Research Projects

Epigenomic profiling has become one of the most important areas in the advancing efforts for personalized medicine, along with genetic tests. Novel epigenomic techniques have led to a better understanding of how expression patterns are regulated by epigenetic changes from tissues to organs, across individuals and health states. These expression changes are in part mediated by specialized cis-regulatory elements called enhancers, which contain DNA motifs recognized by transcription factors to activate transcription. Epigenomic mapping has revealed unexpectedly complex and dynamic enhancer patterns, which share certain stereotypical chromatin features, such as open chromatin, and enrichment for the regulatory histone marks H3K4me1 and H3K27ac (for active enhancers).

The role of enhancers in malignant transformation has been highlighted by the discovery of locus-specific gains and losses in enhancer activity across the epigenome, also known as variant enhancer loci, or tumor-specific enhancers for the locus-specific gains. Moreover, clusters of active enhancers called super-enhancers (SEs) that allow robust transcription of lineage-specific genes also can mediate dysregulated expression of oncogenes, such as MYC. Therefore, aberrant enhancer activity has been shown to be a key driver of tumor formation, maintenance, metastatic progression and drug resistance. Notably, the role of epigenetic changes has become evident during the process of metastasis and in the dynamic process of resistance to therapy.

In the Functional Epigenomics Lab, Dr. Maia's research team is interested in identifying novel biomarkers of drug resistance, exploiting a broad range of some of the most advanced techniques in epigenomic profiling, genome editing-based screens, circulating tumor cell isolation, 3-D organoid cultures and xenograph models derived from people with the disease. One specific interest is PARP inhibitor resistance in ovarian and breast cancer. The research team collaborates with other scientists and clinicians at Mayo Clinic with unprecedented access to samples and clinical data to inform the functional studies and create the most accurate hypotheses for translational research.