Research
Dr. Haynes' research aims to identify how the intrinsic properties of chromatin, the DNA-protein structure that packages eukaryotic genes, can be used to control cell development in tissues. Her lab investigates and designs chromatin-based systems for controlling gene expression in cancer and other cells that are relevant to human health.

The Haynes group uses histone-binding protein motifs to build fusion transcription factors that co-regulate groups of genes based on their chromatin features. They call the approach "macrogenomic engineering." They designed the Polycomb-based Transcription Factor (PcTF), a fusion protein that binds histone H3 trimethylated at K27. This feature (H3K27me3) is enriched at silenced tumor suppressors and other loci in cancer cells, therefore PcTF can be used to alleviate silencing at multiple genes and activate an anti-cancer gene expression profile. Powerful bioinformatics methods such as ChIP-seq and RNA-seq enable the discovery of genes that are controlled by PcTF. They are also building and testing more robust, re-engineered versions of PcTF using a cell-free expression platform.

Her group also develops new tools and produces general knowledge to support gene therapy-based applications. Chromatin often acts as a physical barrier against genome engineering efforts. They investigate how to manipulate chromatin at single chromosomal loci and on plasmid DNA to enhance transgene expression and gene editing. To observe nuclear uptake and chromatin states on plasmid DNA in live cells, they are developing fluorescence-based reporter systems. They have designed and tested fusion proteins to induce a sustained active state at epigenetically silenced genes. They are also investigating how these fusions can be used to enhance DNA-accessibility for CRISPR/Cas9-mediated gene editing in mammalian cells.