Research Interests

Spinal Cord Injury: Therapeutic Effect of Olfactory Ensheathing Cell Transplantation

A major focus in the lab is to determine the cells and molecules that facilitate axonal regeneration after spinal cord injury. For a number of years we have studied the effects of olfactory ensheathing glial cell (OEC) transplantation following spinal cord injury. OECs are known to associate with olfactory receptor neurons that are generated throughout life and continually project their axons from the PNS (nose) into the CNS (olfactory bulb). Dr. Phelps and her students, in collaboration with the Edgerton Lab at UCLA, found that the transplantation of OECs above and below a complete spinal cord transection promotes axon regeneration and results in electrophysiological, anatomical, and behavioral changes in hindlimb function. Such findings suggest that OECs promote regeneration of mature axons and the reorganization of spinal circuitry, both of which contribute to sensorimotor function. Further, we have analyzed the effects of OEC transplantation on anatomical changes during the acute and chronic injury phases. Another aspect of the OEC project involves the use of in vitro injury models in which we showed that OECs promote axon regeneration on an inhibitory substrate by the secretion of brain-derived neurotrophic factor, and promote neurite outgrowth by direct cell-to-cell interactions.

Spinal Cord Development: The Role of Reelin Signaling in Neuronal Migration

Developmental studies in the lab focus on neuronal migration in the dorsal horn of the reeler spinal cord. Reelin, the protein absent in naturally occurring reeler mutants, is a large extracellular matrix molecule that binds to lipoprotein receptors (Vldl and Apoer2). Reelin signaling causes tyrosine phosphorylation of an intracellular adaptor protein Disabled-1, which then initiates a cascade of events that lead to correct neuronal positioning. We found that the loss of Reelin signaling causes hypersensitivity to thermal nociception and insensitivity to mechanical stimulation. Current experiments focus on dissecting the cellular defects that underlie this unusual combination of nociceptive defects.