Molecular mechanisms of neuronal development in embryos and adults; Functions of risk genes in mental disorders
Dr. Ming’s laboratory centers on understanding the molecular mechanisms underlying neuronal development during both embryonic stages and in the adult brain, with a particular focus on the signaling events involved in cell morphogenesis, cell migration, axon/dendritic development and synapse formation. Dr. Ming is interesting in identifying basic mechanisms regulating neuronal development with the hope of critical knowledge of adult neurogenesis to harness the endogenous regenerative capacity for enhancing brain function and repair. She is also interested in the functions and mechanisms of risk genes for mental disorder in neuronal development and her laboratory aims to better understand mechanisms underlying mental disorders so that novel strategies for prevention and treatment are possible.
As a graduate student, Dr. Ming worked on signal transduction mechanisms underlying axon guidance using in vitro Xenopous culture neurons. Originally trained as a physician specialized in Maternal and Child Health, she has for the last ten years at her own Johns Hopkins laboratory continued to work on mechanisms underlying axon and dendritic growth and guidance with a focus on in vivo model systems, first with developing Xenopus embryos. The lab simultaneously began using adult neurogenesis in the mouse hippocampus as a new model system. Over the past decade Dr. Ming and her colleagues have described in detail the sequential developmental events of adult neurogenesis in young adult mice using retrovirus-mediated targeting and mouse genetics, from activation of quiescent neural stem cells, proliferation and survival of proliferating newborn progeny, to axon and dendritic development and sequential formation of GABAergic and glutamatergic synaptic inputs by newborn neurons. The team has introduced a number of technologies from other field into the adult neurogenesis studies that greatly facilitated the laboratory’s analysis, including retrovirus-mediated birth-dating and gain/loss-of-function analysis, clonal lineage-tracing of adult neural stem cells, advance imaging of intact cells in a large volume, and optogenetics. Another focus of Dr. Ming’s laboratory for the past decade has been the function and mechanisms of a risk gene for major mental disorder, Disrupted in Schizophrenia 1 (DISC1) that occurs in neuronal development. Dr. Ming and her colleagues have made several novel findings using adult hippocampal neurogenesis as a cellular model system. The team has identified multifaceted roles of DISC1 in regulating the development of newborn granule cells in the adult hippocampus, including axon/dendritic development and cell positioning and was the first to show a critical role of DISC1 in synapse formation at both presynaptic and postsynaptic sites. They discovered that a major intracellular signaling pathway, AKT-mTOR pathway is a target of DISC1 in regulating neuronal development and further identified an interplay between extrinsic GABA signaling and intrinsic DISC1 signaling in regulating the neural development during adult neurogenesis. Dr. Ming’s first RO1 application related to DISC1 rodent models will be major focus of the laboratory going forward, and will build on the accumulation of the team’s efforts in understanding both fundamental biology of adult neurogenesis and etiology/pathogenesis of major mental disorders.