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.
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.
|Magri, Laura; Swiss, Victoria A; Jablonska, Beata et al. (2014) E2F1 coregulates cell cycle genes and chromatin components during the transition of oligodendrocyte progenitors from proliferation to differentiation. J Neurosci 34:1481-93|
|Magri, L; Gacias, M; Wu, M et al. (2014) c-Myc-dependent transcriptional regulation of cell cycle and nucleosomal histones during oligodendrocyte differentiation. Neuroscience 276:72-86|
|Gacias, Mar; Gerona-Navarro, Guillermo; Plotnikov, Alexander N et al. (2014) Selective chemical modulation of gene transcription favors oligodendrocyte lineage progression. Chem Biol 21:841-54|
|Narayanan, Manikandan; Huynh, Jimmy L; Wang, Kai et al. (2014) Common dysregulation network in the human prefrontal cortex underlies two neurodegenerative diseases. Mol Syst Biol 10:743|
|Dutta, Dipankar J; Zameer, Andleeb; Mariani, John N et al. (2014) Combinatorial actions of Tgf? and Activin ligands promote oligodendrocyte development and CNS myelination. Development 141:2414-28|
|Huynh, Jimmy L; Garg, Paras; Thin, Tin Htwe et al. (2014) Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains. Nat Neurosci 17:121-30|
|Bharadwaj, Rahul; Jiang, Yan; Mao, Wenjie et al. (2013) Conserved chromosome 2q31 conformations are associated with transcriptional regulation of GAD1 GABA synthesis enzyme and altered in prefrontal cortex of subjects with schizophrenia. J Neurosci 33:11839-51|
|Huynh, Jimmy L; Casaccia, Patrizia (2013) Epigenetic mechanisms in multiple sclerosis: implications for pathogenesis and treatment. Lancet Neurol 12:195-206|
|Gacias, Mar; Casaccia, Patrizia (2013) Promoting return of function in multiple sclerosis: An integrated approach. Mult Scler Relat Disord 2:|