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
Graduate Group Affiliations
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

Hu Qiwen, Kim Eun Ji, Feng Jian, Grant Gregory R, Heller Elizabeth A: Histone posttranslational modifications predict specific alternative exon subtypes in mammalian brain. PLoS computational biology 13(6): e1005602, Jun 2017.

Lopez Juan Pablo, Fiori Laura M, Cruceanu Cristiana, Lin Rixing, Labonte Benoit, Cates Hannah M, Heller Elizabeth A, Vialou Vincent, Ku Stacy M, Gerald Christophe, Han Ming-Hu, Foster Jane, Frey Benicio N, Soares Claudio N, Müller Daniel J, Farzan Faranak, Leri Francesco, MacQueen Glenda M, Feilotter Harriet, Tyryshkin Kathrin, Evans Kenneth R, Giacobbe Peter, Blier Pierre, Lam Raymond W, Milev Roumen, Parikh Sagar V, Rotzinger Susan, Strother Steven C, Lewis Cathryn M, Aitchison Katherine J, Wittenberg Gayle M, Mechawar Naguib, Nestler Eric J, Uher Rudolf, Kennedy Sidney H, Turecki Gustavo: MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes. Nature communications 8: 15497, May 2017.

Hamilton Peter J, Burek Dominika J, Lombroso Sonia I, Neve Rachael L, Robison Alfred J, Nestler Eric J, Heller Elizabeth A: Cell-Type-Specific Epigenetic Editing at the Fosb Gene Controls Susceptibility to Social Defeat Stress. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology May 2017.

Bagot Rosemary C, Cates Hannah M, Purushothaman Immanuel, Vialou Vincent, Heller Elizabeth A, Yieh Lynn, LaBonté Benoit, Peña Catherine J, Shen Li, Wittenberg Gayle M, Nestler Eric J: Ketamine and Imipramine Reverse Transcriptional Signatures of Susceptibility and Induce Resilience-Specific Gene Expression Profiles. Biological psychiatry 81(4): 285-295, Feb 2017.

Bagot Rosemary C, Cates Hannah M, Purushothaman Immanuel, Lorsch Zachary S, Walker Deena M, Wang Junshi, Huang Xiaojie, Schlüter Oliver M, Maze Ian, Peña Catherine J, Heller Elizabeth A, Issler Orna, Wang Minghui, Song Won-Min, Stein Jason L, Liu Xiaochuan, Doyle Marie A, Scobie Kimberly N, Sun Hao Sheng, Neve Rachael L, Geschwind Daniel, Dong Yan, Shen Li, Zhang Bin, Nestler Eric J: Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility. Neuron May 2016.

Heller Elizabeth A, Hamilton Peter J, Burek Dominika D, Lombroso Sonia I, Peña Catherine J, Neve Rachael L, Nestler Eric J: Targeted Epigenetic Remodeling of the Cdk5 Gene in Nucleus Accumbens Regulates Cocaine- and Stress-Evoked Behavior. The Journal of neuroscience : the official journal of the Society for Neuroscience 36(17): 4690-7, Apr 2016.

Cahill Michael E, Bagot Rosemary C, Gancarz Amy M, Walker Deena M, Sun HaoSheng, Wang Zi-Jun, Heller Elizabeth A, Feng Jian, Kennedy Pamela J, Koo Ja Wook, Cates Hannah M, Neve Rachael L, Shen Li, Dietz David M, Nestler Eric J: Bidirectional Synaptic Structural Plasticity after Chronic Cocaine Administration Occurs through Rap1 Small GTPase Signaling. Neuron 89(3): 566-82, Feb 2016.

Sun HaoSheng, Damez-Werno Diane M, Scobie Kimberly N, Shao Ning-Yi, Dias Caroline, Rabkin Jacqui, Koo Ja Wook, Korb Erica, Bagot Rosemary C, Ahn Francisca H, Cahill Michael E, Labonté Benoit, Mouzon Ezekiell, Heller Elizabeth A, Cates Hannah, Golden Sam A, Gleason Kelly, Russo Scott J, Andrews Simon, Neve Rachael, Kennedy Pamela J, Maze Ian, Dietz David M, Allis C David, Turecki Gustavo, Varga-Weisz Patrick, Tamminga Carol, Shen Li, Nestler Eric J: ACF chromatin-remodeling complex mediates stress-induced depressive-like behavior. Nature medicine 21(10): 1146-53, Oct 2015.

Ferguson Deveroux, Shao Ningyi, Heller Elizabeth, Feng Jian, Neve Rachael, Kim Hee-Dae, Call Tanessa, Magazu Samantha, Shen Li, Nestler Eric J: SIRT1-FOXO3a regulate cocaine actions in the nucleus accumbens. The Journal of neuroscience 35(7): 3100-11, Feb 2015.

Walker Deena M, Cates Hannah M, Heller Elizabeth A, Nestler Eric J: Regulation of chromatin states by drugs of abuse. Current opinion in neurobiology 30: 112-21, Feb 2015.

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Last updated: 11/29/2017
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