Chromatin and Genome Integrity in Cancer
Endogenous and exogenous factors are constantly threatening the integrity of our genomes. Cells respond to genetic insults by mounting a complex signaling system collectively termed the DNA damage response (DDR). Many DDR activities engage epigenetic mechanisms involving chromatin, the protein-DNA complexes that organize the eukaryotic nuclear genome and promote both epigenome and genome functions.
Our research aims to understand genome maintenance and the DNA damage response in the context of chromatin, cancer and anticancer therapies. Determining the interplay between the DDR and chromatin is fundamental for elucidating how cells maintain both epigenetic and genome integrity, which is critical in diseases including cancer where genome and epigenome instability are common.
In addition, many cancer therapies function through damaging DNA and drugs that target the cancer epigenome are being developed as innovative therapeutic strategies. We are addressing these questions using multifaceted and diverse approaches including genetics, genomics, genome-editing, cell biology and molecular biology in human cancer cell models.
Through these efforts, we hope to define the functional relationship between chromatin and genome integrity pathways and how these mechanisms contribute to cancer. This information can be leveraged to develop and utilize cancer therapeutic strategies involving epigenetic regulators and DNA damage response mechanisms, which include clinically relevant inhibitors of PARP, HDACs, DNA methylation and bromodomain proteins, as well as radiation and DNA damaging therapeutic agents.