Decoding Human Brain Evo-Devo

The human brain has undergone profound multi-dimensional remodeling throughout evolution, including expanded brain volume, increased cortical gyrification, enhanced neuronal complexity, and significantly protracted development.

These features form the structural and developmental foundation for higher cognition, while increasing susceptibility to cognitive disorders such as Autism, Schizophrenia, and Alzheimer's Disease.

Using an evo-devo perspective, we integrate multi-species platforms, multi-scale omics data, deep learning, and AI models to study human brain uniqueness and disease risk.

Research directions

Cross-species comparison of brain features

Evo-devo Mechanisms Underlying Uniqueness of Human Brain

Focused on "What makes us human," we systematically profile human-specific characteristics and dissect their molecular and cellular mechanisms through cross-species and cross-development comparisons. Previously, we identified multi-faceted human-specific features, including distinct cell types, dopamine-secreting interneurons, and the expression regulation of language-related genes, and discovered the GALP signaling pathway as a key driver of prefrontal cortex expansion (Science 2022, 2023). Current research aims to address remaining unknowns, such as the regulatory networks driving protracted brain maturation, how this prolonged window impacts plasticity and functional networks, and the precise control of the assembly of human-specific neural circuits. We are combining comparative genomics with spatiotemporal multimodal profiling to understand how genomic variants and regulatory remodeling synergistically influence neuronal maturation and circuit assembly, tracing the evolutionary origins of higher-order cognitive functions from molecules to circuits.

Multimodal data and neural network model diagram

In silico Modeling of Human Brain Evo-Devo

The formation of the human brain's unique structure and developmental patterns stems from systemic remodeling of gene regulatory networks rather than single-point mutations. Similarly, cognitive disorders involve complex mechanisms coupling multiple genes, pathways, and scales. To deeply understand these regulatory laws and their causal links to disease susceptibility, high-dimensional integration of multi-scale information is essential. Leveraging the rapid accumulation of cross-species multi-omics data, we aim to build and integrate resources spanning the "molecule-cell-connectivity" scales. By fusing multi-modal data with deep learning algorithms and Large Language Model frameworks, we are developing digital models of human brain evolution and development. This approach enables the systematic screening and interpretable prediction of key developmental regulators and potential pathogenic elements, which are then validated experimentally to form a closed-loop discovery process.

Evolutionary medicine diagram for brain disorders

Evolutionary Medicine for Brain Disorders

Evolution has shaped natural heterogeneity in disease susceptibility across populations and species. This heterogeneity is not noise but a vital clue for understanding disease mechanisms and guiding interventions. For instance, we discovered that the primate-specific methyltransferase METTL7B confers neuroprotection, likely representing an adaptive response to the increased vulnerability to aging and AD in primates (Neuron 2022). Our laboratory is currently utilizing our multi-species platform to systematically analyze the key cell types and molecular pathways driving evolutionary differences in disease susceptibility. Based on these insights, we aim to develop novel, translatable therapeutic strategies and intervention targets for aging and cognitive disorders.

Join us

We are seeking enthusiastic Postdoctoral Fellows to join our research on Brain Evo-Devo, Multi-omics, and AI.

Postdoctoral Fellow

Candidates should hold or be nearing completion of a Ph.D. or equivalent degree in Bioinformatics, Computational Biology, Statistics, Biology, Medicine, or related fields. A good publication record, including at least one first-author paper in a mainstream international journal, is anticipated. A research background in neuroscience, developmental biology, or evolutionary biology is highly preferred. Good English communication and writing skills are required.

Email CV

Biological Research Building A
Institute of Neuroscience, CEBSIT, Chinese Academy of Sciences
320 Yue Yang Road, Shanghai 200031, China