Elizabeth is an Assistant Professor in the Pharmacology Department in Perelman School of Medicine, University of Pensylvania. Elizabeth is interested in environmental, genetic and epigenetic contributions to cocaine addiction.
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.
To carry out our investigations we analyze the epigenome of brain reward regions of rodents exposed to chronic drug and stress paradigms, including drug self-administration, which most closely models the human experience. Conversely, we utilize viral-delivery of highly novel molecular tools to manipulate the molecular motifs at a specific gene to determine their causal role in drug- and stress-responsive behaviors. Using this approach we aim to make great strides towards elucidating the precise functional relevance of epigenetic remodeling in neuropsychiatric disease.
For more information please visit http://www.med.upenn.edu/hellerlab/research.html