ISAL 2025 | Research investigating genes crucial for AML cell survival and potential therapeutic targets

So the work starts under the guidance of Professor Aaron Schimmer at the Princess Margaret Cancer Research Center where I did my postdoc. And we combined functional CRISPR dropout screens to identify genes that are crucial in AML survival and overlaid that with genomic data from RNA-seq about which genes are upregulated at relapse and which genes are upregulated in leukemic stem cells. And when we overlaid these lists, we identified IPO11 as a crucial and possibly relevant target in AML. And then we did some work in silencing IPO11 and showing that once you silence IPO11, you decrease engraftment in PDX models. And IPO11 is a protein that mediates the nuclear localization of other proteins in the cell. So next we try to look at what it actually takes into the nucleus. And we identified UBE2E3 as one of these proteins. And the work that I did is knocking down UBE2E3, seeing that it reduces growth and viability and clonogenicity of AML cells. And next, we try to understand what it does through RNA-seq data and BioID, which is basically a method to map the proteins interacting with a specific protein. And through that, we identified that UBE2E3 interacts with the polycomb repression complex, and specifically with PRC1.1, which was shown before to be critical in AML development. And our work actually demonstrated UBE2E3 positively supports the PRC1.1 activity and gene expression in AML.

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