Neurogenesis occurs throughout life in the dentate gyrus of the hippocampus where adult neural stem cells proliferate and give rise to functionally integrated neurons. We are interested in understanding functions of adult neural stem cells and underlying molecular mechanisms regulating adult neurogenesis in the mature central nervous system. Our laboratory is using integrated approaches to study stem cells in animal models using technologies in molecular biology, cell biology, biochemistry, epigenetics, virology, histology, in vivo multiphoton confocal imaging, electrophysiology, mouse genetics and animal behaviors.

(1). Characterization of adult neural stem cells and neurogenesis: Adult neurogenesis occurs in unique microenvironment (niche) and recapitulates the complete neuronal developmental process in a mature central nervous system environment, including neuronal morphogenesis, migration, axon/dendritic development and synapse formation, maturation and maintenance. We are using retrovirus and mouse genetic based marking strategy to characterize the properties of adult neural stem cells and their development in vivo.

(2). Molecular mechanisms regulating adult neural stem cells and neurogenesis: We are interested in identifying both intrinsic and extrinsic mechanisms regulating adult neural stem cells and neurogenesis in vivo. We are currently focusing on investigating roles of several susceptibility genes for human mental disorders in the intrinsic regulation of different phases of adult neurogenesis, including MeCP2 (Rett Syndrome), NF1 (neurofibromatosis type 1) and DISC1 (Schizophrenia). We are also interested in activity-dependent extrinsic mechanisms originated from different local niche cells, including signaling from neurotransmitters and growth factors, and epigenetic regulation involving changes in histone and DNA methylation.

(3). Function of adult neurogenesis: We are characterizing contributions of newborn neurons at multiple levels in the adult brain, including single-cell electrophysiology in acute slices, local neuronal circuitry integration in vivo and contribution to specific animal behaviors. We are also generating animal models to examine the potential contribution of specific defects in adult neurogenesis to brain disorders.