitor Cells and Acute Leukemia Cells
The goals of this project are to investigate the regulation of genes and pathways involved in self-renewal and survival pathway in leukemia stem cells (LSCs) by small molecules called microRNA. Two of these microRNAs, the mir-23a cluster and miR-10a, function as tumor suppressors in leukemia and Dr. Scheibner’s lab proposes that decreased expression of these tumor suppressor microRNAs contributes to de-regulation of self-renewal and survival pathway in LSCs, and that their over-expression will target LSCs and reduce their frequency in the leukemia population. They also predict that these microRNAs will make the LSC population more susceptible to drug treatment. Conversely, her lab predicts that high endogenous levels of the miR-23a cluster and miR-10a found in the normal population of adult blood stem-progenitor cells inhibit their expansion and survival. Dr. Scheibner’s lab is also investigating if manipulation of their expression will lead to expansion of this population. Success of this proposal may lead to novel molecules for developing leukemia treatment strategies, and reveal mechanisms of stem cell expansion, useful not just in adult blood stem cells, but in other stem cell populations, and for the continuing development of stem cell therapies.