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/
et al., 2017, Corrigendum: Acquired CYP19A1 amplification is an early specific mechanism of aromatase inhibitor resistance in ERα metastatic breast cancer., Nat Genet, Vol:49
et al., 2017, Genomic modelling of the ESR1 Y537S mutation for evaluating function and new therapeutic approaches for metastatic breast cancer, Oncogene, Vol:36, ISSN:0950-9232, Pages:2286-2296
et al., 2017, Acquired CYP19A1 amplification is an early specific mechanism of aromatase inhibitor resistance in ER alpha metastatic breast cancer, Nature Genetics, Vol:49, ISSN:1061-4036, Pages:444-450
et al., 2016, Molecular Insights of Pathways Resulting from Two Common PIK3CA Mutations in Breast Cancer, Cancer Research, Vol:76, ISSN:0008-5472, Pages:3989-4001
et al., 2016, Epigenetic plasticity identifies seed breast cancer cells driving drug resistance and metastatic progression, UK Breast Cancer Research Symposium, SPRINGER, Pages:191-191, ISSN:0167-6806