Marcelo A WoodAssistant Professor, Neurobiology and Behavior |
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Research Interests |
Long-term Memory Storage, Transcription, Histone Acetyltransferases, Histone Deacetylases, Gene Expression | |
| URL | Lab Homepage | |
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Research Abstract |
Long-term memory storage is an essential process to human life. Without long-term memory, we would not be able to remember our pasts, interpret our present, or predict our future. We would have little personal identity and functioning in a world that continues to grow in complexity would be impossible. Our research goal in the Wood lab is to understand the molecular mechanisms underlying long-term memory storage. Transcriptional activation is thought to be a key process in long-lasting forms of memory and synaptic plasticity. This activation is directed by transcription factors and their coactivators, which regulate gene activation via chromatin remodeling activity or histone covalent modification activity as well as mediating interactions with basal transcription machinery components. One type of histone modification associated with transcriptional activation is acetylation, which is regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) that add or remove acetyl groups from histones, respectively. Rubinstein-Taybi Syndrome (RTS), a human developmental disorder characterized by retarded growth and reduced mental function, is caused by deletions, translocations, or point mutations in the CREB-binding protein (CBP) gene. CBP is a transcriptional coactivator that mediates gene expression via direct interactions with the basal transcription machinery as well as its intrinsic HAT activity. Using genetically modified mice, we demonstrated that CBP is critical for hippocampus-dependent long-term memory and hippocampal synaptic plasticity (Wood et al. 2005). To explore the relationship between histone acetylation and memory storage we tested the hypothesis that increasing histone acetylation would enhance memory storage. We found that the histone deacetylase inhibitor trichostatin A increases histone acetylation and enhances memory consolidation for a hippocampus-dependent task and enhances hippocampal synaptic plasticity. Together, our studies using genetically modified mice and neuropharmacology demonstrate the pivotal role of CBP and histone acetylation in memory and synaptic plasticity and suggest that their exists a layer of transcriptional regulation at the epigenetic level for the expression of genes for long-term memory processes. Further, our studies indicate that histone deacetylase inhibitors are a potential treatment for the cognitive deficits that accompany many psychiatric and neurological disorders such as RTS and Huntington’s Disease. Current projects in the lab center around examining the role of epigenetic regulation of transcription for long-term memory processes using a combined molecular, genetic, and behavioral approach. |
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| Publications |
McMahon SB, Wood MA, and Cole MD (2000) The c-Myc cofactor TRRAP recruits the histone acetylase hGCN5. Mol Cell Biol v20:556-562. Wood MA, McMahon SB, and Cole MD (2000) An ATPase/helicase complex is an essential cofactor for oncogenic transformation by c-Myc. Molecular Cell. v5:321-330. Park J, Wood MA, and Cole MD (2002) BAF53 forms distinct nuclear complexes and functions as a critical c-Myc-interacting nuclear cofactor for oncogenic transformation. Mol Cell Biol v22:1307-16. Dugan KA, Wood MA, and Cole MD (2002) TIP49, but not TRRAP, modulates c-Myc and E2F1 dependent apoptosis. Oncogene. v21:5835-43. Wood MA, Kaplan MP, Park A, Blanchard EJ, Lombardi TL, and Abel T (2005) Transgenic mice expressing a truncated form of CREB-binding protein (CBP) exhibit deficits in hippocampal synaptic plasticity and memory storage. Learning & Memory. v12:111-119. Wood MA, Kaplan MP, and Abel T (2005) Ubiquitin C-terminal esterase 3 (Uch-L3) is involved in working memory. Hippocampus. v15:610-621. Zhang B, Veasey S, Wood MA, Leng LZ, Kaminski C, Leight S, Abel T, Lee VMY, and Trojanowski JQ (2005) Impaired rapid eye movement sleep in the Tg 2576 APP murine model of Alzheimer’s Disease with injury to pedunculopontine cholinergic neurons. Am J of Pathology. v167:1361-1369. Keeley MB, Wood MA, Isiegas C, Stein J, Hellman K, Hannenhalli S, and Abel T (2006) Differential transcriptional response to non-associative and associative components of classical fear conditioning in the amygdala and hippocampus. Learning & Memory. v13:135-142. Wood MA, Hawk JD, and Abel T (2006) Combinatorial chromatin modifications and memory storage: A code for memory? Learning & Memory. v13:241-244. Oliveira AMM, Abel T, Brindle PK, and Wood MA (2006) Differential role for CBP and p300 CREB-binding domain in motor skill learning. Behav Neurosci. v120:724-729. Wood MA, Attner MA, Oliveira AMM, Brindle PK, and Abel T (2006) A transcription factor-binding domain of the coactivator CBP is essential for long-term memory and expression of specific target genes. Learning & Memory. v13:609-617. Oliveira AM, Wood MA, McDonough CB, and Abel T (2007) Transgenic mice expressing an inhibitory truncated form of p300 exhibit long-term memory deficits. Learning & Memory. v14:564-572. Vecsey CG, Hawk JD, Lattal KM, Stein JM, Fabian SA, Attner MA, Cabrera SM, McDonough CB, Brindle PK, Abel T, and Wood MA (2007) Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation. J Neurosci. v27:6128-6140 Lattal KM, Barrett RM, and Wood MA (2007) Systemic or intrahippocampal delivery of histone deacetylase inhibitors facilitates fear extinction. Behav Neurosci. v121:1125-1131. |
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| Barrett RM and Wood MA (2008) Beyond transcription factors: The role of chromatin modifying enzymes in regulating transcription required for memory. Learning & Memory v15:460-467. | ||
| Jiang Y, Langley B, Lubin F, Renthal W, Wood MA, Yasui D, Kumar A, Nestler E, Akbarian S, and Beckel-Mitchener A (2008) Epigenetics in the Nervous System. J Neurosci v28:11753-9. | ||
| Pham J, Cabrera SM, Sanchis-Segura C, and Wood MA (2009) Automated scoring of fear related behavior using EthoVision software. J Neurosci Methods v178:323-326. | ||
| Stefanko DP, Barrett RM, Ly AR, Reolon GK, and Wood MA (2009) Modulation of long-term memory for object recognition via HDAC inhibition. Proc Natl Acad Sci v106:9447-9452. | ||
| Grants | Whitehall Foundation | |
| NIH-NIMH R01MH081004 | ||
| NIH-NIDA R01DA025922 | ||
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Professional Societies |
Society for Neuroscience International Behavioral Neuroscience Society Molecular and Cellular Cognition Society Nu Rho Psi National Honor Society in Neuroscience |
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| Graduate Programs |
Neurobiology and Behavior |
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| Research Centers | Center for the Neurobiology of Learning and Memory | |
| Institute for Memory Impairments and Neurological Disorders | ||
| Link to this profile | http://www.faculty.uci.edu/profile.cfm?faculty_id=5317 | |
| Last updated | 07/10/2009 | |