Department of Biological Science

Biological Science Faculty Member

Neuro Home Page

Associate Professor
PhD & Postdoc: UCLA 2009; Postdoc: Mount Sinai School of Medicine 2015
Graduate Faculty Status

Research and Professional Interests:

Epigenetic regulation of neuropsychiatric disorders.

Brain function requires accurate control of gene transcription in response to environmental stimuli. Epigenetics plays a key role during this process by modulating gene expression without changing underlying DNA sequences. It has therefore been implicated in various neuropsychiatric disorders, in which environmental factors contribute significantly to the pathgenesis. With help of modern genomic tools and novel epigenetic concepts largely developed in proliferating cultured cells, our laboratory aims to decipher out the epigenetic underpinnings of neuropsychiatric diseases in vivo by using rodent models.

We are currently persuing two major researches in drug addiction. 1) Three dimensional chromosome architecture in drug addiction. The compaction and organization of the linear DNA into the nucleus has been demonstrated to have a major influence on gene transcription by facilitating interactions between gene promoters and distal regulatory elements. To elucidate the uncharacterized three-dimensional chromatin architecture in drug addiction, we propose to study the long-range looping interactions between distal DNA elements and gene promoters within the specific neuronal subtypes differentially engaged in addiction. Our study will therefore provide novel insights into the transcriptional regulation underlying drug addiction. This research is currently supported by a NIDA Avenir Award.  2) Neuron subtype specific role of DNA methylcytosine dioxygenase TET1 in cocaine addiction. We propose to study the DNA epigenetic mechanism in drug addiction with a focus on TET1, a newly discovered methylated DNA dioxygenase that leads to DNA demethylation. We plan to elucidate the behavioral role of TET1 and its mediated DNA methylation turnover in the two major neuronal subtypes of the ventral striatum, the center of the brain reward pathway. Our study will not only elucidate a novel molecular mechanism of drug addiction within specific neuron types that are differentially engaged in drug addiction-like behavior, but may also provide a plausible path for therapeutic manipulation of addiction through DNA methylation perturbation.  This research is currently supported by a NIDA R01 fund.

Moreover, we are pursuing additional studies to expand our understanding of epigenetic underpinnings of neuropsychiatric disorders, some are through collaborations with other laboratories. With the integration of cutting-edge epigenetic/genomic tools and behavioral neuroscience, we aim to study biologically significant questions across a broader range of neuropsychiatric disorders.

Selected Publications:

Waddell NJ, Liu Y, Chitaman JM, Kaplan GJ, Wang Z#, Feng J#. (2023) Transcription and DNA methylation signatures of paternal care in hippocampal dentate gyrus of prairie voles. Scientific Reports (https://doi.org/10.1038/s41598-023-37521-2)

Li Y, Xu H, Chitaman JM, Feng J. (2022) Whole Genome DNA Methylation Profiling of D2 Medium Spiny Neurons in Mouse Nucleus Accumbens Using Two Independent Library Preparation Methods. Genes (Basel). (https://www.mdpi.com/resolver?pii=genes13020306). 

Kaplan G, Xu H, Abreu K, Feng J. (2022) DNA Epigenetics in Addiction Susceptibility. Front Genet. (https://doi.org/10.3389/fgene.2022.806685)

Wei  J, Cheng  J, Waddell NJ, Wang Z, Pang X, Cao Q, Aiyi Liu A, Chitaman JM, Abreu K, Jasrotia RS, Duffney LJ, Zhang J, Dietz DM, Feng J#, Yan Z#.(2021) DNA Methyltransferase 3A Is Involved in the Sustained Effects of Chronic Stress on Synaptic Functions and Behaviors. Cereb Cortex. 31(4):1998-2012.

Xu H, Brown AN, Waddell NJ, Liu X, Kaplan GJ, Chitaman JM, Stockman V, Hedinger RL, Adams R, Abreu K, Shen L, Neve R, Wang Z, Nestler EJ, Feng J. (2020) Role of long non-coding RNA Gas5 in cocaine action. Biological Psychiatry 88(10):758-766.

Chitaman JM, Fraser P, Feng J. (2019) Three-dimensional chromosome architecture and drug addiction. Current Opinion in Neurobiology (59): 137-145.

Walker D, Cates H, Loh Y, Purushothaman I, Ramakrishnan A, Cahill K, Lardner C, Godino A, Kronman H, Rabkin J, Lorsch Z, Mews P, Doyle M, Feng J, Labonte B, Koo J, Bagot R, Callipari E, Shen L, Nestler EJ. (2018) Cocaine Self-administration Alters Transcriptome-wide Responses in the Brain's Reward Circuitry. Biological Psychiatry, 84, 867-880.

Brown AN, Feng J. (2017) Drug Addiction and DNA Modifications. Adv Exp Med Biol, 978, 105-125.

Feng J. (2017) Role of Cyfip2 in binge eating. Biological Psychiatry, 81(9), e77-e78.

Feng J, Pena CJ, Purushothaman I, Engmann O, Walker D, Brown AN, Issler O, Doyle M, Harrigan E, Mouzon E, Vialou V, Shen L, Dawlaty MM, Jaenisch R, Nestler EJ. (2017) Tet1 in nucleus accumbens opposes depression and anxiety-like behaviors. Neuropsychopharmacology, 42(8), 1657-1669.

Hu Q, Kim EJ, Feng J, Grant GR, Heller EA. (2017) Histone Posttranslational Modifications Predict Specific Alternative Exon Subtypes in Mammalian Brain. PLoS Comput Biol, 13(6), e1005602.

Loh YE, Feng J, Nestler EJ, Shen L. (2017) Bioinformatic Analysis for Profiling Drug-induced Chromatin Modification Landscapes in Mouse Brain Using ChlP-seq Data. Bio Protoc, 7(3), 19.

Natt D, Barchiesi R, Murad J, Feng J, Nestler EJ, Champagne FA, Thorsell A. (2017) Perinatal Malnutrition Leads to Sexually Dimorphic Behavioral Responses with Associated Epigenetic Changes in the Mouse Brain. Scientific Reports, 7(1), 11082

Zhao JY, Liang L, Gu X, Li Z, Wu S, Sun L, Atianjoh FE, Feng J, Mo K, Jia S, Lutz BM, Bekker A, Nestler EJ, Tao YX. (2017)  DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons. Nature  Communications, 8, 14712. 

Sun L, Zhao JY, Gu X, Liang L, Wu S, Mo K, Feng J, Guo W, Zhang J, Bekker A, Zhao X, Nestler EJ, Tao YX. (2017) Nerve Injury-Induced Epigenetic Silencing Of Opioid Receptors Controlled By Dnmt3a In Primary Afferent Neurons. Pain, 158(6), 1153-1165.

Pfau ML, Purushothaman I, Feng J, Golden SA, Aleyasin H, Lorsch ZS, Cates HA, Flanigan ME, Menard C, Heshmati M, Wang Z, Ma’ayan A, Shen L, Hodes GE, Russo SJ. (2016). Intergrative Aanalysis of Sex-Sepcific microRNA Networks Following Stress in Mouse Nucleus Accumbens. Frontiers in Molecular Neuroscience, 9, 144.

Wang T, Santos JH, Feng J, Fargo DC, Shen L, Riadi G, Keeley E, Rosh ZS, Nestler EJ, Woychik RP. (2016). A Novel Analytical Strategy to Identify Fusion Transcripts between Repetitive Elements and Protein Coding-Exons Using RNA-Seq. PLOS One. 11(7):e0159028.

Cahill ME, Bagot RC, Gancarz AM, Walker DM, Sun H, Wang ZJ, Heller EA, Feng J Kennedy PJ, Koo JW, Cates HM, Neve RL, Shen L, Dietz DM, Nestler EJ. (2016). Bidirectional Synaptic Structural Plasticity after Chronic Cocaine Administration Occurs through Rap1 Small GTPase Signaling. Neuron. 89(3):566-82.

Mitsi V, Terzi D, Puruphashaman I, Manouras L, Gaspari S, Stratinaki M, Feng J, Shen L, Zachariou V. (2015) RGS9-2 actions in the nucleus accumbens modulate the antiallodynic and antidepressant actions of tricyclic antidepressants in models of neuropathic pain. PNAS. 112(36):E5088-97. 

Hodes GE, Pfau ML, Purushothaman I, Ahn HF, Golden SA, Christoffel DJ, Aleyasin H, Koo JW, Lorsch Z, Feng J Heshmati M, Turecki G, Neve R, Shen L, Nestler EJ, Russo SJ. (2015) Sex differences in nucleus accumbens transcriptome profiles associated with susceptibility versus resilience to sub-chronic variable stress. Journal of Neuroscience. 35(50):16362-76.

Wright KN, Hollis F, Duclot F, Dossat AM, Strong CE, Francis TC, Mercer R, Feng J, Dietz DM, Lobo MK, Nestler EJ, Kabbaj M. (2015) Methyl supplementation attenuates cocaine-seeking behaviors and cocaine-induced c-fos activation in a DNA methylation-dependent manner. Journal of Neuroscience. 10; 35(23):8948-58.

Feng J, Shao N, Szulwach KE, Vialou V, Huynh J, Zhong C, Le T, Li Y, Ferguson D, Cahill ME, Koo JW, Laitman B, Estey D, Stockman V, Ribeiro E, Kennedy P, Mensah I, Turecki G, Faull KF, Song H, Fan G, Casaccia P, Shen L, Jin P, Nestler EJ. (2015) Role of Tet1 and 5-hydroxymethylcytosine in cocaine action. Nature Neuroscience. 18(4):536-44.

Ferguson D, Shao N, Heller EA, Feng J, Neve R, Shen L, Nestler EJ. (2015) SIRT1-FOXO3a regulate cocaine actions in the nucleus accumbens. Journal of Neuroscience. 18;35(7):3100-11

Koo JW, Mazei-Robison MS, LaPlant Q, Egervari G, Braunscheide KM, Adank DN, Ferguson D, Feng J, Sun H, Scobie KN, Damez-Werno DM, Ribeiro E, Peña CJ, Walker D, Bagot RC, Cahill ME, Anderson SAR, Labonté B, Hodes GE, Browne H, Chadwick B, Robison AJ, Vialou VF, Dias C, Lorsch Z, Mouzon E, Lobo MK, Dietz DM, Russo SJ, Neve RL, Hurd YL, Nestler EJ. (2014) Epigenetic basis of opiate suppression of Bdnf gene expression in the ventral tegmental area. Natture Neuroscience. 18(3):415-22.

Dias C*, Feng J*, Sun H, Shao NY, Mazei-Robison MS, Damez-Werno D, Scobie K, Bagot R, LaBonté B, Ribeiro E, Liu X, Kennedy P, Vialou V, Ferguson D, Peña C, Calipari ES, Koo JW, Mouzon E, Ghose S, Tamminga C, Neve R, Shen L#, Nestler EJ#. (2014) β-Catenin mediated stress resilience through Dicer1/microRNA regulation. Nature. Dec 4;516(7529):51-5.  (* equal contribution)

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

Feng J, Wilkinson M, Liu X, Purushothaman I, Ferguson D, Vialou V, Maze I, Shao N, Kennedy P, Koo JW, Dias C, Laitman B, Stockman V, LaPlant L, Cahill M, Nestler EJ#, Shen L#. (2014) Chronic cocaine-regulated epigenomic chages in mouse nucleus accumbens. Genome Biology. 15(4):R65  

Vialou V, Bagot R, Cahill M, Ferguson D, Robison A, Ku S, Dietz D, Fallon B, Mazei-Robison M, Harrigan E, Winstanley C, Joshi T, Feng J, Berton O, Nestler EJ. (2014) Prefrontal cortical circuit for depression- and anxiety-related behaviors mediated by cholecystokinin: Role of ΔFosB. Journal of Neuroscience 34(11):3878-87

Ferguson D, Koo JW, Feng J, Heller E, Rabkin J, Heshmati M, Renthal W, Neve R, Liu X, Shao N, Sartorelli V, Shen L, Nestler EJ. (2013). Essential Role of SIRT1 Signaling in the Nucleus Accumbens in Cocaine and Morphine Action. Journal of Neuroscience. 33(41):16088-16098.

Shen L, Shao NY, Liu X, Maze I, Feng J, Nestler EJ. (2013). diffReps: detecting differential chromatin modification sites from ChIP-seq data with biological replicates. PLOS One. 8(6):e65598.

Kennedy PJ, Feng J, Robison AJ, Maze I, Badimon A, Mouzon E, Chaudhury D, Damez-Werno DM, Haggarty SJ, Han MH, Bassel-Duby R, Olson EN, Nestler EJ. (2013). Class I HDAC inhibition blocks cocaine-induced plasticity through targeted changes in histone methylation. Nature Neuroscience. 16(4):434-40.

Robison AJ, Vialou V, Mazei-Robison M, Feng J, Kourrich S, Collins M, Wee S, Koob G, Turecki G, Neve R, Thomas M, Nestler EJ. (2013). Behavioral and Structural Responses to Chronic Cocaine Require a Feed-Forward Loop Involving ΔFosB and CaMKII in the Nucleus Accumbens Shell. Journal of Neuroscience. 33(10):4295-307.

Feng J, Nestler EJ. (2013). Epigenetic mechanisms of drug addiction. Current Opinion in Neurobiology. 23(4):521-8. (Review)

Koo JW, Mazei-Robison MS, Chaudhury D, Juarez B, LaPlant Q, Ferguson D, Feng J, Sun H, Scobie KN, Damez-Werno D, Crumiller M, Ohnishi YN, Ohnishi YH, Mouzon E, Dietz DM, Lobo MK, Neve RL, Russo SJ, Han MH, Nestler EJ. (2012). BDNF is a negative modulator of morphine action. Science. 5;338(6103):124-8.

Vialou V, Feng J, Robison AJ, Nestler EJ. (2013). Epigenetic mechanisms of depression and antidepressant action. Annual Review of Pharmacology and Toxicology. 6;53:59-87. (Review)

Warren BL, Vialou VF, Iñiguez SD, Alcantara LF, Wright KN, Feng J, Kennedy PJ, Laplant Q, Shen L, Nestler EJ, Bolaños-Guzmán CA. (2013). Neurobiological sequelae of witnessing stressful events in adult mice. Biological Psychiatry. 73(1):7-14.

Vialou V*, Feng J*, Robison AJ, Ku SM, Ferguson D, Scobie KN, Mazei-Robison MS, Mouzon E, Nestler EJ. (2012). Serum response factor and cAMP response element binding protein are both required for cocaine induction of ΔFosB. Journal of Neuroscience. 32(22):7577-84. (* equal contribution)

Dietz DM, Laplant Q, Watts EL, Hodes GE, Russo SJ, Feng J, Oosting RS, Vialou V, Nestler EJ. (2011). Paternal transmission of stress-induced pathologies. Biological Psychiatry. 70(5):408-14.

Maze I, Feng J, Wilkinson MB, Sun H, Shen L, Nestler EJ. (2011). Cocaine dynamically regulates heterochromatin and repetitive element unsilencing in nucleus accumbens. Proceedings of the National Academy of Sciences. 108(7):3035-40.

Gomez-Pinilla F, Zhuang Y, Feng J, Ying Z, Fan G. (2011). Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation. European Journal of Neuroscience. 33(3):383-90.

Feng J, Nestler EJ. (2010). MeCP2 and drug addiction. Nature Neuroscience. 13(9):1039-41. (News and Views)

LaPlant Q, Vialou V, Covington HE 3rd, Dumitriu D, Feng J Warren BL, Maze I, Dietz DM, Watts EL, Iñiguez SD, Koo JW, Mouzon E, Renthal W, Hollis F, Wang H, Noonan MA, Ren Y, Eisch AJ, Bolaños CA, Kabbaj M, Xiao G, Neve RL, Hurd YL, Oosting RS, Fan G, Morrison JH, Nestler EJ. (2010). Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens. Nature Neuroscience. 13(9):1137-43.

Feng J, Zhou Y, Campbell SL, Le T, Li E, Sweatt JD, Silva AJ, Fan G. (2010). Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons. Nature Neuroscience. 13(4):423-30.

Feng J, Fan G. (2009). The role of DNA methylation in the central nervous system and neuropsychiatric disorders. International Review of Neurobiology. 89:67-84. (Review)

Feng J, Fouse S, Fan G. (2007). Epigenetic regulation of neural gene expression and neuronal function. Pediatric Research. 61(5 Pt 2):58R-63R. (Review)

Feng J, Chang H, Li E, Fan G. (2005). Dynamic expression of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the central nervous system. Journal of Neuroscience Research. 79(6):734-46.

Postdoctoral Associates:

Graduate Students: