Spinal cord injury can lead to damage of the corticospinal tract and thereby result in paralysis. My PhD project aims to promote regeneration of corticospinal tract in vivo because this is the key event to restore motor function.
The research strategy is based on an integrin engineering protocol that has produced substantial regeneration of sensory axons in the spinal cord. This was achieved by expressing integrins and their activator kindlin in injured sensory neurons. However, that approach will not work for corticospinal neurons because integrins are selectively blocked at the axon initial segment. We therefore plan to overcome the transport block though demolition of the axon initial segment and co-transduce the neurons with alpha9 integrin and kindlin. The hypothesis is that this combinatorial intervention could lead to successful regeneration of the corticospinal tract after spinal cord injury.
The research is conducted at the University of Cambridge (United Kingdom) and the Netherlands Institute for Neuroscience.
Nieuwenhuis B, Eva R. (2018) Linking axon transport to regeneration using in vitro laser axotomy. Neural Regeneration Research.
Nieuwenhuis B, Haenzi B, Andrews MR, Verhaagen J, Fawcett JW. (2018) Integrins promote axonal regeneration after injury of the nervous system. Biologicals Reviews. doi: 10.1111/brv.12398.
Mecollari V, Nieuwenhuis B, Verhaagen J. (2014) A perspective on the role of class III semaphorin signaling in central nervous system trauma. Front Cell Neurosci. doi: 10.3389/fncel.2014.00328.