This is the competitive renewal for a grant that has led to several key discoveries in the field of oligodendrocyte cell identity. Based on our previous record of productivity, solid preliminary data and resources and the collaboration with leaders in the field of epigenetics, chromatin and system biology, we propose to continue to elucidate mechanisms of oligodendrocyte differentiation and myelin formation. The proposed experimental plan will impact not only the field of neurobiology, but also address important biological questions with implications for a broad range of disciplines and contribute to the development of novel therapeutic strategies.

Public Health Relevance

Epigenetic mechanisms serve as an interface between the environment and gene expression and they are responsible for the long-lasting changes in nuclear chromatin that define cell identity. We study these mechanisms in oligodendrocyte lineage cells. The goal is to define their potential role for repair of neonatal and adult neuropathologies as well as psychiatric disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37NS042925-12
Application #
8696888
Study Section
Cellular and Molecular Biology of Glia Study Section (CMBG)
Program Officer
Morris, Jill A
Project Start
2001-12-01
Project End
2016-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
12
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Neurosciences
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029
Pathak, Amrita; Stanley, Emily M; Hickman, F Edward et al. (2018) Retrograde Degenerative Signaling Mediated by the p75 Neurotrophin Receptor Requires p150Glued Deacetylation by Axonal HDAC1. Dev Cell 46:376-387.e7
McKenzie, Andrew T; Wang, Minghui; Hauberg, Mads E et al. (2018) Brain Cell Type Specific Gene Expression and Co-expression Network Architectures. Sci Rep 8:8868
Schlüter, Agatha; Sandoval, Juan; Fourcade, Stéphane et al. (2018) Epigenomic signature of adrenoleukodystrophy predicts compromised oligodendrocyte differentiation. Brain Pathol 28:902-919
Casaccia, Patrizia; Corfas, Gabriel (2018) Introduction to the special issue on myelin plasticity in the central nervous system. Dev Neurobiol 78:65-67
Liu, Jia; Dietz, Karen; Hodes, Georgia E et al. (2018) Widespread transcriptional alternations in oligodendrocytes in the adult mouse brain following chronic stress. Dev Neurobiol 78:152-162
Motl, Robert W; Mowry, Ellen M; Ehde, Dawn M et al. (2018) Wellness and multiple sclerosis: The National MS Society establishes a Wellness Research Working Group and research priorities. Mult Scler 24:262-267
Ntranos, Achilles; Casaccia, Patrizia (2018) The Microbiome-Gut-Behavior Axis: Crosstalk Between the Gut Microbiome and Oligodendrocytes Modulates Behavioral Responses. Neurotherapeutics 15:31-35
Scaglione, Antonella; Patzig, Julia; Liang, Jialiang et al. (2018) PRMT5-mediated regulation of developmental myelination. Nat Commun 9:2840
Cekanaviciute, Egle; Yoo, Bryan B; Runia, Tessel F et al. (2017) Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc Natl Acad Sci U S A 114:10713-10718
McKenzie, Andrew T; Moyon, Sarah; Wang, Minghui et al. (2017) Multiscale network modeling of oligodendrocytes reveals molecular components of myelin dysregulation in Alzheimer's disease. Mol Neurodegener 12:82

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