Ghazaleh Sadri-Vakili, MS, PhD - The NeuroEpigenetics Laboratory is delineating molecular mechanisms underlying alterations in transcription of target genes in Huntington's disease, addiction, and Autism Spectrum Disorders.

  • Lab Phone: 617-726-0332
  • Office Phone: 617-724-1487

Research Investigator Profile

Portrait image of Dr. Sadri-Vakili

Ghazaleh Sadri-Vakili, MS, PhD

  • Assistant Professor of Neurology,
    Harvard Medical School
  • Assistant in Neuroscience,
    Massachusetts General Hospital

 

 

Research Description

The NeuroEpigenetics laboratory at Mass General's 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. Read more at the Sadri-Vakili NeuroEpigenetics Lab.

Research interests Epigenetic regulation of gene expression leading to problems with neurodevelopment, neurodegeneration, and addiction.
Research techniques Molecular biology and biochemistry: chromatin immunoprecipitation (ChIP); genome-wide location analysis; real-time PCR; DNA, RNA & protein analysis
Diseases studied Huntington's disease, addiction, Autism Spectrum Disorders
Selected publications
  1. McCarthy, D., Zhang, X., Darnell, S.B., Sangrey, G.R., Yanagawa, Y., Sadri-Vakili, G., and Bhide, P.G. (2011) Cocaine alters BDNF expression and neuronal migration in the embryonic mouse forebrain. Journal of Neuroscience 31:13400-13411.
  2. Anderson, S.M.*, Famous, K.R.*, Sadri-Vakili, G.*, Kumaresan, V.*, Schmidt, H.D., Bass, C., Terwilliger, Cha, J.-H.J. and Pierce, R.C. (2008) CaMKII: the biochemical bridge linking nucleus accumbens dopamine and glutamate systems in cocaine seeking. Nature Neuroscience 11(3):344-353. * Equal contribution.
  3. Kim, M., Chawla, P., Overland, R.P., Sadri-Vakili, G., Cha, J.-H.J.  (2008) Mutant Huntingtin-mediated histone monoubiquitylation induces transcriptional dysregulation in Huntington’s disease. J Neuroscience 28(15):3947-57.
  4. Sadri-Vakili, G., Bouzou, B., Benn, C.L., Kim, M., Chawla, P., Overland, R.P., Glajch, K.E., Xia, E., Qui, Z., Hersch, S.M., Clark, T.W., Yohrling, G.J., Cha, J.-H.J. (2007) Histones Associated with Downregulated Genes are Hypo-acetylated in Huntington’s Disease Models. Human Molecular Genetics 16(11):1293-306.
  5. Sadri-Vakili, G. & Cha, J.-H.J. (2006) Mechanisms of disease: histone modifications in Huntington’s disease.  Nature Clinical Practice Neurology 2(6):330-338.
View more selected publications
NCBI PubMed link NCBI PubMed Publications
Collaborators R. Christopher Pierce, University of Pennsylvania; Stephanie Licata, PhD, McLean Hospital;
E-mail address gsadrivakili@partners.org
Lab mailing address

MassGeneral Institute for Neurodegenerative Disease
Building 114, 16th Street, Room 2200
Charlestown, MA 02129

Lab website NeuroEpigenetics Laboratory

1. Sadri-Vakili, G. & Cha, J.-H.J. (2006) Mechanisms of disease: histone modifications in Huntington’s disease.  Nature Clinical Practice Neurology 2(6):330-338.

2. Sadri-Vakili, G.,
Bouzou, B., Benn, C.L., Kim, M., Chawla, P., Overland, R.P., Glajch, K.E., Xia, E., Qui, Z., Hersch, S.M., Clark, T.W., Yohrling, G.J., Cha, J.-H.J. (2007) Histones Associated with Downregulated Genes are Hypo-acetylated in Huntington’s Disease Models.  Human Molecular Genetics 16(11):1293-306.

3.
Kim, M., Chawla, P., Overland, R.P., Sadri-Vakili, G., Cha, J.-H.J.  (2008) Mutant Huntingtin-mediated histone monoubiquitylation induces transcriptional dysregulation in Huntington’s disease. J Neuroscience 28(15):3947-57.

4. Anderson, S.M.*, Famous, K.R.*, Sadri-Vakili, G.*, Kumaresan, V.*, Schmidt, H.D., Bass, C., Terwilliger, Cha, J.-H.J. and Pierce, R.C. (2008) CaMKII: the biochemical bridge linking nucleus accumbens dopamine and glutamate systems in cocaine seeking. Nature Neuroscience 11(3):344-353.
* Equal contribution.

5. Sadri-Vakili, G., Kumaresan, V., Famous, K.R., Chawla, P., Darnell S.B., Muhammad, S.I. Vassoler, F., Xia,E., Overland, R.P., Schmidt, H.D., Bass, C.E., Terwilliger, E.F., Pierce, R.C., and Cha, J.H.J. Epigenetic regulation of BDNF in the rat medial prefrontal cortex alters the reinforcing efficacy of cocaine. Journal of Neuroscience 2010; 30(35):11735-11744.
 
6. McCarthy, D., Zhang, X., Darnell, S.B., Sangrey, G.R., Yanagawa, Y., Sadri-Vakili, G., and Bhide, P.G. (2011) Cocaine alters BDNF expression and neuronal migration in the embryonic mouse forebrain. Journal of Neuroscience 31:13400-13411.