Regenerative Neurobiology Research Interests

We are interested in the general area of nerve injury and repair with the long-term goal of uncovering the molecular basis of neurite growth, axon guidance and target recognition, both during development and after injury. The multidisciplinary experimental approach that we follow incorporates concepts and tools from cell and molecular biology, biochemistry, mouse genetics, tissue engineering, electrophysiology, and nanobiology towards the generation of nerve repair strategies. Our research projects aim at uncovering the basic cellular and molecular mechanisms underlying the biology of nerve growth, and the implementation of improved nerve repair strategies.

Molecular Biology of Nerve Regeneration

Axonal guidance and outgrowth is governed by the integration of multiple attractive and repulsive signals resulting in activation of intracellular signaling cascades that ultimately converge into cytoskeletal rearrangements. We are interested in understanding the biological relevance of guidance molecules and growth factors involved in the development of spinal cord circuits and the mechanisms that underlie the inhibition of spontaneous recovery in the adult CNS after injury. Guidance molecules such as the eprhins/Eph receptors and neurotrophins activate the Ras intracellular signaling. Ras-mediated pathways participate in multiple aspects of neural development and function. In studying how this pathway is regulated in neurons we recently uncovered that NF-1 loss in sensory DRG neurons endows these cells with enhanced capacity for spontaneous growth after injury.

Directing and Enticing CNS and PNS Nerve Regeneration

Regenerative failure in the adult CNS results in permanent sensory-motor deficits. This sensory loss and paresis is due to a reduced intrinsic growth capacity of postnatal neurons and the presence of chondroitin proteoglycans and myelin-associated inhibitors at the injury site. Our previous work has demonstrated that in vivo gene transfer of Fibroblast Growth Factor-2 and Nerve Growth Factor induced axonal regeneration and functional recovery of chronically injured primary nocioceptive fibers, demonstrating that the inhibitory nature of the adult CNS parenchyma could be transformed from inhibitory to promoting of axonal regeneration. We are now extending such findings by incorporating guidance cues in repair strategies for gap injuries, both in transected peripheral nerves and in the damaged spinal cord.

In recent years, the emerging discipline of brain-machine interfaces has made significant progress towards developing a neurally controlled robotic prosthetic arm. A natural extension of directed peripheral nerve regeneration has been the development of a novel neuro-electrical interface for peripheral nerves, rather than cortical tissue, for the control of arm and hand prosthetics, capable of providing sensory feedback to the user. Our current efforts are placed in modifying our biosynthetic nerve implant to house micro-electrodes capable of recording and stimulating individual axons in vivo. Furthermore, in collaboration with Dr. Ray Baughman, Nanotechnology Institute at UTD, we are testing carbon nanotubes as substrates for cellular growth and as an electrical or electrochemical interface.