Lab Website: https://medicine.uiowa.edu/pediatrics/profile/david-gordon

Our laboratory is focused on identifying novel therapeutic approaches for treating pediatric sarcomas

Our laboratory is focused on developing innovative approaches to create genetically defined, as well as biologically relevant, models of cancer in human cells by combining genomic data from the sequencing of cancer genomes with the pluripotent nature of human embryonic stem cells. Using this approach, we have generated a genetically defined model of Ewing sarcoma, a common pediatric tumor, from human stem cells. We then used this model to identify that Ewing sarcoma tumors are uniquely sensitive to drugs that inhibit ribonucleotide reductase (RNR), such as gemcitabine and hydroxyurea. We also identified that inhibition of the checkpoint kinase 1 (CHK1) pathway, which plays a key role in orchestrating the cellular response to DNA replication stress and is activated by RNR inhibitors, sensitizes Ewing sarcoma cell to RNR inhibitors in vitro and in vivo in cell line xenograft experiments. We are now investigating approaches to target DNA replication stress, as well as the cellular response to DNA replication stress, in pediatric sarcomas.

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