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 DNA mutations that disrupt brain development can cause diseases such as autism and epilepsy. Using genetic and genomic approaches, we aim to investigate gene regulation in brain development and genetic causes of neurological disorders.
- Neuronal cell diversity and lineage in the cerebral cortex. The six-layered neocortex is an evolutionary invention in mammals. While diverse neuronal cell types have been identified among millions of brain cells, the molecular mechanisms underlying neuronal cell diversity and lineage remain largely unclear. We are interested in understanding how neurons are generated in the neocortex, how neuronal fates are specified, and how the neocortex is laminated.
- 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 mRNA splicing diversity 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 in mouse and human brains. We found that tight regulation of alternative splicing is required for human brain formation.
At the University of Chicago, we are privileged to be part of the intellectually stimulating community. Our team works 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.