The intricate neural network formation during development is fundamental for proper brain functions. Damages to the central nervous system (CNS) in adult mammals are devastating because of the extremely limited regenerative capability of mature neurons in the adult CNS and restoration of connectivity is essential for functional recovery. My laboratory is interested in understanding the molecular and cellular mechanisms underlying neuronal navigation and regeneration during development and in adulthood.

(1). Signal transduction mechanisms underlying neuronal growth cone guidance: We are interested in the molecular mechanisms underlying long-range growth cone navigation by diffusible guidance cues. We have developed in vitro and in vivo model systems using developing Xenopus spinal neurons to investigate both short-term and long-term signaling events triggered by defined gradients of developmental guidance cues. We are particularly interested in using fluorescent imaging approaches to examine the basic mechanisms involved in signaling amplification and adaptation to guidance cues.

(2). Mechanisms regulating axon regeneration: Injured axons in the adult CNS do not spontaneously regenerate because of the inhibitory CNS environment and a decrease of the intrinsic ability to grow. With cultured postnatal mammalian neurons we are currently examining the signal transduction mechanisms underlying growth cone responses to the inhibitory molecules associated myelin using biochemical and cell-biological approaches. 

(3). Neuronal migration and nerve guidance of newborn neurons from adult neural stem cells in the adult brain: In collaboration with Dr. Hongjun Song’s laboratory, we have developed retrovirus-mediated “single-cell genetic” approach for birth-dating, marking and genetic manipulation of individual newborn neurons to examine their migration and axon/dendrite growth and guidance in the adult mouse brain in vivo. We are also developing multi-photon imaging approach to monitor the development of new neurons in vivo. We are particularly interested in the intrinsic and extrinsic mechanisms regulating navigation of new neurons from endogenous neural stem cells in the adult brain.

Our work is supported by grants from the NIH, March of Dimes, Klingenstein Fellowship Award in the Neuroscience, Sloan and Adelson Medical Research Foundation.