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.
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.