Andre M. Sousa, PhD

Member of the SCRMC Neural Regeneration Focus Group

Research Description:

The broad goals of our research program are to identify and characterize the molecular and cellular mechanisms that govern human brain development and evolution, and to apply that knowledge towards understanding neuropsychiatric and neurodevelopmental disorders.

We apply a multifaceted approach that combines: 1) genomic studies to identify the genes and the regulatory elements that control their expression, thus elucidating human-specific aspects of brain development; 2) developmental neurobiology studies to characterize the functions of those candidate genes in the development of the brain; 3) molecular and cellular biology studies that inform the mechanisms that are disrupted by alterations in those genes, particularly the ones that are associated to neurodevelopmental and neuropsychiatric disorders.

To achieve these goals, since the human brain is not amenable to direct experimentation, we use a combination of human postmortem tissue, mouse genetic models, and in in vitro cultures, such as primary cells, neuroepithelial stem cells, iPS cells, and organotypic slices.

Selected References: 

1. Liu J, Mosti F, Zhao H, Sotelo-Fonseca J, Escobar-Tomlienovich C, Lollis D, Musso CM, Mao Y, Massri A, Doll HM, Sousa AMM, Wray GA, Schmidt E, Silver D. (2025) A humanspecific enhancer fine-tunes radial glia potency and corticogenesis. Nature 643, 1321-1332. [also in bioRxiv 588953]; PMID: 38645099
2. Gao Y†, Dong Q†, Arachchilage KH†, Risgaard RD, Sheng J, Syed M, Schmidt DK, Jin T, Liu S, Knaack S, Doherty D, Glass I, Levine JE, Wang D, Chang Q, Zhao X, Sousa AMM#. (2025) Multimodal analyses reveal genes driving electrophysiological maturation of neurons in the primate prefrontal cortex. Neuron, 113, 2490-2507. [also in bioRxiv 543460]; PMID: 37398253. Preview by Imaizumi and Pasca, Neuron 113, 2375-2377.
3. West NR, Arachchilage KH, Knaack S, Hosseini M, Risgaard R, MacGregor S, Kurumage P, Martinez JL, Zhang S-C, Wang D, Sousa AMM, Bhattacharyya A. (2025) Single-nucleus analysis reveals oxidative stress in Down syndrome basal forebrain at birth. Alzheimer’s & Dementia 21, e70445. [also in bioRxiv 636750]; PMID: 40667939
4. Bhattacharrya A, de la Torre-Ubieta L, Zhu Y, Head E, Swarup V, Sousa AMM. (2025) Development of molecular neuropathology in Down syndrome across the lifespan. The Journal of Neuroscience 45, e1365252025. PMID: 41224669
5. Li Z†, Kaur N†, Santpere G†, Muchnik SK†, Sindhu SK, Qi C, Shibata M, Clément O, Klarić TS, de Martin X, Luria V, Cho H, Li M, Shibata A, Tebbenkamp ATN, Ma S, Han W, Kim SK, Pochareddy S, Duy PK, Xing X, Bao Y, Xu X, Gladwyn-Ng IE, Cullen HD, Paolino A, Fenlon LR, Kozulin P, Suárez R, Risgaard RD, Gulden FO, Karger A, Suzuki IK, Hirata T, Gobeske KT, Richards LJ, Sousa AMM, Heng JI, Sestan N. (2026) Adaptive evolution of gene regulatory networks in mammalian neocortical neurons. Nature, in press. [also inbioRxiv 652233]
6. Kim S-K, Cherskov A, Sindhwani A, Choi S-H, Kim H, Li M-L, Zhang M, Mato-Blanco X, Liu Y, Micali N, Young DM, Estacion M, Nadkarni A, Luria V, Sindhu SK, Chatterjee I, Shibata A, Liang D, Cho H, Park S, Spajic A, Kovner R, Chen RJ, Risgaard RD, Li X, Pochareddy S, Karger A, Huttner A, Morozov YM, Daadi EW, Colantuoni C, Gobeske KT, Ely JJ, Hof PR, Daadi MM, Sherwood CC, Duque A, Ma S, Sousa AMM, Waxman SG, Rakic P, Santpere G, Sanders SJ, Sestan N. (2026) Human-specific features of the cerebellum and ZP2-regulated synapse development. Cell, in press. [also in bioRxiv, 674970]; PMID: 40964325
7. Risgaard RD†, Arachchilage KH†, Knaack SA†, Hosseini M†, Chen RJ, Kumarage P, Schmidt DK, Huang X, Sheng J, Wang CJ, Giusti E, Shuang Liu S, Zhang SC, Wang D, Bhattacharyya A, Sousa AMM# (2026). Molecular and cellular processes disrupted in the early postnatal Down syndrome prefrontal cortex. Science, in press. [also in bioRxiv, 662385]; PMID: 40631309

8.Franjic D*, Skarica M*, Ma S*, Arellano JI*, Tebbenkamp ATN*, Choi J, Xu C, Li Q, Morozov YM, Andrijevic D, Vrselja Z, Spajic A, Santpere G, Li M, Zhang S, Liu Y, Spurrier J, Zhang L, Gudelj I, Rapan L, Takahashi H, Huttner A, Fan R, Strittmatter SM, Sousa AMM, Rakic P, Sestan N. Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells. Neuron. 2022 Feb 2;110(3):452-469.

9. Shibata M*, Pattabiraman K*, Lorente-Galdos B, Andrijevic D, Kim SK, Kaur N, Muchnik SK, Xing X, Santpere G, Sousa AMM, Sestan N. Regulation of prefrontal patterning and connectivity by retinoic acid. Nature. 2021 Oct;598(7881):483-488.

10. Amiri A*, Coppola G*, Scuderi S*, Wu F*, Roychowdhury T*, Liu F, Pochareddy S, Shin Y, Safi A, Song L, Zhu Y, Sousa AMM, Gerstein M, Crawford GE, Sestan N, Abyzov A, Vaccarino FM. Transcriptome and epigenome landscape of human cortical development modeled in organoids. Science. 2018 Dec 14;362(6420).

11. Sousa AMM*, Zhu Y*, Raghanti MA, Kitchen RR, Onorati M, Tebbenkamp ATN, Stutz B, Meyer KA, Li M, Kawasawa YI, Liu F, Perez RG, Mele M, Carvalho T, Skarica M, Gulden FO, Pletikos M, Shibata A, Stephenson AR, Edler MK, Ely JJ, Elsworth JD, Horvath TL, Hof PR, Hyde TM, Kleinman JE, Weinberger DR, Reimers M, Lifton RP, Mane SM, Noonan JP, State MW, Lein ES, Knowles JA, Marques-Bonet T, Sherwood CC, Gerstein MB, Sestan N. Molecular and cellular reorganization of neural circuits in the human lineage. Science. 2017 Nov 24;358(6366):1027-1032.

12. Onorati M*, Li Z*, Liu F*, Sousa AMM*, Nakagawa N, Li M, Dell’Anno MT, Gulden FO, Pochareddy S, Tebbenkamp ATN, Han W, Pletikos M, Gao T, Zhu Y, Bichsel C, Varela L, Szigeti-Buck K, Lisgo S, Zhang Y, Testen A, Gao XB, Mlakar J, Popovic M, Flamand M, Strittmatter SM, Kaczmarek LK, Anton ES, Horvath TL, Lindenbach BD, Sestan N. Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia. Cell Rep. 2016 Sep 6;16(10):2576-2592.