Maze Lab

Laboratory of Mechanistic Neuroepigenetics and Disease

Research

ian mazeThe Maze laboratory is focused on understanding the complex interplay between chromatin regulatory mechanisms in brain and neuronal plasticity. We combine a wide variety of biochemical, biophysical, molecular and behavioral approaches to assess the role of histone proteins, and their associated posttranslational modifications, turnover dynamics and remodeling activities, in the regulation of normal neurodevelopment, and the contribution of such processes, or aberrations thereof, to neurological and psychiatric disease. We place particular emphasis on psychiatric disorders associated with monoaminergic (e.g., serotonin, dopamine, etc.) dysfunction, such as major depressive disorder and drug addiction, as well as neurodevelopmental syndromes resulting in deficits in synaptic plasticity and intellectual disability (e.g., Down syndrome and autism). Being both ‘basic’ and translational in nature, our work – so-called “mechanistic neuroepigenetics” – employs state-of-the-art gene and chromatin arraying technologies, analytical chemistry (e.g., mass spectrometry and 14C bomb pulse labeling) and neurobiological phenotyping, in both rodents and humans (postmortem brain and iPSC derived neurons), to explore novel chromatin phenomena in the central nervous system. This includes the identification and characterization of neuronally enriched histone modifications, chromatin “readers,” “writers” and “erasers,” all of which play critical roles in neuronal plasticity and behavioral adaptation.NIMH NID logos

Projects

Our research is centered on understanding neuroepigenetic mechanisms responsible for transcriptional and synaptic plasticity in the central nervous system. Our work represents a unique blend of chromatin biochemistry, chemical biology and functional neurobiology to address fundamental questions related to the molecular underpinnings of neurodevelopmental disorders and adult psychiatric illness.
acculumulation h3 variant brain tissue diagram
Examples of current projects in the lab include:

  1. Functional dissection of regulatory roles for histone turnover versus nucleosomal remodeling in the mediation of activity-dependent gene transcription in neurons.
  2. The role of nucleosomal turnover in corticostriatal limbic circuitry in the regulation of depressive-like behaviors in both rodents and humans.
  3. Combinatorial histone posttranslational modification profiling and genome-wide chromatin analyses to investigate developmental trajectories of human psychiatric illness (e.g., schizophrenia – in collaboration with Dr. Kristen Brennand).
  4. Biochemical and functional characterization of novel neuronally enriched histone modification states in the central nervous system (relationships to major depressive disorder, drug addiction, etc.).
  5. Identification and characterization of neuronal specific histone “reader” proteins, and their respective roles in neurodevelopmental plasticity and disease (e.g., Down syndrome associated intellectual disability).
  6. Development of novel epigenomic editing tools to disrupt or potentiate histone modification states in brain.

Contact Us

Maze Laboratory
Ian Maze, PhD
Professor, Neuroscience
Professor, Pharmacological Sciences
Location
Lab: HESS CSM 9-201
Office: HESS CSM 9-109
Phone
Office: 212.824.8979
Lab: 212.996.7214
Email

Publications

2016

Aberrant H3.3 dynamics in NAc promote vulnerability to depressive-like behavior.
Lepack AE, Bagot RC, Peña CJ, Loh YE, Farrelly LA, Lu Y, Powell SK, Lorsch ZS, Issler O, Cates HM, Tamminga CA, Molina H, Shen L, Nestler EJ, Allis CD, Maze I.
Proc Natl Acad Sci U S A. 2016 Nov 1;113(44):12562-12567.


Histone arginine methylation in cocaine action in the nucleus accumbens.
Damez-Werno DM, Sun H, Scobie KN, Shao N, Rabkin J, Dias C, Calipari ES, Maze I, Pena CJ, Walker DM, Cahill ME, Chandra R, Gancarz A, Mouzon E, Landry JA, Cates H, Lobo MK, Dietz D, Allis CD, Guccione E, Turecki G, Defilippi P, Neve RL, Hurd YL, Shen L, Nestler EJ.
Proc Natl Acad Sci U S A. 2016 Aug 23;113(34):9623-8. doi: 10.1073/pnas.1605045113. Epub 2016 Aug 9.


Current Proteomic Methods to Investigate the Dynamics of Histone Turnover in the Central Nervous System.
Farrelly LA, Dill BD, Molina H, Birtwistle MR, Maze I.
Methods Enzymol. 2016;574:331-54. doi: 10.1016/bs.mie.2016.01.013. Epub 2016 Feb 16.


Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility.
Bagot RC, Cates HM, Purushothaman I, Lorsch ZS, Walker DM, Wang J, Huang X, Schlüter OM, Maze I, Peña CJ, Heller EA, Issler O, Wang M, Song WM, Stein JL, Liu X, Doyle MA, Scobie KN, Sun HS, Neve RL, Geschwind D, Dong Y, Shen L, Zhang B, Nestler EJ.
Neuron. 2016 Jun 1;90(5):969-83. doi: 10.1016/j.neuron.2016.04.015. Epub 2016 May 12.


Histone turnover and chromatin accessibility: Critical mediators of neurological development, plasticity, and disease.
Wenderski W, Maze I.
Bioessays. 2016 May;38(5):410-9. doi: 10.1002/bies.201500171. Epub 2016 Mar 15.

2015

ACF chromatin-remodeling complex mediates stress-induced depressive-like behavior.
Sun H, Damez-Werno DM, Scobie KN, Shao NY, Dias C, Rabkin J, Koo JW, Korb E, Bagot RC, Ahn FH, Cahill ME, Labonté B, Mouzon E, Heller EA, Cates H, Golden SA, Gleason K, Russo SJ, Andrews S, Neve R, Kennedy PJ, Maze I, Dietz DM, Allis CD, Turecki G, Varga-Weisz P, Tamminga C, Shen L, Nestler EJ.Nature Medicine. 2015 Oct;21(10):1146-53. doi: 10.1038/nm.3939. Epub 2015 Sep 21.


Critical role of histone turnover in neuronal transcription and plasticity
Maze I, Wenderski W, Noh KM, Bagot R, Tzavaras N, Purushothaman I, Elsässer S, Guo Y, Ionete C, Hurd Y, Tamminga C, Halene T, Farrelly L, Soshnev A, Wen D, Rafii S, Birtwistle M, Akbarian S, Buchholz B, Blitzer R, Nestler E, Yuan ZF, Garcia B, Shen L, Molina H, Allis CD
Neuron. 2015 Jul 1;87(1):77-94. doi: 10.1016/j.neuron.2015.06.014.


Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression.
Bagot RC, Parise EM, Peña CJ, Zhang HX, Maze I, Chaudhury D, Persaud B, Cachope R, Bolaños-Guzmán CA, Cheer J, Deisseroth K, Han MH, Nestler EJ.
Nature Communications. 2015 May 8;6:7062. doi: 10.1038/ncomms8062.


Antidepressant action of HDAC inhibition in the prefrontal cortex.
Covington HE 3rd, Maze I, Vialou V, Nestler EJ.
Neuroscience. 2015 Jul 9;298:329-35. doi: 10.1016/j.neuroscience.2015.04.030. Epub 2015 Apr 20.


ATRX tolerates activity-dependent histone H3 methyl/phos switching to maintain repetitive element silencing in neurons.
Noh KM, Maze I, Zhao D, Xiang B, Wenderski W, Lewis PW, Shen L, Li H, Allis CD.
Proceedings of the National Academy of Sciences. 2015 Jun 2;112(22):6820-7. doi: 10.1073/pnas.1411258112. Epub 2014 Dec 23.

2014

Analytical tools and current challenges in the modern era of neuroepigenomics.
Maze I, Shen L, Zhang B, Garcia BA, Shao N, Mitchell A, Sun H, Akbarian S, Allis CD, Nestler EJ.
Nature Neuroscience. 2014 Nov;17(11):1476-90. doi: 10.1038/nn.3816. Epub 2014 Oct 28. Review.


Chronic cocaine-regulated epigenomic changes in mouse nucleus accumbens. 
Feng J, Wilkinson M, Liu X, Purushothaman I, Ferguson D, Vialou V, Maze I, Shao N, Kennedy P, Koo J, Dias C, Laitman B, Stockman V, LaPlant Q, Cahill ME, Nestler EJ, Shen L.
Genome Biology 2014 April 22; 15(4).


Every amino acid matters: essential contributions of histone variants to mammalian development and disease.
Maze I, Noh KM, Soshnev AA, Allis CD.
Nature Reviews. Genetics 2014 Apr; 15(4).


G9a influences neuronal subtype specification in striatum.
Maze I, Chaudhury D, Dietz DM, Von Schimmelmann M, Kennedy PJ, Lobo MK, Sillivan SE, Miller ML, Bagot RC, Sun H, Turecki G, Neve RL, Hurd YL, Shen L, Han MH, Schaefer A, Nestler EJ.
Nature Neuroscience 2014 Apr; 17(4).


ΔFosB induction in prefrontal cortex by antipsychotic drugs is associated with negative behavioral outcomes.
Dietz DM, Kennedy PJ, Sun H, Maze I, Gancarz AM, Vialou V, Koo JW, Mouzon E, Ghose S, Tamminga CA, Nestler EJ.
Neuropsychopharmacology 2014 Feb; 39(3).

2013

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


Class I HDAC inhibition blocks cocaine-induced plasticity by targeted changes in histone methylation.
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.
Nature Neuroscience 2013 Apr; 16(4).


Histone regulation in the CNS: basic principles of epigenetic plasticity.
Maze I, Noh KM, Allis CD.
Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology 2013 Jan; 38(1).

2012

Morphine epigenomically regulates behavior through alterations in histone H3 lysine 9 dimethylation in the nucleus accumbens.
Sun H, Maze I, Dietz DM, Scobie KN, Kennedy PJ, Damez-Werno D, Neve RL, Zachariou V, Shen L, Nestler EJ.
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience 2012 Nov; 32(48).


Rac1 is essential in cocaine-induced structural plasticity of nucleus accumbens neurons.
Dietz DM, Sun H, Lobo MK, Cahill ME, Chadwick B, Gao V, Koo JW, Mazei-Robison MS, Dias C, Maze I, Damez-Werno D, Dietz KC, Scobie KN, Ferguson D, Christoffel D, Ohnishi Y, Hodes GE, Zheng Y, Neve RL, Hahn KM, Russo SJ, Nestler EJ.
Nature Neuroscience 2012 Jun; 15(6).

2011 & earlier

2011

A role for repressive histone methylation in cocaine-induced vulnerability to stress.
Covington HE, Maze I, Sun H, Bomze HM, DeMaio KD, Wu EY, Dietz DM, Lobo MK, Ghose S, Mouzon E, Neve RL, Tamminga CA, Nestler EJ.
Neuron 2011 Aug; 71(4).


Behavioral epigenetics.
Lester BM, Tronick E, Nestler E, Abel T, Kosofsky B, Kuzawa CW, Marsit CJ, Maze I, Meaney MJ, Monteggia LM, Reul JM, Skuse DH, Sweatt JD, Wood MA.
Annals of the New York Academy of Sciences 2011 May; 1226.


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


The epigenetic landscape of addiction.
Maze I, Nestler EJ.
Annals of the New York Academy of Sciences 2011 Jan; 1216.

2010

Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex.
Covington HE, Lobo MK, Maze I, Vialou V, Hyman JM, Zaman S, LaPlant Q, Mouzon E, Ghose S, Tamminga CA, Neve RL, Deisseroth K, Nestler EJ.
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience 2010 Dec; 30(48).


Serum response factor promotes resilience to chronic social stress through the induction of DeltaFosB.
Vialou V, Maze I, Renthal W, LaPlant QC, Watts EL, Mouzon E, Ghose S, Tamminga CA, Nestler EJ.
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience 2010 Oct; 30(43).


Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens.LaPlant Q, Vialou V, Covington HE, 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.
Nature Neuroscience 2010 Sep; 13(9).


Transcriptional mechanisms: underlying addiction-related structural plasticity.
Maze I, Russo SJ.
Molecular Interventions 2010 Aug; 10(4).


Essential role of the histone methyltransferase G9a in cocaine-induced plasticity.
Maze I, Covington HE, Dietz DM, LaPlant Q, Renthal W, Russo SJ, Mechanic M, Mouzon E, Neve RL, Haggarty SJ, Ren Y, Sampath SC, Hurd YL, Greengard P, Tarakhovsky A, Schaefer A, Nestler EJ.
Science (New York, N.Y.) 2010 Jan; 327(5962).

2009

Antidepressant actions of histone deacetylase inhibitors.
Covington HE, Maze I, LaPlant QC, Vialou VF, Ohnishi YN, Berton O, Fass DM, Renthal W, Rush AJ, Wu EY, Ghose S, Krishnan V, Russo SJ, Tamminga C, Haggarty SJ, Nestler EJ.
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience 2009 Sep; 29(37).


Genome-wide analysis of chromatin regulation by cocaine reveals a role for sirtuins.
Renthal W, Kumar A, Xiao G, Wilkinson M, Covington HE, Maze I, Sikder D, Robison AJ, LaPlant Q, Dietz DM, Russo SJ, Vialou V, Chakravarty S, Kodadek TJ, Stack A, Kabbaj M, Nestler EJ.
Neuron 2009 May; 62(3).


Role of nuclear factor kappaB in ovarian hormone-mediated stress hypersensitivity in female mice.
LaPlant Q, Chakravarty S, Vialou V, Mukherjee S, Koo JW, Kalahasti G, Bradbury KR, Taylor SV, Maze I, Kumar A, Graham A, Birnbaum SG, Krishnan V, Truong HT, Neve RL, Nestler EJ, Russo SJ.
Biological Psychiatry 2009 May; 65(10).


Nuclear factor kappa B signaling regulates neuronal morphology and cocaine reward.
Russo SJ, Wilkinson MB, Mazei-Robison MS, Dietz DM, Maze I, Krishnan V, Renthal W, Graham A, Birnbaum SG, Green TA, Robison B, Lesselyong A, Perrotti LI, Bolaños CA, Kumar A, Clark MS, Neumaier JF, Neve RL, Bhakar AL, Barker PA, Nestler EJ.
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience 2009 Mar; 29(11).

2008

Delta FosB mediates epigenetic desensitization of the c-fos gene after chronic amphetamine exposure.
Renthal W, Carle TL, Maze I, Covington HE, Truong HT, Alibhai I, Kumar A, Montgomery RL, Olson EN, Nestler EJ.
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience 2008 Jul; 28(29).


Distinct patterns of DeltaFosB induction in brain by drugs of abuse.
Perrotti LI, Weaver RR, Robison B, Renthal W, Maze I, Yazdani S, Elmore RG, Knapp DJ, Selley DE, Martin BR, Sim-Selley L, Bachtell RK, Self DW, Nestler EJ.
Synapse (New York, N.Y.) 2008 May; 62(5).

2007

Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli.
Renthal W, Maze I, Krishnan V, Covington HE, Xiao G, Kumar A, Russo SJ, Graham A, Tsankova N, Kippin TE, Kerstetter KA, Neve RL, Haggarty SJ, McKinsey TA, Bassel-Duby R, Olson EN, Nestler EJ.
Neuron 2007 Nov; 56(3).


Acute ethanol ingestion produces dose-dependent effects on motor behavior in the honey bee (Apis mellifera).
Maze IS, Wright GA, Mustard JA.
Journal of Insect Physiology; 52(11-12).

Meet the Team

Lorna Farrelly, Ph.D.

Lorna Farrelly, Ph.D.

Postdoctoral Fellow

lorna.farrelly@mssm.edu

Sasha Fulton

Sasha Fulton

Sasha Fulton

sasha.fulton@icahn.mssm.edu

Ryan Bastle, Ph.D.

Ryan Bastle, Ph.D.

Postdoctoral Fellow

ryan.bastle@mssm.edu

Yang Lu

Yang Lu

Senior Associate Researcher

yang.lu@mssm.edu

Ashley Lepack

Ashley Lepack

PhD Candidate

Ashley.Lepack@icahn.mssm.edu

Amni Al-Kachak

Amni Al-Kachak

PhD Student

amni.al-kachak@icahn.mssm.edu

Awards

2017

Fay/Frank Seed Grant from the Brain Research Foundation

Dr. Maze is a recipient of the 2017 March of Dimes Basil O’Connor Starter Scholar Research Award funded by March of Dimes Foundation

2016

Dr. Maze is a recipient of the 2016 Sloan Research Fellowship in Neuroscience

Dr. Maze is a receipient of the 2016 Avenir Award funded by National Institute on Drug Abuse

Dr. Maze is supported, in part, by the Conte Translational Neuroscience Center on Depression funded by NIMH use

2015

Dr. Maze receives a 2015 Friedman Brain Institute Rosen Family Research Scholar Award

Dr. Maze receives a 2015 ACNP Travel Award

2014