• PhD, University of Illinois at Urbana-Champaign, Neuroscience, 2010
• AB, Harvard University, Biology, 2003

My research group conducts basic and translational studies to discover genomic and neurobiological mechanisms and advance precision medicine for brain disorders. Ongoing studies apply four strategies to psychiatric disorders, substance use disorders, and neurological conditions:

1) We develop and apply single-cell and spatial multimodal technologies to characterize cell type diversity and disease-associated transcriptomic and epigenomic changes in many regions of the human and mammalian brain.

2) We conduct genome-sequencing and genome-wide association studies to identify risk variants for these disorders.

3) We use human stem cell derived brain organoid and neural cell models to test mechanistic hypotheses emerging from our high-throughput genomic studies.

4) We work with clinical collaborators to build patient cohorts that leverage these genetic and genomic tools for the development of precision biomarkers and therapies.

Lab website: amentlab.org

Psychiatric disorders, substance use disorders, genomics, neurobiology, stem cells

Rare Variants in Neuropsychiatry

Hasin N., Riggs L.M., Shekhtman T., Ashworth J., Lease R., Oshone R.T., Humphries E., Badner J., Thompson P., Glahn D.C., Craig D.W., Edenberg H.J., Gershon E., McMahon F.J., Nurnberger J.I., Zandi P.P., Kelsoe J.R., Roach J.C., Gould T.D., and Ament S.A. (2021) Rare variants implicate NMDA receptor signaling and cerebellar gene networks in risk for bipolar disorder. medRxiv. doi:10.1101/2021.06.02.21258261

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.

Single-Cell Genomics

Herb B.R., Glover H.J., Bhaduri A., Casella A.M., Bale T.L., Kriegstein A.R., Doege C.A., Ament S.A. Single-cell genomics reveals region-specific developmental trajectories underlying neuronal diversity in the prenatal human hypothalamus. bioRxiv. https://doi.org/10.1101/2021.07.20.453090

Adkins R.S. et al. (along with the BRAIN Initiative Cell Census Network, including Ament S.A.). A multimodal cell census and atlas of the mammalian primary motor cortex. bioRxiv. doi: https://doi.org/10.1101/2020.10.19.343129

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. doi: https://doi.org/10.1101/2019.12.30.891549

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. J Neurosci. JN-RM-2074-20; DOI: https://doi.org/10.1523/JNEUROSCI.2074-20.2021.

Network Biology

Casella A.M., Colantuoni C., Ament S.A. Regulome-wide association study identifies enhancer properties associated with risk for schizophrenia. bioRxiv. https://doi.org/10.1101/2021.06.14.448418

Funk C.C.*, Casella A.M.*, Jung S., Richards M., Rodriguez A., Shannon P., Donovan R., Heavner B., Chard K., Xiao Y., Glusman G., Erleskin-Taner N., Golde T., Toga A., Hood L., Van Horn J.D., Kesselman C., Foster I., Madduri R., Price N.D., Ament S.A. (2020) Atlas of Transcription Factor Binding Sites from ENCODE DNase Hypersensitivity Data Across 27 Tissue Types. Cell Reports. 32(7):108029.

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

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.

Peer-reviewed journal articles

Note: For all publications, * is used to indicate equal contributions, while # is used to indicate corresponding authors.

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.

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.

Smith A.B. et al. (along with the Honeybee Genome Sequencing Consortium, including Ament S.A.] (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. Annangudi P., Richmond T.A., Ament S.A., Xie F., Southey B.R., Rodriguez-Zas S.R., Sweedler J.V., and Robinson G.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.

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.*, 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.

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.

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., Beggs A.H., Homer N., Merriman B., Yu T.W., Flannery K.C., DeChene E.T., Towne M.C., Savage S.K., Price E.N., Holm I.A., Luquette L.J., Lyon E., Majzoub J., Neupert P., McCallie D., Szolovits P., Willard H.F., Mendelsohn N.J., Temme R., Finkel R.S., Yum S.W., Medne L., Sunyaev S.R., Adzhubey I., Cassa C.A., De Bakker P.I.W., Duzkale H., Dworzyński P., Fairbrother W., Francioli L., Funke B.H., Giovanni M.A., Handsaker R.E., Lage K., Lebo M.S., Lek M., Leshchiner I., Macarthur D.G., Rehm H.L., Soemedi R., Stitziel N.O., Vestecka S., Supper J., Gugenmus C., Klocke B., Hahn A., Schubach M., Menzel M., Biskup S., Freisinger P., Deng M., Braun M., Perner S., Smith R.J.H., Andorf J.L., Huang J., Ryckman K., Sheffield V.C., Stone E.M., Bair T., Black-Ziegelbein E.A., Braun T.A., Darbro B., DeLuca A.P., Kolbe D.L., Scheetz T.E., Shearer A.E., Sompallae R., Wang K., Bassuk A.G., Edens E,, Mathews K., Moore S.A., Shchelochkov O.A., Trapane P., Bossler A., Campbell C.A., Heusel J.W., Kwitek A., Maga T., Panzer K., Wassink T., Van Daele D., Azaiez H., Booth K., Meyer N., Segal M.M., Williams M.S., Tromp G., White P., Corsmeier D., Fitzgerald-Butt S., Herman G., Lamb-Thrush D., McBride K.L., Newsom D., Pierson C.R., Rakowsky A.T., Maver A., Lovrečić L., Palandačić A., Peterlin B., Torkamani A., Wedell A., Huss M., Alexeyenko A., Lindvall J.M., Magnusson M., Nilsson D., Stranneheim H., Taylan F., Gilissen C., Hoischen A., Van Bon B., Yntema H., Nelen M., Zhang W., Sager J., Zhang L., Blair K., Kural D., Cariaso M., Lennon G.G., Javed A., Agrawal S., Ng P.C., Sandhu K.S., Krishna S., Veeramachaneni V., Isakov O., Halperin E., Friedman E., Shomron N., Glusman G., Roach J.C., Caballero J., Cox H.C., Mauldin D., Ament S.A., Rowen L., Richards D.R., San Lucas F.A., Gonzalez-Garay M.L., Caskey C.T., Bai Y., Huang Y., Fang F., Zhang Y., Wang Z., Barrera J., Garcia-Lobo J.M., González-Lamuño D., Llorca J., Rodriguez M.C., Varela I., Reese M.G., De La Vega F.M., Kiruluta E., Cargill M., Hart R.K., Sorenson J.M., Lyon G.J., Stevenson D.A., Bray B.E., Moore B.M., Eilbeck K., Yandell M., Zhao H., Hou L., Chen X., Yan X., Chen M., Li C., Yang C., Gunel M., Li P., Kong Y., Alexander A.C., Albertyn Z.I., Boycott K.M., Bulman D.E., Gordon P.M.K., Innes A.M., Knoppers B.M., Majewski J., Marshall C.R., Parboosingh J.S., Sawyer S.L., Samuels M.E., Schwartzentruber J., Kohane I.S., Margulies D.M. (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.

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.

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. (2017) Motivational, proteostatic and transcriptional deficits precede synapse loss, gliosis and neurodegeneration in the B6.Htt^Q111/+ model of Huntington's disease. Scientific Reports. 7:41570.

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.

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.

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.Htt^Q111/+ mouse model of Huntington’s disease. PLoS One. 12(4): e0175968.

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.

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.

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.

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.

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

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

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. Nat Commun. 11:1499.

Funk C.C.*,  Casella A.M.*, Jung S., Richards M., Rodriguez A., Shannon P., Donovan R., Heavner B., Chard K., Xiao Y., Glusman G., Erleskin-Taner N., Golde T., Toga A., Hood L., Van Horn J.D., Kesselman C., Foster I., Madduri R.#, Price N.D.#, Ament S.A.# Atlas of Transcription Factor Binding Sites from ENCODE DNase Hypersensitivity Data Across 27 Tissue Types. Cell Reports. 32 (7): 108029.

Kalra G., Milon B.,  Casella A.M., Song Y., Herb B.R., Rose K.P., Hertzano R., Ament S.A. (2020) Biological insights from multi-omic analysis of 31 genomic risk loci for adult hearing difficulty. PLoS Genet. 16(9): e1009025.

Morgan C.P., Shetty A.C., Chan J.C., Berger D.S., Ament S.A., Epperson C.N., Bale T.L. (2020) A within- and between-subject modeling of the human sperm transcriptome identifies dynamic and stress-responsive sncRNAs. Scientific Reports. 10(1):1-20.

Bruce H., Kochunov P., Chiappelli J., Savransky, T., Scarino K., Sewell J., Marshall W., Kvarta M., McMahon F.J., Ament S.A., Postolache T., O’Connell J., Shuldiner A., Mitchell B., Hong L.E. (2021) Genetic vs. Stress and Mood Determinants of Sleep in the Amish. Am J Med Genet B: Neuropsych Genet.

Kvarta M., Bruce H., Chiappelli J., Hare S., Dr. Goldwaser E., Sewell J., Sampath H., Lightner S., Marshall W., Hatch K., Humphries E., Ament S., Shuldiner A., Mitchell B., McMahon F., Kochunov P., Hong L.E. (2021) Multidimensional Stress vs. Genetics in Depression. Translational Psychiatry. 11(1):254.

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. J Neurosci. JN-RM-2074-20; DOI: https://doi.org/10.1523/JNEUROSCI.2074-20.2021.

Orvis J., Gottfried B., Kancherla J., Adkins R.S., Song Y., Dror A.A., Olley D., Rose K., Chrysostomou E., Kelly M.C., Milon B., Matern M.S., Azaiez H., Herb B., Colantuoni C., Carter R.L., Ament S.A., Kelley M.W., White O., Corrada Bravo H., Mahurkar A., Hertzano R. gEAR: gene Expression Analysis Resource portal for community-driven, multi-omic data exploration. Nat Methods. 18(8):843-844. doi: 10.1038/s41592-021-01200-9

Bakken T.E., Jorstad N.L., Hu Q., Lake B.B., Tian W., Kalmbach B.E., Crow M., Hodge R.D., F.M., Sorensen S.A., Eggermont J., Yao Z., Aevermann B.D., Aldridge A.I., Bartlett A., Bertagnolli D., Casper T., Castanon R.G., Crichton K., Daigle T.L., Dalley R., Dee N., Dembrow N., Diep D., Ding S.-L., Dong W., Fang R., Fischer S., Goldman M., Goldy J., Graybuck L.T., Herb B.R., Hou X., Kancherla J., Kroll M., Lathia K., van Lew B., Li Y.E., Liu C.S., Liu H., Mahurkar A., McMillen D., Miller J.A., Moussa M., Nery J.R., Orvis J., Owen S., Palmer C.R., Pham T., Plongthongkum N., Poirion O., Reed N.M., Rimorin C., Rivkin A., Romanow W.J., Sedeño-Cortés A.E., Siletti K., Somasundaram S., Sulc J., Tieu M., Torkelson A., Tung H., Wang X., Xie F., Yanny A.M., Zhang R., Ament S.A., Corrada Bravo H., Chun J., Dobin A., Gillis J., Hertzano R., Hof P.R., Höllt T., Horwitz G.D., Keene C.D., Kharchenko P.V., Ko A.L., Lelieveldt B.P., Luo C., Mukamel E.A., Preissl S., Regev A., Ren B., Scheuermann R.H., Smith K., Spain W.J., White O.R., Koch C., Hawrylycz M., Tasic B., Macosko E.Z., McCarroll S.A., Ting J.T., Zeng H., Zhang K., Feng G., Ecker J.R., Linnarsson S., Lein E.S. Comparative cellular analysis of motor cortex in human, marmoset, and mouse. In press. (Preprint: bioRxiv. https://doi.org/10.1101/2020.03.31.016972)

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. In press.

Adkins R.S. et al. (along with the BRAIN Initiative Cell Census Network, including Ament S.A.). A multimodal cell census and atlas of the mammalian primary motor cortex. In press.

• Yao Z.*, Liu H.*, Xie F.*, Fischer S.*, et al (along with the BRAIN Initiative Cell Census Network, including Ament S.A.). An integrated transcriptomic and epigenomic atlas of mouse primary motor cortex cell types. In press.

Single-Cell and Spatial Multi-omics

The laboratory develops and applies single-cell and spatial multi-omic technologies to understand the cellular organization of the nervous system and its disruption in disease states. A central premise of our research is that the remarkable complexity of the brain arises from the diversity of its constituent cell types and dynamic cellular states. We use single-cell transcriptomic, epigenomic, and multimodal profiling to discover previously unrecognized neuronal and glial populations, define developmental trajectories, characterize cell-state transitions, and reconstruct the gene regulatory networks that govern brain development, circuit maturation, and neural plasticity. Complementary spatial transcriptomic approaches place molecularly defined cell populations within their native tissue architecture, enabling studies of cellular interactions, circuit organization, and regional specialization. In parallel, we develop new experimental and computational methods that integrate molecular measurements with complementary phenotypes, including neuronal morphology, physiology, connectivity, and genetic perturbations. to generate comprehensive multimodal descriptions of individual cells. Together, these approaches provide a powerful framework for understanding fundamental principles of brain organization while revealing the cellular mechanisms disrupted in neurological and psychiatric disorders.

Genome Sequencing and Human Genetics

The laboratory uses genome sequencing and human genetic approaches to identify risk genes and molecular mechanisms underlying neuropsychiatric disease susceptibility and treatment responses. A major focus is the study of founder populations, particularly the Old Order Amish, and multiplex families with multiple affected individuals, where extended pedigrees and enriched inheritance patterns facilitate discovery of rare, high-impact genetic variants. Deep phenotyping in these cohorts enables us to characterize mediating effects of population-specific risk variants on neuroimaging, neurocognitive, and behavioral tratis. These studies complement analyses of large case-control cohorts, including our contributions to large national and international collaborative genomics initiatives. By integrating genome sequencing, genome-wide association studies, polygenic risk analyses, and functional genomic annotation, we use human genetics as a foundation for identifying biological pathways, prioritizing disease genes, and generating mechanistic hypotheses that can be tested experimentally.

Stem Cell Models and Functional Genomics

Human induced pluripotent stem cell (iPSC) models provide a versatile platform for investigating the functional consequences of disease-associated genetic variation in experimentally controlled systems. The laboratory develops scalable neuronal, glial, and brain organoid models that recapitulate key aspects of human brain development and enable quantitative analyses of cellular differentiation, synapse formation, neuronal morphology, physiology, and gene regulation. We combine these model systems with high-content imaging, single-cell and spatial multi-omics, and CRISPR-based genome engineering to systematically investigate gene function and molecular pathways implicated in neuropsychiatric disease. These technologies provide an important bridge between human genetic discovery and mechanistic understanding.

Clinical and Translational Cohorts

The laboratory collaborates closely with clinicians and physician-scientists to establish deeply phenotyped patient cohorts that connect molecular biology with human disease. These studies integrate genomic, transcriptomic, neuroimaging, biomarker, neurocognitive, physiological, and longitudinal clinical data to investigate disease mechanisms across the lifespan. Our translational research strategy emphasizes bidirectional discovery: observations from patient cohorts generate hypotheses that are tested experimentally in cellular and animal models, while mechanistic discoveries from experimental systems are evaluated in human populations for their relevance to disease biology. By combining large-scale clinical datasets with state-of-the-art molecular technologies, we seek to identify biomarkers of disease risk and progression, improve patient stratification, and accelerate the development of precision medicine approaches for neurological and psychiatric disorders.

Human brain development and its alterations in neurodevelopmental and neuropsychiatric disorders

• A BRAIN Initiative Resource: The Neuroscience Multi-omic Data Archive. NIH/NIMH, R24 MH114788, 9/15/17 – 7/31/27 (Owen White, PI)
  
  • The NeMO Archive serves as the genomics data archive for the BRAIN Initiative. We build infrastructure for the BRAIN Initiative Cell Atlas Network and contribute to atlases for cell type diversity in the developing and adult brain.
• Multi-scale consequences of variants in the neuropsychiatric risk gene SETD1A in a population isolate. NIH/NIMH, R01 MH129343, 8/15/22 – 5/31/27 (Seth Ament, PI)
  
  • This R01 supports collaborative studies with the Amish Research Program to investigate population-enriched variants in the Old Order Amish founder population and their clinical, cellular, and genomic mechanisms.
• Endocannabinoids Regulate Microglia in Developing Brain. NIH/NIDA, R01 DA039062, 6/1/22 – 5/31/27 (Peg McCarthy, PI)
• Neuroinflammation, Epigenetics and Male Vulnerability. NIH/NIMH, 2 R01 MH052716, 7/1/22 – 6/30/27 (Peg McCarthy, PI)
  
  • These collaborative projects with Dr. Peg McCarthy, a leading expert on neuroimmunology and sex differences in the brain, investigate roles for immune cells in brain development, primarily using rat models. 
• The role of NPRL2 loss in focal cortical dysplasia. NIH/NINDS, R01 NS131223, 4/15/23 – 3/31/28 (Phil Iffland, PI)
  • Many mutations in the mTOR pathway cause neurodevelopmental disorders characterized by malformations of cortical development and autistic and epileptic features. This R01 with Phil Iffland investigates mutations in one such mTORopathy, focal cortical dysplasia resulting from mutations in Nprl2, using a mouse model. The Ament lab is collaborating on spatial transcriptomic studies to investigate molecular mechanisms underlying cortical dyslamination in this model and the ability to rescue these developmental changes via mTOR inhibition.
• Internal dynamics of the post-synaptic density. NIH/NIMH, R37 MH080046, 11/18/24 – 8/31/29 (Tom Blanpied, PI)
  • The Blanpied Lab studies the structure and function of synapses in the mammalian brain using super-resolution microscopy and live-cell imaging of single synapses. AI-based analyses of these data yield high-dimensional data describing the features of many thousands of synapses. We are collaborating with Tom's lab to analyze these data to describe synaptic diversity and the structure features that predict differences in function.
• Dissecting the role of Ca2+ channel dysfunction in the pathogenesis of neurodevelopmental disorders. NIH/NIMH, R01MH137160, 4/1/25 – 3/31/30 (Ivy Dick, PI)
  • Mutations in the L-type voltage gated calcium channel (CaV 1.2, CACNA1C) cause Timothy syndrome, a developmental disorder associated with autistic features, as well as heart arhythmia. This R01 with Ivy Dick investigates physiological mechanisms, using both iPSCs and mouse models. We are using Patch-seq, snRNA-seq, and spatial multimodal profiling of neurons with Timothy syndrome mutations to understand their cell type-specific molecular mechanisms.
• Convergent effects of genetic and inflammatory risk factors for autism spectrum disorders on the development of human Purkinje cells. MSCRF, 2025-R2-MSCRFD-00029, 7/1/25 – 6/30/27 (Seth Ament, PI)
  • This project develops a human cerebellar organoid model to understand how genetic and immune risk factors for autism spectrum disorder converge on the development of the cerebellum.
• A Human Neurodevelopmental Model for Investigating the role of STRADA in Inhibitory Neuron Cortical Lamination and Epilepsy. MSCRF, 7/1/25 – 6/30/27 (Whitney Parker, PI)
  • Loss-of-function mutations in STRADA cause mTOR hyperactivation, cortical dyslamination, and epilepsy. Dr. Whitney Parker is a pediatric neurosurgeon and surgeon-scientist who treats patients with epilepsy in her clinical practice. This study investigates the effects of STRADA mutations on the development and migration of inhibitory neurons, using patient-derived iPSCs.
• Quantifying cerebellar multi-omic and synaptic features in autism spectrum disorders. NIH/NIMH, R01 MH139606, 4/1/26 – 12/30/30 (Seth Ament and Tom Blanpied, PIs)
  • Changes in synapses and neuronal connectivity are through to be core mechanisms underlying neuropsychiatric and neurodevelopmental disorders, yet there have been almost no direct measurements of synapses in the brains of humans with NDDs. This collaboration with Tom Blanpied's lab combines spatial transcriptomics and super-resolution STED microscopy to investigate coordinated changes in cell type-specific gene expression and synaptic structure in post-mortem brains of donors with autism and related disorders, leveraging unique brain tissue resources from the University of Maryland Baltimore Brain and Tissue Biobank.
• High-throughput spatial multimodal genetic screens in human and mouse neurons. MSCRF, 2026-MSCRFD-6688, 7/1/26 – 6/30/28 (Seth Ament, PI)
  • The goal of this study -- a collaboration with Tom Blanpied and Wei Li -- is to develop new high-throughput approaches to co-assay transcriptomic, morphological, and physiological characteristics of thousands of cultured neurons in parallel. This technology also enables multimodal genetic screens by co-culturing neurons from multiple human donors (cell villages) or with many distinct engineered mutations (spatial Perturb-seq).

Genomic mechanisms of substance use disorders and addiction

• Genomic profiling mediating the protective effect of social reward on opioid craving. NIH/NIDA, R01 DA056440, 8/1/22 – 6/30/27 (Marco Venniro, Mary Kay Lobo, and Seth Ament, PIs)
  
  • Social environments strongly influence patterns of substance use and relapse. In an animal model developed by our collaborator, Dr. Marco Venniro, rats given the opportunity to interact with a social partner display reduced behavioral signs of opioid craving. This study aims to characterize genomic and neural circuit mechanisms mediating these protective effects. 
• Lasting Neurological Effects of Perinatal Opioids. NIH/NIDA, 1R01DA054905, 9/30/22 – 7/31/27 (MK Lobo, Asaf Keller, and Seth Ament, PIs)
  
  • The opioid epidemic has led to dramatically higher rates of opioid use during pregnancy. Infants exposed to opioids during pregnancy display withdrawal signs after birth and are at risk for a wide range of adverse neurological outcomes that persist through childhood. Drs. Mary Kay Lobo and Asaf Keller developed a mouse model for perinatal fentanyl exposure. In this R01, we are using this model to investigate the persistent effects of perinatal fentanyl on the development of the cortex and striatum. Parallel studies in the Ament lab investigate genetic and genomic factors associated with withdrawal severity in opioid-exposed infants, a collaboration with Dr. Dina Metwally and the Neonatal Intensive Care Unit at the University of Maryland Medical Center. We are also developing a human iPSC-derived model for the effects of opioids on neurodevelopment and physiology
• NeMO Archive: SCORCH Support, Coordination and Outreach. NIH/NIDA, UM1 DA052244, 8/1/25 – 6/30/30 (Owen White, Anup Mahurkar, and Seth Ament, PIs)
  
  • The Single-Cell Opioid Responses in the Context of HIV (SCORCH) consortium aims to characterize molecular adaptations associated with substance use disorders, as well as the effects of comorbid HIV infections, spanning multiple brain regions in humans and animal models. The NeMO-SCORCH Data Coordination Center establishes the consortium's data infrastructure and leads working groups toward a joint analysis of the entire data compendium. It has been a privilege to collaborate with Dr. Owen White and Anup Mahurkar on the development of NeMO projects for many years.
• Joint decomposition of SCORCH mulit-omic data to explore the impact of SUD and HIV on reward circuitry and neuroinflammation. NIH/NIDA, R01 DA063090, 9/1/25 – 5/31/30  (Brian Herb and Carlo Colantuoni, PIs)
  
  • The SCORCH program is supporting several R01s for joint analysis of genomic and clinical data produced by the consortium. This project led by IGS faculty Brian Herb and Carlo Colantuoni is applying innovative data decomposition techniques to characterize gene networks influenced by opioids and other addictive substances across hundreds of genomic datasets. The project also supports the development of web resources for the visualization and analysis of these gene networks using the NeMO Analytics platform.

Brain injury and neurodegeneration

• Bidirectional Brain-Gut interactions, chronic neuroinflammation and neurodegeneration after traumatic brain injury. NIH/NINDS, R01 NS124687, 8/1/22 – 7/31/27 (Bogdan Stoica, PI)
• NOX2 drives microglia-dependent neurodegeneration after traumatic brain injury. NIH/NINDS, R01 NS129094, 8/1/22 – 7/31/27 (Bogdan Stoica, PI)
  
  • We collaborate with Bogdan Stoica and other researchers in the Center for Shock Trauma and Anesthesiology Research to investigate genomic mechanisms underlying recovery from traumatic and non-traumatic brain injuries.

nemoarchive.org

• Neuroscience Multi-Omic Archive
• NeMO Analytics

Single-Cell Opioid Responses in the Context of HIV Consortium (scorch.igs.umaryland.edu)

Ament Lab Website (amentlab.org)