Our work focuses on understanding studying the mechanisms involved in the initiation and progression of cancer and the role of specific oncogenes in this process. Currently we are focused primarily on studying non-small cell lung cancer and pediatric sarcomas (Ewing's sarcoma and Osteosarcoma). We…
more use mouse genetics as a powerful tool that can be exploited to carefully dissect important pathways relevant to human cancer. In addition, we have used comparative genomic approaches to analyze mouse tumor development compared to human cancers. We previously used cross-species gene expression analysis to identify a gene-expression “signature” of oncogenic Kras. Using this signature, we uncovered an unexpected role for Wilm’s tumor-1 (Wt1) as required for oncogenic Kras-signaling in mouse and human cells. Loss of WT1 leads to senescence in cells that express oncogenic Kras. These results led us to hypothesize that other transcription factors required for oncogenic Kras function can be identified using a oncogenic- Kras expression signature as a starting point. We are using more sophisticated computational tools for gene expression network analysis to identify these putative transcriptional regulators of Kras function. In addition, we are interested in using mouse models to understand how tumors become resistant to chemotherapy. Utilizing a mouse model of lung cancer, we have demonstrated that the tumor suppressor p53 is dispensable for the response of lung tumor to cisplatin. We are now using this model of lung cancer to test the hypothesis that cancer stem cells play a role in chemoresistance in lung cancer in vivo.
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