Description of Research Expertise

The Heller Lab studies the mechanisms by which epigenome remodeling regulates neuronal gene function and behavior. To approach this problem, we directly manipulate histone and DNA modifications at specific genes in vivo, using viral delivery of novel epigenetic editing tools, such as zinc-finger transcription factors and CRISPR/dCas9-fusion proteins. We use high-throughput sequencing to identify genes at which drug- or stress-regulation of a known epigenomic signature correlates with changes in expression. We can then target individual modifications and examine their causal relevance to transcriptional regulation and subsequent behavioral adaptations. This ‘bottom-up’ approach allows direct elucidation of the causal relevance of epigenetic remodeling in the brain. Because addiction and depression persist long after cessation of the harmful experience, epigenetic remodeling is an attractive underlying mechanism and presents an intriguing target for therapeutic intervention.