Targeting Chromatin Remodeling to inhibit Tumor Metastasis

Chromatin remodeling complexes are ATP-dependent enzymes that regulate all DNA dependent processes by moving, exchanging orevicting nucleosomes from the underlying DNA. These epigenetic modifiers play important roles in cellular homeostasis and are preferentially mutated in many diseases and cancer. Baz2a is aremodeling protein that is targeted to the genome by non-coding RNAsand highly upregulated in breast cancer. We aim to screen for small molecule inhibitors of Baz2a RNA interaction to block its tumorigenic potential and to evaluate these in a breast cancer model.

We will further study the dynamic changes of chromatin structure during progression to metastatic cells by determining nucleosome positioning and chromatin architecture and their impact on the transcriptome. The study will include ATAC-Seq, MNase-Seq, transcriptiomics and bioinformatics.