Skip to main content

Seth A. Ament, PhD

Academic Title:

Assistant Professor

Primary Appointment:

Psychiatry

Additional Title:

Faculty Member, Institute for Genome Sciences; Faculty Member, Maryland Psychiatric Research Center

Location:

670 West Baltimore Street Baltimore, MD 21201

Phone (Primary):

(410) 706-5681

Education and Training

Ph.D. University of Illinois at Urbana-Champaign (Neuroscience, 2010)

A.B. Harvard University (Biology, 2003)

Biosketch

My research focuses on genetic and genomic studies of the brain and brain disorders through four strategies: (1) genome sequencing studies to identify rare mutations that increase risk for brain disorders, and functional studies of these mutations in human stem cells and animal models; (2) single-cell transcriptomics and epigenomics studies to characterize the diversity of cell types in the brain and how these populations of cells are altered in brain disorders; (3) molecular and computational systems biology studies integrating GWAS and functional genomics data from the mammalian brain to characterize disease-perturbed gene networks and multi-scale disease mechanisms; and (4) translational studies designed to leverage genomic data for the development of clinically useful biomarkers and novel therapeutic targets. Ongoing studies in the lab apply these approaches to mood disorders, schizophrenia, substance use disorders, Huntington's disease, neuroinflammation, and hearing loss. Our work is highly collaborative, both locally and as part of large consortia, including the BRAIN Initiative Cell Census Network and the Whole Genome Sequencing of Psychiatric Disorders consortium.

 

Research/Clinical Keywords

Bipolar disorder; schizophrenia; genetics; genomics; systems biology; stem cells; neuron; brain; behavior

Highlighted Publications

  1. Pearl J.R., Colantuoni C., Bergey D.E., Funk C.C., Basu B., Casella A.M., Oshone R., Shannon P., Hood L., Price N.D., Ament S.A. (2019) Genome-scale transcriptional regulatory network models of psychiatric and neurodegenerative disorders. Cell Systems. 8(2):122-135.e7
  2. 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. (2018) Genome-scale transcriptional regulatory network models for the mouse and human striatum predict roles for SMAD3 and other transcription factors in Huntington's disease. Mol. Systems Biol. 14(3):e7435. 
  3. 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.
  4. 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.

Additional Publication Citations

 

  • Ament S.A., Bullis R., Hanlon R.T., and Mensinger A. (1997) Righting response and escape response in Opsanus tau are temperature dependent. Biol Bull 193:265-266.

 

  1. 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.
  2. 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.
  3. Honeybee Genome Sequencing Consortium (2006) Insights into social insects from the genome of the honeybee Apis mellifera. Nature 443:931-49.
  4. 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.
  5. 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.
  6. Brockmann A. Annangudi P., Richmond T.A., Ament S.A., Xie F., Southey B.R., Rodriguez-Zas S.R., SweedlerJ.V., and Robinson G.E. (2009) Quantitative peptidomics reveal brain peptide signatures of behavior. Proc Natl Acad Sci USA. 106:2383-2388.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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. (2017) Motivational, proteostatic and transcriptional deficits precede synapse loss, gliosis and neurodegeneration in the B6.HttQ111/+ model of Huntington's disease. Scientific Reports. 7:41570.
  21. Ament 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. (2017) High resolution time-course mapping of early transcriptomic, molecular and cellular phenotypes in Huntington’s disease CAG knock-in mice across multiple genetic backgrounds. Human Mol Genet. 26(5):913-922.
  22. Bruce H.A., Kochunov P., Paciga S.A., Hyde C.L., Chen X., Xie Z., Zhang B., Xi H.S., O’Donnell P., Whelan C., Schubert C.R., Bellon A., Ament S.A., Shukla D.K., Du X., Rowland L.M., O’Neill H., Hong L.E. (2017) Potassium channel gene associations with joint processing speed and white matter impairments in schizophrenia. Genes Brain Behav. 16(5):515-521.
  23. Coffey S.R., Bragg R.M., Minnig S., Ament S.A., Glickenhaus A., Shelnut D., Carrillo J.M., Shuttleworth D.D., Rodier J.-A., Noguchi K., Bennett C.F., Price N.D., Kordasiewicz J.B., Carroll J.B. (2017) Peripheral Htt silencing does not ameliorate central signs of disease in the B6.HttQ111/+ mouse model of Huntington’s disease. PLoS One. 12(4): e0175968.
  24. Ryan M., Kochunov P., Rowland L.M., Mitchell B.D., Wijtenburg S.A., Fieremans E., Veraart J., Novikov D.S., Du X., Adhikari B., Fisseha F., Bruce H., Chiappelli J., Sampath H., Ament S., O'Connell J., Shuldiner A.R., Hong L.E. (2017) Lipid Metabolism, Abdominal Adiposity, and Cerebral Health in the Amish. 25(11):1876-1880.
  25. 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. (2018) Transcriptional regulatory networks underlying gene expression changes in Huntington's disease. Systems Biol. 14(3):e7435.
  26. Zekavat S.M., Ruotsalainen S., Handsaker R.E., Alver M., Bloom J., Poterba T., Seed C., Ernst J., Chaffin M., Engreitz J., Peloso G.M., Manichaikul A., Yang C., Ryan K.A., Fu M., Johnson W.C., Tsai M., Budoff M., Vasan R.S., Cupples L.A., Rotter J.I., Rich S.S., Post W., Mitchell B.D., Correa A., Metspalu A., Wilson J.G., Salomaa V., Kellis M., Daly M.J., Neale B.M., McCarroll S., Surakka I., Esko T., Ganna A., Ripatti S., Kathiresan S., Natarajan P., NHLBI TOPMed Lipids Working Group (2018) Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries. Nat Commun. 9(1):2606.
  27. Natarajan P., Peloso G.M., Zekavat S.M., Montasser M., Ganna A., Chaffin M., Khera A.V., Zhou W., Bloom J.M., Engreitz J.M., Ernst J., O'Connell J.R., Ruotsalainen S.E., Alver M., Manichaikul A., Johnson W.C., Perry J.A., Poterba T., Seed C., Surakka I.L., Esko T., Ripatti S., Salomaa V., Correa A., Vasan R.S., Kellis M., Neale B.M., Lander E.S., Abecasis G., Mitchell B., Rich S.S., Wilson J.G., Cupples L.A., Rotter J.I., Willer C.J., Kathiresan S.; NHLBI TOPMed Lipids Working Group (2018) Deep-coverage whole genome sequences and blood lipids among 16,324 individuals. Nat Commun. 9(1):3391.
  28. Glahn D.C., Nimgaonkar V.L., Raventós H., Contreras J., McIntosh A.M., Thomson P.A., Jablensky A., McCarthy N.S., Blackburn N.B., Peralta J.M., Knowles E.M., Mathias S.R., Ament S.A., McMahon F.J., Gur R.C., Bucan M., Curran J.E., Almasy L., Gur R.E., Blangero J. (2019) Rediscovering the Value of Families for Psychiatric Genetics Research. Molecular Psychiatry. 24(4):523-535.
  29. Budde M., Friedrichs S., Alley-Rodriguez N., Ament S.A., Badner J.A., Berrettini W.H., Byerley W., Cichon S.,Comes A.L., Coryell W., Craig D.W., Degenhardt F., Edenberg H.J., Foroud T., Forstner A.J., Frank J., Gershon E.S., Goes F.S., Greenwood T.A., Hipolito M., Hood L., Koller D.L., Lawson W.B., Liu C., McInnis M.G., McMahon F.J., Meier S.M., Mühleisen T.W., Nievergelt C.M., Nurnberger J.I., Nwulia E.A., Potash J.B., Quarless D., Rice J., Roach J.C., Scheftner W.A., Schork N.J., Shekhtman T., Shilling P.D., Streit F.S., Strohmaier J., Szelinger S., Treutlein J., Witt S.H., Zandi P.P., Bickeböller H,, Falkai P.G., Kelsoe J.R., Nöthen M.M., Rietschel M., Schulze T.G., Malzahn D. (2019) Efficient genomic region-based testing uncovers genetic risk factors for inter-episode functional outcome in bipolar disorder. European Journal of Neuropsychiatry. 29(1):156-170.
  30. Pearl J.R., Colantuoni C., Bergey D.E., Funk C.C., Basu B., Casella A.M., Oshone R., Shannon P., Hood L., Price N.D., Ament S.A. (2019) Genome-scale transcriptional regulatory network models of psychiatric and neurodegenerative disorders. Cell Systems. 8(2):122-135.e7
  31. Bruce H.A., Kochunov P., Mitchell B., Strauss K.A., Ament S.A., Rowland L.M., Du X., Fisseha F., Kavita T., Chiappelli J., Wisner K., Sampath H., Chen S., Kvarta M.D., Seneviratne C., Postolache T.T., Bellon A., McMahon F.J., Shuldiner A., Hong L.E. (2019) Clinical and Genetic Validity of Quantitative Bipolarity. Transl. 9(1):228
  32. Kessler M.D., Loesch D.P., Perry J.A., Heard-Costa N.L., Taliun D., Cade B.E., Wang H., Daya M., Ziniti J., Datta S., Celedón J.C., Soto-Quiros M.E., Avila L., Weiss S.T., Barnes K., Redline S.S., Vasan R.S., Johnson A.D., Mathias R.A., Hernandez R., Wilson J.G., Nickerson D.A., Abecasis G., Browning S.R., Zöllner S., O'Connell J.R., Mitchell B.D., National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Population Genetics Working Group, O'Connor T.D. (2020) De novo mutations across 1,465 diverse genomes reveal mutational insights and reductions in the Amish founder population. Proc Natl Acad Sci U S A. 117(5): 2560-2569.
  33. Chan J.C., Morgan C.P., Leu N.A., Shetty A., Cisse Y.M., Nugent B.M., Morrison K.E., Jašarević E., Huang W., Kanyuch N., Rodgers A.B., Bhanu N.V., Berger D., Garcia5 B.A., Ament S.A., Kane M., Epperson C.M., Bale T.L. (2020) Reproductive tract extracellular vesicles are sufficient to transmit intergenerational stress and program neurodevelopment. Nature Commun. 11:1499.Published Multimedia

Preprints

  1. Kalra G., Milon B.,  Casella A.M., Song Y., Herb B.R., Rose K.P., Hertzano R., Ament S.A. Biological insights from multi-omic analysis of 31 genomic risk loci for adult hearing difficulty bioRxiv.. https://doi.org/10.1101/562405
  2. Ziffra R.S., Kim C.N., Wilfert A., Turner T.N., Haeussler M., Casella A.M., Przytycki P.F., Kreimer A., Pollard K.S., Ament S.A., Eichler E.E., Ahituv N., Nowakowski T.J. Single cell epigenomic atlas of the developing human brain and organoids. bioRxiv. https://doi.org/10.1101/2019.12.30.891549
  3. Yao Z.*, Liu H.*, Xie F.*, Fischer S.*, et al. … BRAIN Initiative Cell Census Network (BICCN), Zeng H., Mukamel E.A. 2020. An integrated transcriptomic and epigenomic atlas of mouse primary motor cortex cell types. In review at (Preprint: bioRxiv. https://doi.org/10.1101/2020.02.29.970558)
  4. Bakken T.E. … Lein E.S. Evolution of cellular diversity in primary motor cortex of human, marmoset monkey, and mouse. bioRxiv. https://doi.org/10.1101/2020.03.31.016972
  5. Pearl J.R.#, Shetty A.C.#, Cantle J.P., Bergey D.E., Bragg R.M., Coffey S.R., Kordasiewicz H.B., Hood L., Price N.D., Ament S.A.*, Carroll J.B.*. Altered Huntingtin-chromatin interactions predict transcriptional and epigenetic changes in Huntington’s disease. https://doi.org/10.1101/2020.06.04.132571
  6. Malaiya S., Cortes-Gutierrez M., Herb B.R., Coffey S.R., Legg S.R.W., Cantle B.P., Carroll J.B., Ament S.A. Single-nucleus RNA-seq reveals dysregulation of striatal cell identity due to Huntington’s disease mutations. bioRxiv.

 

Research Interests

Psychiatric Genetics

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.

Transcriptional Regulatory Networks in the Mammalian 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, and using CRISPR/Cas9 genome editing. We are eager to collaborate with experimental groups generating new trancsriptomics and epigenomic datasets. Current projects aim to elucidate gene regulatory networks in psychiatric disorders, Huntington's disease, hearing loss, and brain development.

Stem Cells

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.