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Treatment of cancer with drugs that cause DNA damage often leads to development of the drug tolerance. Recently, we uncovered a novel mechanism of such an adaptation that associates with active generation of hundreds of thousand mutations in chromosomes that prevent drug-triggered DNA damage. We plan to understand how these mutations affect tumorigenic and metastatic properties of cancer cells and use this information to design novel more effective drug combinations and drug treatment schemes.
In a related project, we develop methods based on DNA barcoding to evaluate signaling landscape in cancer cells with a single cell resolution. These methods will be used to monitor the heterogeneity of signaling pathways in cancer cells populations and uncover the mechanisms of such a heterogeneity and it role in drug resistance.
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