Andre M. M. Sousa, PhD
Position title: Assistant Professor, Department of Neuroscience
Molecular and cellular mechanisms of human brain development and evolution.
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.
Bibliography URL: Google Scholar
Werling D*, Pochareddy S*, Choi J*, An JY*, Sheppard B, Peng M, Li Z, Dastmalchi C, Santpere G, Sousa AMM, Tebbenkamp ATN, Kaur N, Gulden F, Breen M, Liang L, Gilson M, Zhao X, Dong S, Klei L, Cicek AE, Buxbaum J, Adle-Biassette H, Thomas J-L, Aldinger KA, O’Day DR, Glass I, Zaitlen N, Talkowski M, Roeder K, State MW, Devlin B, Sanders S, Sestan N. (2020) Whole-genome and RNA sequencing reveal variation and transcriptomic coordination in the developing human prefrontal cortex. Cell Rep. 107489. Article
Vrselja Z*, Daniele S*, Silbereis J, Talpo F, Morozov YM, Sousa AMM, Tanaka B, Skarica M, Pletikos M, Kaur N, Zhuang Z, Liu Z, Alkawadri R, Sinusas AJ, Waxman S, Latham S, Sestan N. (2019) Ex vivo normothermic restoration of brain circulation and cellular functions hours postmortem. Nature 568, 336–343. Article
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. Article
Amiri A*, Coppola G*, Scuderi S*, Wu F*, Roychowdhury T*, Liu F, Pochareddy S, Shin Y, Safi A, Song L, Zhu Y, Sousa AMM, The PsychENCODE Consortium, Gerstein M, Crawford GE, Sestan N, Abyzov A, Vaccarino FM. (2018) The transcriptome and epigenome landscape of human cortical development modeled in brain organoids. Science 362, eaat6720. Article
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. Article
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. Article
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-TBK1 localization and mitosis in human neuroepithelial stem cells and radial glia. Cell Rep. 16, 1–17. Article
Pletikos M*, Sousa AMM*, Sedmak G*, Meyer KA, Zhu Y, Cheng F, Li M, Kawasawa YI, Sestan N (2014) Temporal specification and bilaterality of human neocortical topographic gene expression. Neuron 81, 321-32. Article
Kwan KY, Lam MMS, Johnson MB, Dube U, Shim S, Rasin MR, Sousa AMM, Fertuzinhos S, Chen JG, Arellano JI, Chan DW, Pletikos M, Vasung L, Rowitch DH, Huang EJ, Schwartz ML, Willemsen R, Oostra BA, Rakic P, Heffer M, Kostovic I, Judas M, Sestan N. (2012) Species-dependent post-transcriptional regulation of NOS1 by FMRP in the developing cerebral cortex. Cell 149, 899-911. Article
Kang HJ*,Kawasawa YI*, Cheng F*, Zhu Y*, Xu X*, Li M*, Sousa AMM, Pletikos M, Meyer KA, Sedmak G, Guennel T, Shin Y, Johnson MB, Krsnik Z, Mayer S, Fertuzinhos S, Umlauf S, Lisgo SN, Vortmeyer A, Weinberger DR, Mane S, Hyde TM, Huttner A, Reimers M, Kleinman JE, Sestan N. (2011) Spatio-temporal transcriptome of the human brain. Nature 478, 483-489. Article