Faculty Member, Institute for Genome Sciences; Faculty Member, Maryland Psychiatric Research Center
801 West Baltimore Street Baltimore, MD 21201
Education and Training
Ph.D. University of Illinois at Urbana-Champaign (Neuroscience, 2010)
A.B. Harvard University (Biology, 2003)
Neuropsychiatric disorders are among the leading causes of disability in the United States and worldwide. I study the genetic causes and biological mechanisms of neuropsychiatric disorders, using human genetics, systems biology, and stem cells. Systems genetics combines statistical genetics with network biology to discover mechanisms for complex traits, powered by exponential rises in genomic data. The long-term goals of these studies are to gain insight into the regulation of brain function and to enable the development of more precise diagnostics and therapies for psychiatric disease. I joined the faculty of the University of Maryland School of Medicine in September, 2016, following postdoctoral fellowships at the Institute for Systems Biology in Seattle, Washington, where I worked with Leroy Hood and Nathan Price, and at the University of California, Berkeley. where I worked with Kristin Scott. I completed my doctoral work in the laboratory of Gene Robinson at the University of Illinois in Urbana-Champaign, where I studied molecular mechanisms of honey bee social behavior.
Bipolar disorder; schizophrenia; genetics; genomics; systems biology; stem cells; neuron; brain; behavior
- Ament S.A., Szelinger S., Glusman G., Ashworth J., Hou L., Akula N., Shekhtman T., Badner J.A., Brunkow M.E., Mauldin D.E., Stittrich A.B., Rouleau K., Detera-Wadleigh S., Nurnberger J.I., Edenberg H.J., Gershon E.S., Schork N.J., The Bipolar Genome Study, Price N.D., Gelinas R., Hood L., Craig D.W., McMahon F.J., Kelsoe J.R., and Roach J.C. (2015) Rare variants in neuronal excitability genes influence risk for bipolar disorder. Proc Natl Acad Sci USA. 112(11):3576-3581.
- Ko Y.*, Ament S.A.*, Caballero J., Earls J.C., Hood L., Price N.D. (2013) Cell-type specific genes show striking and distinct patterns of spatial expression in the mouse brain. Proc Natl Acad Sci USA. 110(8):3095-3100.
- Chandrasekaran S., Ament S.A., Eddy J.A., Rodriguez-Zas S.R., Schatz B.R., Price N.D., and Robinson G.E. (2011) Behavior-specific changes in transcriptional modules lead to distinct and predictable neurogenomic states. Proc Natl Acad Sci USA. 108:18020-18025.
- Ament S.A.*, Pearl J.R.*, Bragg R.M., Skene P., Coffey S.R., Plaisier C.L., Wheeler V.C., MacDonald M.E., Baliga N.S., Rosinski J., Hood L.E., Carroll J.B., and Price N.D. Genome-scale transcriptional regulatory network models for the mouse and human striatum predict roles for SMAD3 and other transcription factors in Huntington’s disease. bioRxiv. http://biorxiv.org/content/early/2016/11/10/087114
- Ament S.A., Bullis R., Hanlon R.T., and Mensinger A. (1997) Righting response and escape response in Opsanus tau are temperature dependent. Biol Bull193:265-266.
- Hanlon R.T., Ament S.A., and Gabr H. (1999) Behavioral aspects of sperm competition in cuttlefish, Sepia officinalis (Sepioidea: Cephalopoda). Marine Biol 134:719-728.
- Shashar N., Borst D.T., Ament S.A., Saidel W.M., Smolowitz R.M., and Hanlon R.T., (2001) Polarization reflecting iridophores in the arms of the squid Loligo pealeii. Biol Bull 201:267-268.
- Honeybee Genome Sequencing Consortium (2006) Insights into social insects from the genome of the honeybee Apis mellifera. Nature 443:931-49.
- Kunieda T.*, Fujiyuki T.*, Kucharski R.*, Foret S.*, Ament S.A.*, Toth A.L.*, Ohashi K., Takeuchi H., Kamikouchi A., Kage E., Morioka M., Beye M., Kubo T., Robinson G.E., and Maleszka R. (2006) Carbohydrate metabolism genes and pathways in insects: insights from the honey bee genome. Insect Mol Biol 15:563-576.
- Ament S.A., Corona M., Pollock H.S., and Robinson G.E. (2008) Insulin signaling is involved in the regulation of worker division of labor in honey bee colonies. Proc Natl Acad Sci USA, 105:4226-4231.
- Brockmann A. AnnangudiS.P., RichmondT.A., AmentS.A., XieF., SoutheyB.R., Rodriguez-ZasS.R., SweedlerJ.V., and RobinsonG.E. (2009) Quantitative peptidomics reveal brain peptide signatures of behavior. Proc Natl Acad Sci USA. 106:2383-2388.
- Ament S.A., Wang Y., and Robinson G.E. (2010) Nutritional regulation of worker division labor in honey bee colonies: a systems perspective. Wiley Interdiscipl Rev: Systems Biol Med. 2(5):566-576.
- Ament S.A., Velarde R.A., Kolodkin M., Moyse D., and Robinson G.E. (2011) Neuropeptide Y-like signaling and nutritionally-mediated gene expression and behavior in the honey bee. Insect Mol Biol. 20(3):335-345.
- Ament S.A., Chan Q.W., Wheeler M.W., Nixon S.E., Johnson S.P., Rodriguez-Zas S.R., Foster L.J., and Robinson G.E. (2011) Mechanisms of stable lipid loss in a social insect. J Exp Biol. 214:3808-3821.
- Ament S.A.*, Wang Y.*, Chen C.-C., Blatti C., Hong F., Negre N., White K.P., Rodriguez-Zas S.L., Mizzen C.A., Sinha S., Zhong S., and Robinson G.E. (2012) The transcription factor ultraspiracle influences honey bee social behavior and behavior-related gene expression. PLoS Genet. 8(3):e1002596.
- Ament S.A.*, Blatti C.*, Alaux C.*, Wheeler M.W., Toth A.L., Le Conte Y., Hunt G.J., Guzmán-Novoa E., DeGrandi-Hoffman G., Uribe-Rubio J.L., Amdam G.V., Page R.E., Rodriguez-Zas S.L, Robinson G.E. and Sinha S. (2012) New meta-analysis tools reveal common transcriptional regulatory basis for multiple determinants of behavior. Proc Natl Acad Sci USA. 109:E1801-E1810.
- Greenberg J., Xia J., Zhou X., Thatcher S.R., Ament S.A., Newman T.C., Green P.J., Zhang W., Robinson G.E., and Ben-Shahar Y. (2012) Behavioral plasticity in honey bees is associated with differences in brain microRNA transcriptome. Genes Brain Behav. 11(6):660-670.
- Wheeler M.M., Ament S.A., Rodriguez-Zas S.M., and Robinson G.E. (2013) Brain gene expression changes elicited by peripheral vitellogenin knockdown in the honey bee. Insect Mol Biol. 22:562-573.
- Brownstein C.A., et al. (2014) An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results: The CLARITY Challenge. Genome Biol. 15(3):R53.
- Glusman G., Dhankani V., Robinson M., Farrah T., Mauldin D.E., Severson A., Stittrich A.B., Ament S.A., Roach J.C., Brunkow M.E., Bodian D.L., Vockley J.G., Shmulevich I., Niederhuber J.I., and Hood L. (2015) Identification of copy number variants in whole-genome data using Reference Coverage Profiles. Front Genet. 6:45.
- Wheeler M.M., Ament S.A., Rodriguez-Zas S.M., Southey B., and Robinson G.E. (2015) Diet and endocrine effects on behavioral maturation-related gene expression in the pars intercerebralis of the honey bee brain. J Exp Biol. 218:4005-4014.
- Bragg R.M., Coffey S.R., Weston R.M., Ament S.A., Cantle J.P., Minnig S., Funk C.C., Shuttleworth D.D., Woods E.L., Sullivan B.R., Jones L., Glickenhaus A., Anderson J.S., Anderson M.D., Dunnett S.B., Wheeler V.C., MacDonald M.E., Brooks S.P., Price N.D., and Carroll J.B. Motivational, proteostatic and transcriptional deficits precede synapse loss, gliosis and neurodegeneration in the B6.HttQ111/+ model of Huntington's disease. Submitted. Preprint: http://dx.doi.org/10.1101/081109
- Ament S.A.*, Pearl J.R.*, Grindeland A.*, St. Claire J., Earls J.C., Kovalenko M., Gillis T., Mysore J., Gusella J.F., Lee J.M., Kwak S., Howland D., Lee M., Baxter D., Scherler K., Wang K., Geman D., Carroll J.B., MacDonald M.E., Goodman N., Carlson G., Wheeler V.C., Price N.D., and Hood L.E.. High resolution time-course mapping of early transcriptomic, molecular and cellular phenotypes in Huntington’s disease CAG knock-in mice across multiple genetic backgrounds. Submitted.
Psychiatric disorders such as schizophrenia and bipolar disorder are strongly familial, with 8-10-fold relative risk in the first-degree relatives of probands. In the last few years, genoome-wide association studies have revealed >100 well-supported risk loci for psychiatric disorders, but the mechanisms by which these risk loci influence disease remain elusive, for at least two reasons. First, the effects of individual loci on risk for disease are very small (<1% relative risk). Second, most of the causal variants are non-coding, making it more difficult to determine their target genes.
Identifying rare risk variants can help characterize disease mechanisms, since these variants may have larger effects on disease risk and clearer effects on gene function than common variants discovered through GWAS. I was the lead author on one of the first whole-genome sequencing studies of bipolar disorder, identifying an enrichment of rare variants in neuronal ion channels (Ament et al., PNAS 2015). My lab is affiliated with several consortia generating large exome and genome sequencing datasets related to psychiatric disorders, including the Bipolar Genome Study, the Bipolar Sequencing Consortium, and the Anabaptist Sequencing Consortiun. Locally, we collaborate with the Program in Personalized and Genomic Medicine on genetics studies involving the Amish. The goal of all these studies is to identify rare variants, genes, and gene networks that influence risk for psychiatric disorders, as well as neurocognitive and neuroimaging endophenotypes.
Systems Biology of the Brain
Interpreting genomic data in the context of biological networks is another powerful strategy to discover disease mechanisms. We use cutting-edge informatics tools to analyze high-throughput genomic data in order to develop hypotheses about mechanisms of brain diseases. Recently, we have developed methods to reconstruct gene regulatory networks in the human and mouse brain, leveraging sequence motifs, epigenomic and transcriptomic data to predict the tissue-specific binding sites and target genes for hundreds of transcription factors. We are applying these methods to predict identify master regulator TFs in psychiatric and neurodegenerative diseases. We have validated several of these hypotheses through ChIP-seq and lentiviral overexpression of TFs in animal and cellular models. We are eager to collaborate with experimental groups generating new trancsriptomics and epigenomic datasets.
Patient-derived, induced pluripotent stem cells (iPSCs) and iPSC-derived neurons are a promising system in which to characterize phenotypes associated with the genetic variation underlying human disease. In collaboration with Elliot Hong (Psychiatry) and Francis McMahon (NIMH), my lab is developing a resource of iPSCs from Amish families with psychiatric disorders. These families have been extensively characterized for neuroimaging and neurocognitive phenotypes, creating a unique cohort in which to link genetic variation to cellular, brain, and behavior phenotypes. We will use these cell lines to test two hypotheses emerging from psychiatric genetics and systems biology studies. First, we hypothesize that psychiatric disorders involve neurodevelopmental changes in gene regulation. Second, we hypothesize that psychiatric disorders involve synaptic changes inducing neuronal hyperexcitability. Both mechanisms are predicted to alter the structure and function of the adult brain, perhaps in subtle ways.We will test each hypothesis by characterizing the functions of specific risk variants found in Amish families.