Our 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.
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]
Featured as news and views at Nature neuroscience: https://www.nature.com/articles/s41593-018-0196-z
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
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
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.
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
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
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
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
Received NARSAD Young Investigator Award in July/August 2016.
Melanie Von Schimmelmann, PhD
NARSAD Young Investigator Award.
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.
|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|
|09/18/2017-09/17/2019||R21 MH115353-01 (Schafer and Schaefer, PIs)
|12/01/2014-04/01/2019||GSK COL1000039850 (Schaefer, PI)
GSK Research Collaboration Agreement
|10/01/2017-09/30/2019||Pfizer COL (Schaefer, PI)
Pfizer Inc., U.S. Pharmaceuticals Group
|03/01/2017-08/28/2022||M.D. Anderson (Goate, PI,)
Understanding the mechanism of MS4A-dependent AD risk
|08/01/2016—07/31/2021||RF1 AG054011-01 (Goate, PI, Schaefer, Co-PI)
|09/01/2015—08/31/2019||R01 NS091574-01A1 (Schaefer, PI)
“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.
“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.
|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)
“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
NARSAD, The Brain and Behavioral Research Fund
“Epigenetic regulation of depression”
“The role of miRNAs in Cocaine Addiction”
U. S. Army Medical Research and Materiel Command (USAMRMC)
“Role of miRNAs inParkinson’s Disease”
Normal brain function depends on the interaction between highly specialized neurons that operate within anatomically and functionally distinct brain regions.
Defect in Process That Controls Gene Expression May Contribute to Huntington’s Disease and Other Neurodegenerative Disorders —August 15, 2016.
In The Press
Huntington’s Disease News — August 19, 2016
Defect in process that controls gene expression may contribute to Huntington’s disease
Science Daily — August 15, 2016
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
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
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
New Research Links miR-128 with Motor Hyperactivity, Epilepsy Read more
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
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 email@example.com.