Elizabeth A Heller, PhD

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Associate Professor of Pharmacology
Department: Systems Pharmacology and Translational Therapeutics

Contact information
Department of Systems Pharmacology and Translational Therapeutics
Institute for Translational Medicine and Therapeutics
10-115 Smilow Center for Translational Research
3400 Civic Center Boulevard, Building 421
Philadelphia, PA 19104
Office: 215 573-7038
Stuyvesant High School, 1998.
BA (magna cum laude, Biology)
University of Pennsylvania, 2002.
PhD (Molecular Biology)
The Rockefeller University, 2009.
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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.

Selected Publications

Carpenter MD, Hu Q, Bond AM, Lombroso SI, Czarnecki KS, Lim CJ, Hongjun S, Wimmer ME, Pierce RC, Heller EA: Nr4a1 suppresses cocaine-induced behavior via epigenetic regulation of homeostatic target genes. Nat Commun. 11(504), January 2020.

Xu XJ, Lombroso SI, Fisher DK, Carpenter MD, Marchione DM, Hamilton PJ, Lim CJ, Neve RL, Garcia BA, Wimmer ME, Pierce RC, Heller EA: Chromatin-mediated alternative splicing regulates cocaine reward behavior. Neuron 109(18): 2943-2966, Sept 2021 Notes: Article Previewed in Bali & Kenny, Gene splicing SETs the scene for cocaine addiction, Neuron 2021.

Mews P, Egervari G, Nativio R, Sidoli S, Donahue G, Lombroso SI, Alexander DC, Riesche SL, Heller EA, Nestler EJ, Garcia BA, Berger SL: Alcohol metabolism contributes to brain histone acetylation. Nature 574(7780): 717-721, October 2019 Notes: Sonia Lombroso and Dr. Heller contributed all behavioral experimental design, execution, analysis and reported data to this manuscript, while at PSOM. Dr. Nestler is Dr. Heller's postdoctoral advisor, but their contributions to this manuscript are completely independent.

Gajewski PA, Eagle AL, Williams ES, Manning CE, Lynch H, McCornack C, Maze I, Heller EA, and Robison AJ : Epigenetic regulation of hippocampal Fosb expression controls behavioral responses to cocaine. J Neurosci. 39(42): 8305-8314, October 2019.

Xu S, Heller EA: Recent advances in neuroepigenetic editing. Curr Opin in Neurobiol. 59, Dec 2019.

Sase Ajinkya N, Lombroso Sonia I, Santhumayor Brandon A, Wood Roslyn R, Lim Carissa, Neve RL, Heller Elizabeth A: Sex-specific regulation of fear memory by targeted epigenetic editing of Cdk5. Biol Psychiatry 85(8): 623-634, April 2019.

Xu SJ, Heller EA: Single sample sequencing (S3EQ) of epigenome and transcriptome in nucleus accumbens. J Neurosci Methods 308: 62-73, Jul 2018.

Pierce R, Fant B, Swinford-Jackson S, Heller E, Berrettini W, Wimmer M: Environmental, genetic and epigenetic contributions to cocaine addiction. Neuropsychopharmacology 43(7): 1471-1480, June 2018.

Hu Q, Kim EJ, Feng J, Grant GR, Heller EA: Histone posttranslational modifications predict specific alternative exon subtypes in mammalian brain. PLoS Comput Biol. 13(6): e1005602, Jun 2017.

Heller EA, Cates HM, Peña CJ, Sun H, Shao N, Feng J, Golden SA, Herman JP, Walsh JJ, Mazei-Robison M, Ferguson D, Knight S, Gerber MA, Nievera C, Han MH, Russo SJ, Tamminga CS, Neve RL, Shen L, Zhang HS, Zhang F, Nestler EJ: Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors. Nat Neurosci. 17(12): 1720-7, Dec 2014.

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Last updated: 06/24/2024
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