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Lab Phone: 617-726-0332
Office Phone: 617-724-1487
MassGeneral Institute for Neurodegenerative Disease (MIND)
The NeuroEpigenetics laboratory at MGH/MIND, under the direction of Dr. Ghazaleh Sadri-Vakili, PhD, investigates the molecular mechanisms that underlie alterations in gene expression in disorders of the nervous system using the most current molecular biology tools. Currently, our efforts are focused on Huntington’s disease as well as addiction. Thus far, we have identified a number of epigenetic alterations that lead to changes in gene expression in animal and cell models of Huntington’s disease and drug abuse.
The Huntington’s disease projects are focused on the study of histone modifications, in particular histone acetylation. Our previous findings have shown that alteration in histone acetylation is one mechanism that underlies transcriptional dysregulation in Huntington’s disease. Targeting histone modifying enzymes such as histone deacetylases is a novel approach for the treatment of several neurodegenerative disorders including Huntington’s disease. Currently, as a collaborative effort we are focused on identifying specific and novel histone deacetylase inhibitors for the treatment of Huntington’s disease. We apply the most current techniques, such as chromatin immunoprecipitation, real-time PCR, and genome-wide location analysis, and use both cell as well as animal models of Huntington’s disease for our studies.
The NeuroEpigenetics lab is also interested in investigating the molecular mechanisms that underlie drug abuse as part of several collaborations with colleagues from MGH, University of Pennsylvania, and Mclean Hospital. It is now clear that repeated intake of drugs of abuse alters gene expression in limbic nuclei that underlies the neuronal and behavioral plasticity that characterizes addiction. Our research is aimed at identifying the epigenetic marks involved in the regulation of cocaine-induced alterations in gene expression in limbic nuclei. More specifically work from our laboratory focuses on determining how cocaine-induced chromatin remodeling leads to alterations in brain-derived neurotrophic factor (BDNF) expression within the medial prefrontal cortex following exposure to cocaine. Our most recent efforts are focused on determining whether these specific epigenetic marks are heritable and persist beyond the F1 generation in rodents exposed to cocaine prenatally or via self-administration.
Ghazaleh Sadri-Vakili, MS, PhD
Huntington's disease study
Histone deacetylase inhibitors (HDACi) inhibit the activity of histone deacetylases, keeping chromatin in an “active” euchromatin state, thereby promoting gene expression.
Cocaine addiction study
Cocaine self-administration followed by 7 days of forced abstinence, increases BDNF expression in the prefrontal cortex by decreasing MeCP2 binding, and increasing phospho-CREB and histone acetylation at BDNF promoter IV.
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MassGeneral Institute for Neurodegenerative Disease
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Anne B. Young, MD, PhDDirector, Massgeneral Institute for Neurodegenerative Disease Professor of Neurology, Harvard Medical School
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