Mechanisms of drug-induced mutations in cancer
About the Project
We invite applications for a PhD study “Mechanisms of drug-induced mutations in cancer“.
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. Surprisingly, with drugs that do not cause DNA damage, we also observe active generation of thousands of very specific mutations. The patterns of these mutations depend on the nature of the drug. Overall, this study challenges an accepted paradigm of “randomness” of mutations and suggest existence of mechanisms of rapid generation of mutations at very specific sites during drug adaptation. We plan to understand mechanisms of active generation of these mutations and uncover factors that guide mutations at specific sites.
In a related project, we uncovered that mutations generated upon development of tolerance to a major drug doxorubicin affect a large number of binding sites of transcription factors and DNA looping, leading to significant changes in transcriptome. Furthermore, these cells become significantly more metastatic than the original cells. We plan to elucidate the connection between the enhanced metastatic ability, changes in genome organization and mutations generated upon such an adaptation. Based on this understanding, we will attempt to improve treatment schemes for patients that develop drug resistance.
Potential PhD students interested in bioinformatics or/and wet lab work are encouraged to apply. Please email me your CV.
Funding Notes
This project is fully funded by the University and the supervisor's grants
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