Elizabeth A Heller

faculty photo
Assistant Professor of Pharmacology
Department: Pharmacology

Contact information
Laboratory of Neuroepigenetics
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
Education:
Diploma
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 Itmat 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.

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

Cates HM, Heller EA, Lardner CK, Purushothaman I, Peña CJ, Walker DM, Cahill ME, Neve RL, Shen L, Bagot RC, Nestler EJ.: Transcription Factor E2F3a in Nucleus Accumbens Affects Cocaine Action via Transcription and Alternative Splicing. Biol Psychiatry 84(3): 167-179, Aug 2018.

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 Notes: doi: 10.1038/s41386-018-0008-x.

Aleyasin H, Flanigan ME, Golden SA, Takahashi A, Menard C, Pfau ML, Multer J, Pina J, McCabe KA, Bhatti N, Hodes GE, Heshmati M, Neve RL, Nestler EJ, Heller EA, Russo SJ. : Cell-Type-Specific Role of ΔFosB in Nucleus Accumbens In Modulating Intermale Aggression. J Neuroscience 38(26): 5913-5924, Jun 2018.

Hamilton PJ, Burek DJ, Lombroso SI, Neve RL, Robison AJ, Nestler EJ, Heller EA: Cell-Type-Specific Epigenetic Editing at the Fosb Gene Controls Susceptibility to Social Defeat Stress. Neuropsychopharmacology 43(2): 272-284, Jan 2018.

Hamilton PJ, Lim CJ, Nestler EJ, Heller EA.: Viral Expression of Epigenome Editing Tools in Rodent Brain Using Stereotaxic Surgery Techniques. Methods Mol Biol. Rots MG & Jeltsch A (eds.). 1767: 205-214, 2018.

Sase AN, Lombroso SI, Santhumayor BS, Heller EA: Sex-specific regulation of fear memory by targeted epigenetic editing of Cdk5. Under Revision, Biol Psychiatry. 2018.

Hu Q, Greene CS, Heller EA: Specific histone modifications associate with alternative exon selection during mammalian development. Under Review, Nucleic Acids Research 2018.

Hamilton PJ, Lim CJ, Nestler EJ, Heller EA.: Neuroepigenetic editing. Methods Mol Biol. Rots MG & Jeltsch A (eds.). 1767: 205-214, 2018.

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

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Last updated: 08/22/2018
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