Andre M.M. Sousa

Position title: Assistant Professor


Phone: (608) 890-0875

Research Interests - Molecular and cellular mechanisms of human brain development and evolution

Visit the Sousa Lab

The development of the human brain is a long and complex process that is precisely choreographed through tightly regulated transcriptional programs. Proper regulation of these programs is necessary for developing the numerous functionally distinct regions and cell types of the brain. Since the human brain exhibits morphological, physiological, and neural circuitry differences compared to other species, including other primates, it logically follows that many of these programs are human-specific. Due to both the evolutionarily distance from humans and the different social, cognitive, and motor abilities of classical model organisms, our capability to elucidate human-specific developmental programs has been limited, thus restricting our understanding of the human brain’s unique morphology, physiology, and connectivity. Importantly, uncovering this knowledge has far-reaching biomedical implications, as human-specific molecular and cellular mechanisms are involved not only in producing the most distinct aspects of human cognition and behavior, but also may underlie psychiatric and neurodevelopmental disorders.

Our lab aims to identify and characterize the molecular and cellular mechanisms that govern human brain development and evolution, and to apply that knowledge towards understanding neurodevelopmental and psychiatric disorders.

To achieve this goal, we apply a multifaceted approach that combines:

1) Functional genomic studies to identify genes that are critical for proper neurodevelopment and have conserved or human-specific expression profiles. We are also interested in deciphering the regulatory logic of genes with human-specific expression profiles.

2) Developmental neurobiology studies that combine induced pluripotent stem (iPS) cells, mouse genetic models, and postmortem human and NHP brains to characterize the functions of those candidate genes in the development of the brain.

3) Molecular and cellular biology studies that inform the biological processes that are disrupted by alterations in those genes, particularly the ones that are associated with neurodevelopmental and neuropsychiatric disorders.

Selected Publications

Bibliography URL: Google Scholar

(*equal contribution; #corresponding author)

Gao Y*, Dong Q*, Arachchilage KH*, Risgaard RD, Sheng J, Syed M, Schmidt DK, Jin T, Liu S, Doherty D, Glass I, BDRL, Levine JE, Wang D#, Chang Q#, Zhao X#, Sousa AMM#. (2023) Multimodal analysis of neuronal maturation in the developing primate prefrontal cortex.
biorXiv 543460.

Ma S*, Skarica M*, Li Q, Xu C, Risgaard RD, Tebbenkamp ATN, Mato-Blanco X, Kovner R, Krsnik Z, de Martin X, Luria V, Martí-Pérez X, Liang D, Karger A, Schmidt DK, Gomez-Sanchez Z, Qi C, Gobeske KT, Pochareddy S, Debnath A, Hottman CJ, Spurrier J, Teo L, Boghdadi AG, Homman-Ludiye J, Ely JJ, Daadi EW, Mi D, Daadi M, Marín O, Hof PR, Rasin M-R, Bourne J, Sherwood CC, Santpere G, Girgenti MJ, Strittmatter SM#, Sousa AMM#, Sestan N#. (2022) Molecular and cellular evolution of the primate dorsolateral prefrontal cortex.
Science 377, abo7257.

Shibata M*, Pattabiraman K*, Lorente-Galdos B, Andrijevic D, Kim S-K, Kaur N, Muchnik S, Xing X, Santpere G, Sousa AMM, Sestan N. (2021) Regulation of Prefrontal Patterning, Connectivity and Synaptogenesis by Retinoic Acid.
Nature 598, 483-488. [also in bioRxiv 891036].

Zhu Y*, Sousa AMM*, Gao T*, Skarica M*, Li M*, Santpere G, Esteller-Cucala P, Juan D, Ferrandez-Peral L, Golden FO, Yang M, Miller DJ, Marques-Bonet T, Kawasawa YI, Zhao H, Sestan N. (2018) Spatiotemporal transcriptomic divergence across human and macaque brain development.
Science 362, eaat8077.

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, Edles MK, Ely JJ, Elsworth JD, Horvath TL, Hof PR, Mane SM, Noonan JP, State MW, Lein ES, Knowles JA, Marques-Bonet T, Sherwood CC, Gerstein MB, Sestan N. (2017) Molecular and cellular reorganization of neural circuits in the human lineage.
Science 358, 1027-1032.

Sousa AMM*, Meyer KA*, Santepere G, Gulden FO, Sestan N. (2017) Evolution of the human nervous system function, structure, and development.
Cell 170, 226 – 247.

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 X-B, Mlakar J, Popovic M, Flamand M, Strittmatter SM, Kaczmarek LK, Anton ES, Horvath TL, Lindenbach BD, Sestan N. (2016) Zika virus disrupts phospho-TBK1localization and mitosis in human neuroepithelial stem cells and radial glia.
Cell Reports 16, 1–17.

Pletikos M*, Sousa AMM*, Sedmak G*, Meyer KA, Zhu Y, Cheng F, Li M, Kawasawa YI, Sestan N. (2013) Temporal specification and bilaterality of human neocortical topographic gene expression.
Neuron 81, 321-32.