Luis F. Parada, Ph.D.,
UT Southwestern Medical Center, Dallas, TX

This laboratory has two areas of interest specific to spinal cord injury and to the eventual development of targeted therapeutics. Dr. Parada and his colleagues study the ras signal transduction pathway and have found that through ablation of a negative regulator, the rasGap, NF1, neurons constitutively activate the Trk/neurotrophin signaling pathway. Consequently neurons have more robust response to injury or loss of trophic factors. They have mutated NF1 in neurons of mice and demonstrated that upon injury by destruction of sensory afferent to the spinal cord, mice are able to recover function. This unprecedented result is the consequence of the capacity of spared neurons to hyper-sprout into the areas that have lost innervation. Now this laboratory is extending these results to gain insight into mechanism and possible therapeutic avenues.

The Parada laboratory has also become interested in the basis of myelin-based inhibition. Their experience with developmental neurobiology and the role of ephrins in axonal path finding has led them to investigate a potential role for these molecules in myelin repulsion of axons. They find strong evidence that myelin expresses ephrinB3 and that this is an active component of repulsion on ephA4 expressing corticospinal neurons. They are continuing to investigate the physiological relevance of this phenomenon with an aim toward developing "drugable" targets.