Grant: $53,900 - National Institutes of Health - Sep. 25, 2009
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Award Description: Development of brain tumor therapies directed against brain tumor stem cells.
Project Description: Since the discovery of neural stem cells, a connection between these cells and the origin of brain tumors has been theorized. The recent discovery by us and others of brain tumor stem cells and their close phenotypic relationship to neural stem cells has prompted us to explore proliferative mechanisms that are in common between neural stem cells and brain tumors. We have previously found that maternal embryonic leucine zipper kinase (MELK), a serine-threonine kinase, is a marker for and regulates the proliferation of self-renewing neural progenitors (neural stem cells) in developing mouse brain. We have also found that MELK expression correlates with brain tumor grade and survival and that it is a 'hub' gene; one whose expression predicts the expression of numerous other cell cycle genes. We hypothesize that MELK is an important regulator of brain tumor proliferation, mediates the self-renewal of brain tumor stem cells and serves as a marker for brain tumor stem cells. However, further studies are needed to determine if MELK and its putative molecular pathwaywill serve as targets for brain tumor therapy. This proposal will address these issues. We will first perform experiments to determine whether MELK mediates the proliferation of brain tumor cell lines, focusing on medulloblastoma and glioblastoma multiforme (GBM). These tumors were chosen because they are common and there is strong preliminary evidence supporting the hypothesis that MELK regulates their function. Also, since the presence of brain tumor stem cells in medulloblastoma has been questioned, it will be important to determine whether MELK functions in a different capacity in these tumors compared to GBM. We will establish the mechanisms underlying MELK effects by determining MELK's role in regulating the cell cycle, the genes that mediate its function, and whether this function is mediated by its kinase domain or the domain critical for a function in RNA processing. We will also determine whether MELK
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Project Status: Not Started
This award's data was last updated on Sep. 25, 2009. Help expand these official descriptions using the wiki below.