Cancer cells exhibit altered transcriptional profiles when compared to their tissue of origin. Genetic alterations participate in promoting defective transcription, however they don't explain the full spectrum of aberrations found in malignant tissues. Gene expression is also controlled via modifications of the chromatin landscape including DNA methylation, histone modifications and chromatin remodelling. Our objective is to characterize the role of the chromatin landcape in oncogenesis. A second goal is to understand how cancer cells reprogram the chromatin landscape to escape treatment.
We have used breast cancer models to demonstrate that epigenetic reprogramming of the chromatin landscape promotes the expression of genes directly related to resistance to endocrine therapies. We can create epigenomic maps to study the regulatory networks of cancer cells and determine how these networks respond to therapies. Ultimately, we want to exploit epigenetic mapping to identify druggable targets, biomarkers and develop novel compounds to interfere with reprogramming.
My lab is also interested in understanding the extent of interactions existing between genetic and epigenetic alterations. Cancer cells likely exploit both genetic and epigenetic mutations to promote proliferation, adaptation and invasion.
More information can be found here http://cancer-epigenomics.com/
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et al., 2018, TGF-beta induces miR-100 and miR-125b but blocks let-7a through LIN28B controlling PDAC progression, Nature Communications, Vol:9, ISSN:2041-1723