Stephen J. Haggarty, PhD

  • Lab Phone: 617-643-3201

Research Investigator Profile

Affiliations

Stephen J. Haggarty, PhD

Collaborators

  • Thomas Nieland, PhD,
    Broad Institute - The Stanley Center for Psychiatric Research

Stephen J. Haggarty, PhD

  • Assistant Professor of Neurology,
    Harvard Medical School
  • Assistant in Neuroscience,
    Massachusetts General Hospital
  • Director, Chemical Neurobiology,
    Stanley Center for Psychiatric Research

Research Description

Dr. Haggarty’s long-term goal is to understand how changes in brain chemistry influence the neural circuits underlying mood and memory and the relevance of these changes to the etiology and treatment of brain disease. His research program involves combining synthetic chemistry, neuroscience, and human genetics. Using this chemical genomic approach, members of his group invent new methods for finding small-molecule probes that target key components of the neurocircuitry, and then use these probes to selectively perturb neuronal network function at the molecular, cellular and circuit level. Dr. Haggarty hopes his work will lead to novel therapeutic approaches to treating neuropsychiatric and neurodegenerative disorders. These studies entail three types of experiments:

  1. The development of novel cellular and biochemical assays for screening small molecules, RNAi, and cDNA libraries in order to discover agents for targeting disease-relevant mechanisms and pathways identified by human genetics.
  2. The identification of targets and functional characterization of new molecular probes using proteomic methods and biochemical assays in brain tissues and live cell models, including primary neurons neural stem cell models.
  3. Testing compounds employing a new mechanism of action in animal behavioral models relevant to mood and memory disorders.
Research interests

Neuropharamacology, neuroplasticity, neurotrophic factors, behavior, dopamine, chromatin remodeling, lithium, GSK-3 drug discovery, therapeutics, stem cells
Research techniques Chemistry, high-throughput screens, proteomics, gene expression profiling, molecular biology, chemical biology, imaging
Diseases studied Mood disorders, bipolar disorder, depression, schizophrenia, fragile X syndrome
Selected publications
  1. Kim, D., Frank, C.L., Dobbin, M.M., Tsunemoto, R.K., Tu, W., Peng, P.L., Guan, J.S., Lee, B.H., Moy, L.Y., Giusti, P., Broodie, N., Mazitschek, R., Delalle I., Haggarty, S.J., Neve, R.L., Lu, Y. & Tsai, L.H. (2008). Deregulation of HDAC1 and chromatin state by p25/Cdk5 in neurotoxicity. Neuron, 60:803-817.
  2. Mao, Y., Ge, X., Frank, C.L., Madison, J., Koehler, A.N., Doud, M.K., Tassa, C., Berry, E.M., Petryshen, T.L., Soda, T., Biechele, T., Moon, R.T., Haggarty, S.J. & Tsai, L.H. (2009). DISC1 regulates neural progenitor proliferation via modulation of GSK3/-catenin signaling. Cell, 136:1017-1031.
  3. Guan, J.S., Haggarty, S.J., Giacometti, E., Dannenberg, J.H., Joseph N., Gao, J., Nieland, T.J.F., Zhou, Y., Wang, X., Mazitschek, R., Bradner, J.E., DePinho, R.A., Jaenisch, R. & Tsai, L.H. (2009). HDAC2 negatively regulates memory formation and synaptic plasticity. Nature, 459:55-60.
  4. James, R.G., Biechele, T.L., Conrad, W.H., Camp, N.D., Major, M. M. Sommer, K., Yi X.H., Fass, D.M., Roberts, B., Major, M.B., Cleary, M.A., Arthur, W.T., MacCoss, M., Rawlings, D.J., Haggarty, S.J. & Moon, R.T. (2009). Bruton's tyrosine kinase revealed as a negative regulator of Wnt/-catenin signaling. Science Signaling 2:ra25.
  5. Covington, H.E., Maze, I.S., LaPlant, Q.C., Vialou, V.F., Yoshinori, O.N., Berton, O., Fass, D.M., Renthal, W., Rush, A.J., Wu, E.T., Ghose, S., Krishnan, V., Russo, S.J., Tamminga, C., Haggarty, S.J. & Nestler. E.J. (2009). Antidepressant actions of HDAC inhibitors. Journal of Neuroscience, 29:11451-11460.
  6. Kilgore, M., Miller, C.A., Fass, D.M., Hennig, K.M., Haggarty, S.J., Sweatt, J.D. & Rumbaugh, G. (2009). Inhibitors of class I histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer's disease.  Neuropsychopharmacology, 35:870-880.
  7. Bradner, J.E., West, N., Grachan, M.L., Greenberg, E.F., Haggarty, S.J., Warnow, T. & Mazitsheck, R. (2010). Chemical phylogenetics of histone deacetylases. Nature Chemical Biology, 6:238-243.
  8. Maze, I.S., Covington, H.E., Laplant, Q.C., Renthal, W., Fass D.M., Haggarty, S.J., Tarakhovsky A. & Nestler, E.J. (2010). Histone methylation in the nucleus accumbens controls behavioral responses to cocaine. Science, 327:213-216.
  9. Kuai, L., Wang, X., Madison, J.M., Schreiber, S.L., Scolnick, E.M, & Haggarty, S.J. (2010). Chemical genetics identifies small-molecule modulators of neuritogenesis involving neuregulin-1/ErbB4 signaling. ACS Chemical Neuroscience, 1:325-342.
NCBI PubMed link NCBI PubMed Publications
E-mail address haggarty@chgr.mgh.harvard.edu
Lab mailing address Center for Human Genetic Research
Simches Research Center, CPZN-5242
185 Cambridge Street
Boston, MA 02114
Lab websites

http://www2.massgeneral.org/chgr/faculty_haggarty.htm
Haggarty Lab, Chemical Genomics Laboratory,
Center for Human Genetic Research

 

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