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 understanding 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 basic mechanisms involved in signaling amplification and adaptation to guidance cues, two key and largely unexplored aspects of long-range chemotropic guidance. 

(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. We are currently examining the signal transduction mechanisms underlying growth cone responses to the inhibitory molecules associated myelin using biochemical and cell-biological approaches. We are also generating genetic animal models for axon regeneration studies with a focus on epigenetic regulation of intrinsic growth ability.

(3). Neuronal migration and nerve guidance of newborn neurons from neural stem cells in the adult brain: Adult neurogenesis recapitulates neural development processes in the mature central nervous system. We are particularly interested in intrinsic and extrinsic mechanisms regulating navigation of new neurons, including neuronal migration and axon and dendritic growth in the adult brain. 

(4). Understanding mechanisms of neurological diseases using pluripotent human stem cells: Stem cells, especially human stem cells, also provide unique tools to model diseases of the nervous system.  By introducing human diseases mutants into relevant cell types derived from human embryonic stem cells, we aim to establish models to understand disease mechanisms. In parallel, we have derived induced pluripotent stem cells (iPSCs) from fibroblasts of human patients to establish models of defined neurological diseases. We are particularly interested in degenerative neurological diseases (ALS, Huntington’s Disease) and psychiatric disorders (Schizophrenia, Autism).