The Zhang lab is interested in the fundamental mechanisms of brain development with the ultimate goal of diagnosing and treating neurological disorders. Our current research integrates molecular and genetic approaches, and centers on the following directions:
- Genetics of human brain development. The massive expansion of neocortex in humans is associated with the highest cognitive functions, and genetic mutations that disrupt brain development can cause diseases such as autism and epilepsy. Using genetic and genomic approaches, we aim to investigate genetic variants that are associated with neurological disorders and understand fundamental mechanisms of brain development.
- Neurogenesis in the cerebral cortex. The six-layered neocortex is an evolutionary invention in mammals. We are interested in understanding how neurons are generated in the neocortex, how neuronal fates are specified, and how the neocortex is laminated. We are particularly interested in neurogenesis and neuronal migration processes, and use postmortem specimens and animal models to address these questions.
- Tracing neuronal cell lineages. All cells in the mouse brain (~100 million) originate from a single fertilized egg cell. Diverse neuronal cell types have been identified in mouse and human brains, but the molecular mechanisms underlying neuronal cell diversity and the lineage between cell types remain largely unclear. We are interested in tracing neuronal cell types and their lineages in mammalian brains.
- RNA splicing diversity and neural development. Alternative RNA splicing generates remarkable molecular diversity and in extreme cases enables a single gene to produce hundreds of different protein isoforms. What are the roles of alternative mRNA splicing in neurogenesis and neuronal differentiation? Single cell and bulk RNA sequencing analyses from us and others start to uncover cell type-specific mRNA isoforms and master splicing regulators during brain development. We showed that tight regulation of alternative splicing is required for human brain development.
At the University of Chicago, we are privileged to be part of the intellectually stimulating community. Our team will collaborate closely with labs within the Department of Human Genetics which has unusual strength in population genetics, comparative and functional genomics, and computational biology. We also share strong interests with peer labs in neuroscience, developmental and stem cell biology, and systems and single cell biology.