Schaefer Lab

Laboratory of Brain Epigenetics

Understanding Mechanism of Neurological Disorders

Research

anne schaeferOur research focuses on identifying the epigenetic basis of neurodegenerative and psychiatric disorders. We study how miRNAs and histone modifying enzymes contribute to the establishment and maintenance of neuronal identity and specialized functions. We are particularly interested in understanding the epigenetic mechanisms of cellular plasticity and its role in regulation of microglia-neuron communication. One of the major focuses of our research lies in the development of animal models of human neurological disease associated with abnormal function of epigenetic regulators of different types. Using pioneering technologies including cell type specific analysis of mRNAs, miRNAs and chromatin modifications in neurons in vivo, our research aims at understanding the mechanism of neurological disorders and at their potential treatment by targeting the neuronal epigenome.

Contact Us

Schaefer Laboratory
Anne Schaefer, MD, PhD
Associate Professor, Neuroscience
Associate Professor, Psychiatry
Location
Lab: ICAHN 10-76
Office: ICAHN 10-70A
Phone
Office: 212.659.5987
Lab: 212.659.5577
Email

Publications

2018

Epigenetic regulation of brain region-specific microglia clearance activity.

Ayata P, Badimon A, Strasburger HJ, Duff MK, Montgomery SE, Loh YE, Ebert A, Pimenova AA, Ramirez BR, Chan AT, Sullivan JM, Purushothaman I, Scarpa JR, Goate AM, Busslinger M, Shen L, Losic B, Schaefer A.

Nat Neurosci. 2018 Jul 23. doi: 10.1038/s41593-018-0192-3. [Epub ahead of print]

PMID: 30038282

Featured as news and views at Nature neuroscience: https://www.nature.com/articles/s41593-018-0196-z

2017

Jiang Y, Loh YE, Rajarajan P, Hirayama T, Liao W, Kassim BS, Javidfar B, Hartley BJ, Kleofas L, Park RB, Labonte B, Ho SM, Chandrasekaran S, Do C, Ramirez BR, Peter CJ, C W JT, Safaie BM, Morishita H, Roussos P, Nestler EJ, Schaefer A, Tycko B, Brennand KJ, Yagi T, Shen L, Akbarian S.

The methyltransferase SETDB1 regulates a large neuron-specific topological chromatin domain.

Nature Genetics. 2017 Aug;49(8):1239-1250. doi: 10.1038/ng.3906. Epub 2017 Jul 3. PMID:28671686

2016

von Schimmelmann M, Feinberg PA, Sullivan JM, Ku SM, Badimon A, Duff MK, Wang Z, Lachmann A, Dewell S, Ma’ayan A, Han MH, Tarakhovsky A, Schaefer A. Polycomb repressive complex 2 (PRC2) silences genes responsible for neurodegeneration. Nat Neurosci. 2016 Oct;19(10):1321-30. doi: 10.1038/nn.4360.PMID:275262


Hansen T, Venø M, Jensen T, Schaefer A, Damgaard K, and Kjems J. Argonaute-associated short introns are a novel class of gene regulators. Nature Communication. 2016 May 13;7:11538. doi: 10.1038/ncomms11538. PMID: 27173734

2015

Sullivan J, Badimon A, Schaefer U, Ayata P, Gray J, Chung C, von Schimmelmann M, Zhang F, Garton N, Smithers N, Lewis H, Tarakhovsky A, Prinjha R, Schaefer A. Autism-like syndrome is induced by pharmacological suppression of BET proteins in young mice. J Exp Med. 2015 Oct 19;212(11):1771-81. doi: 10.1084/jem.20151271. Epub 2015 Sep 21.

2014

Gao Z, Lee P, Stafford J.M, von Schimmelmann M, Schaefer A, Reinberg D. AUTS2 (Autism Susceptibility Candidate 2) confers transcriptional activation to PRC1 in the CNS. Nature. 2014 Dec 18;516(7531):349-54. doi: 10.1038/nature13921. PMID: 25519132


Lyons DB, Magklara A, Goh T, Sampath SC, Schaefer A, Schotta G, Lomvardas S. Heterochromatin-mediated gene silencing facilitates the diversification of olfactory neurons. Cell Rep. 2014 Nov 6;9(3):884-92. doi: 10.1016/j.celrep.2014.10.001. Epub 2014 Oct 30. PMID: 25437545


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*. *co-corresponding authors. G9a influences neuronal subtype specification in striatum. Nature Neuroscience. 2014 March. doi: 10.1038/ nn.3670. PMID: 24584053

2013

Tan CL, Plotkin JL, Venø MT, von Schimmelmann M, Feinberg P, Mann S, Handler A, Kjems J, Surmeier DJ, O’Carroll D, Greengard P, Schaefer A. MicroRNA-128 governs neuronal excitability and motor behavior in mice. Science. 2013 December; 342 (6163):1254-8. PMID: 24311694

2012

O’Carroll, D. and Schaefer A. General principals of miRNA biogenesis and regulation in the brain. Neuropsychopharmacology Review, 2012 Jun 6. doi: 10.1038/npp.2012.87. PMID: 2431169

2011

Schaefer A, Tarakhovsky A., and Greengard P. Epigenetic mechanisms of mental retardation. Prog Drug Res. 2011; 67:125-46. Review. Epigenetics and Disease, Springer, Basel. PMID: 21141728

Meet the Team

Current

Sarah Veugelen

Sarah Veugelen

Postdoctoral Fellow

sarah.veugelen@mssm.edu

Pinar Ayata

Pinar Ayata

Postdoctoral Fellow

pinar.ayata@mssm.edu

Received NARSAD Young Investigator Award in July/August 2016.

Andrew Chan

Andrew Chan

PhD Student

andrew.chan@icahn.mssm.edu

Josefa Sullivan

Josefa Sullivan

PhD student

josefa.sullivan@mssm.edu

Awarded the NIMH T32 Training Grant for 2014-2015.
NIMH F31
Seaver Graduate Fellow

Ana Badimon

Ana Badimon

PhD student

ana.badimon@mssm.edu

Awared NIA T32 Training grant fellowship 2016.

Mary Duff

Mary Duff

Alumini

Sahil Agrawal

Sahil Agrawal

MD PhD Student

sahil.agrawal@icahn.mssm.edu

Hayley Strasburger

Hayley Strasburger

PhD Student

hayley.strasburger@icahn.mssm.edu

Alumni

Melanie Von Schimmelmann, PhD

Melanie Von Schimmelmann, PhD

Alumini

melanie.vonschimmelmann@mssm.edu

NARSAD Young Investigator Award.

Fan Zhang

Fan Zhang

Alumini

an.zhang@mssm.edu

Miriam Akeju

Miriam Akeju

Alumni

miriam.akeju@mssm.edu

Silas Mann

Silas Mann

Alumni

Naomi Goodman

Naomi Goodman

Alumini

naomi.goodman@mssm.edu

Philip Feinberg

Philip Feinberg

Alumni

philip.feinberg@mssm.edu

Naama Volk

Naama Volk

Alumini

Brianna Ramirez

Brianna Ramirez

Alumini

Brian Safaie

Brian Safaie

Alumini

Brian.Safaie@icahn.mssm.edu

Funding & Awards

Anne Schaefer has been named a 2014 Kavli Frontiers of Science Fellow by the National Academy of Sciences (NAS). The Kavli program honors young scientists who are considered leaders in their fields and have made significant contributions to science. Jointly sponsored by the US National Academy of Sciences and The Kavli Foundation, the Kavli Frontiers of Science bring together some of the very best young scientists (under age 45) to discuss exciting advances and opportunities in their fields in a format that encourages informal collective, as well as one-on-one discussions among participants. Dr. Schaefer was invited to the Japanese-American Frontiers of Science ( JAFoS) Symposium that took place in Tokio in December 2014.

Awards
1999-2003 Scholarship of the German National Merit Foundation
2001-2003 USA-Scholarship of the German National Merit Foundation
2003 Keystone Scholar Travel Award
2004 Summa cum laude, Charité University Berlin
2005 Hans-Hench Award 2005, German Society for Immunology, Germany
2006-2008 German Research Foundation DFG, Research Fellowship, Germany
2011 2010 NARSAD Young Investigator Award, USA
2012 named “Chrissy Rossi Investigator”
2012 Seaver Autism Center Research Award, USA
2012 NIH Director’s New Innovator Award, USA
2014 Technology Development Fund Award, Mount Sinai Innovation, USA
2014 Cure Challenge Award, USA
2014 Kavli Frontiers in Science Fellow, The National Academy of Science, USA
2015 Harold and Golden Lamport Research Award, Mount Sinai, USA
Funding
On Going
09/18/2017-09/17/2019 R21 MH115353-01 (Schafer and Schaefer, PIs)

NIMH
“Exploring novel activity-dependent mechanisms regulating microglia-synapse interactions”
This award aims to elucidate novel proteins involved in neuron activity-mediated microglia-synapse interactions.

12/01/2014-04/01/2019 GSK COL1000039850 (Schaefer, PI)

GSK Research Collaboration Agreement
“Role of BRD proteins in microglia activation”
The aim of the proposed project is to test the ability of the brain permeable I-BET to suppress microglia activation and microglia mediated neurodegeneration.

10/01/2017-09/30/2019 Pfizer COL (Schaefer, PI)

Pfizer Inc., U.S. Pharmaceuticals Group
miR-128 Based Treatment of Fatal Epilepsy in Dravet-like Syndromes
Major goal is to evaluate the therapeutic potential of miR-128 in the treatment of Dravet syndrome

03/01/2017-08/28/2022 M.D. Anderson (Goate, PI,)

Understanding the mechanism of MS4A-dependent AD risk
The goal of this research is to identify candidate the causal gene(s) in the MS4A cluster (an AD-associated locus) and to investigate their role in AD pathogenesis for the development of therapeutic agents.

08/01/2016—07/31/2021 RF1 AG054011-01 (Goate, PI, Schaefer, Co-PI)

NIA
“Understanding the mechanism of SPl1 dependent Alzheimer disease risk”
This award addresses the mechanism of the Alzheimer disease risk gene SPI1 in control of microglia activation in vivo.

09/01/2015—08/31/2019 R01 NS091574-01A1 (Schaefer, PI)
NINDS
“Control of neuron activity and animal behavior by non-coding RNAs”
This award addresses the mechanism and potential therapeutic effects of miR-128 control of epilepsy in mice.
12/01/2014—11/30/2016 GSK COL1000039850 (Schaefer)
GSK Research Collaboration Agreement
“Role of BRD proteins in microglia activation”
The aim of the proposed project is to test the ability of the brain permeable I-BET to suppress microglia activation and microglia mediated neurodegeneration.
09/31/2012—09/30/2017 1 DP2 MH100012-01 (Schaefer)
2012 NIH Director’s New Innovator Award
“Cognate microglia-neuron interaction and its role in inflammation”
This award addresses the molecular basis for cognate neuron-microglia interaction and its role in controlling neuronal function in health and disease.
09/01/2014—08/31/2017 CURE
“Non-coding RNA mediated control of inhibitory and excitatory neuron excitability.”
This award addresses the role of miR-128 in modulating excitatory and inhibitory neuron excitability and associated behavior in mouse models of Dravet syndrome in vivo.
Completed
03/01/2014—02/28/2015 5P30DA035756-02 (Heintz), P30 Pilot Grant (Schaefer)
NIDA, Molecular Definition of Brain Circuits Controlling Addiction
“Analysis of cocaine induced transcriptional memory at a single cell level”
01/01/2012—12/31/2014 Seaver Autism Center Research Award (Schaefer)
Seaver Foundation
“Epigenetic basis of Autism”
01/01/2014—12/31/2014 Technology Development Award 2014 (Schaefer)
Mount Sinai Innovation
“Novel miRNA-based treatment of severe Epilepsy.”
07/15/2011—07/14/2013 2010 Young Investigator Award, Grant# 18194
(Schaefer)
NARSAD, The Brain and Behavioral Research Fund
“Epigenetic regulation of depression”
01/09/2008—08/31/2010 1RO3DA025962 (Schaefer)
NIDA
“The role of miRNAs in Cocaine Addiction”
12/22/2008—12/21/2011 W81XWH-09-1-0095 (Schaefer)
U. S. Army Medical Research and Materiel Command (USAMRMC)
“Role of miRNAs inParkinson’s Disease”

Featured

Featured Publication

Polycomb repressive complex 2 (PRC2) silences genes responsible for neurodegeneration. Schimmelmann M, Feinberg PA, Sullivan JM, Ku SM, Badimon A, Duff MK, Wang Z, Lachmann A, Dewell S, Ma’ayan A, Han MH, Tarakhovsky A, Schaefer A. Nat Neurosci. 2016 Oct;19(10):1321-30. doi: 10.1038/nn.4360.PMID:275262.

Normal brain function depends on the interaction between highly specialized neurons that operate within anatomically and functionally distinct brain regions.

Life and death rest on a bivalent chromatin state

News and views by William Yang. Yang XW. Life and death rest on a bivalent chromatin state. Nature Neuroscience 19,1271–1273(2016) doi:10.1038/nn.4396

Defect in Process That Controls Gene Expression May Contribute to Huntington’s Disease and Other Neurodegenerative Disorders —August 15, 2016.

A protein complex called Polycomb Repressive Complex 2 (PRC2), which plays a critical role in forming specific classes of nerve cells in the brain during development, also plays an important role in the adult brain where it may contribute to Huntington’s disease and other neurodegenerative disorders

— MountSinai.org

Suppression of Epigenetic Brain Proteins Induces Autism-Like Syndrome

MountSinai.org — October 8, 2015. Read more
NeuroScientistNews — October 15, 2015. Read more
ScienceDaily — October 15, 2015. Read more

Patents

Compositions and Methods for Modulating Neuronal Excitability and Motor Behavior

A. Schaefer, P. Greengard. US provisional patent application No. 61/898,952 and No. 61/896,463. Filed October 28th 2013. Full PCT application executed November 2014, International application number PCT/US2014/062664

Methods And Compositions For Translational Profiling And Molecular Phenotyping

N. Heintz, P. Greengard, M. Heiman, A. Schaefer, J. Doyle, J. Dougherty. Publication No. US 2011/0071049 A1 published 2011

In the Press

How dying neurons control eating behaviors of the brain microglia
Aberrant clearance activity of microglia in particular brain regions leads to changes associated with neurodegenerative diseases — July 23, 2018. Read more

The Mount Sinai Hospital / Mount Sinai School of Medicine
Study provides insight into how dying neurons control eating behaviors of the brain microglia — July 23, 2018. Read more

BET protein family plays key role in regulation of normal neuronal development and function.
News Medical Life Sciences and Medicine — October 19, 2015. Read more

Mount Sinai Innovation Partners
Single microRNA powers motor activity: Findings have implications for treating sever treatment-refractory epilepsy, says Mount Sinai researcher. Read more

Science Daily
Dec. 5, 2013 — New research from the Icahn School of Medicine at Mount Sinai shows that microRNA-128 is one of the strongest regulators of nerve cell excitability and motor activity, and that it does so by adjusting an entire neuronal signaling pathway. Read more

Yahoo! Groups
Sagital brain section of a miR-128 deficient mouse. Immunostaining shows normal striatal neurons and their projections to the substantia nigra (green fluorescent protein shown in green) in wild-type and miR-128 deficient mice. Read more

Genomeweb
New Research Links miR-128 with Motor Hyperactivity, Epilepsy Read more

Visembryo
Research on mice shows that microRNA-128 has a direct effect on the musculoskeletal system. When it is increased, neuron activity is lowered – reducing uncontrolled movements in connection with epilepsy or Parkinson’s. When decreased, microRNA-128 boosts neuron activity. Read more

Anne Schaefer, MD, PhD, of Mount Sinai School of Medicine Receives Prestigious National Institutes of Health Director’s New Innovator Award
Anne Schaefer, MD, PhD, Assistant Professor of Neuroscience, and Psychiatry, at Mount Sinai School of Medicine, has been recognized with the highly celebrated 2012 Director’s New Innovator Award from the National Institutes of Health (NIH). Dr. Schaefer is among 51 recipients of the award nationwide. Read more

Job Openings

The Laboratory of Brain Epigenetics has immediate openings for Postdoctoral Scientists. We seek highly motivated individuals with a considerable background in Neuroscience, Molecular Biology, Cell Biology, Mouse Genetics and/or Biochemistry. Individuals with an expertise in mRNA/miRNA or chromatin analysis are particularly encouraged to apply. Applicants should possess a Ph.D. and/or M.D. degree.

Please send a cover letter, curriculum vitae, and the names, phone numbers and e-mail addresses of three people who could provide letters of reference by email to anne.schaefer@mssm.edu.