Successful regeneration and functional recovery following nerve injury occurs partially in the peripheral nervous system whilst almost absent in the spinal cord. In instances of successful regeneration, an intrinsic pro-regenerative gene expression program is initiated following injury. Transcription factors are key regulators of this pro-regenerative gene expression program, my research aims to determine combinations of transcription factors which could promote regeneration in non-regenerating neurons.
Promoter regions of genes regulated after injury in regenerating and non-regenerating neurons were analysed to determine potential transcription factors that could be responsible for directing a pro-regenerative gene expression program. Potential transcription factors are screened alone and in combination in medium-throughput cellular screening and neurite outgrowth is quantified. Those transcription factors which promote neurite outgrowth in-vitro are subsequently over expressed via AAV viral vector mediated gene therapy in rodent spinal cord injury models and regeneration/ plasticity is assessed using functional testing, histological quantification and gene expression analysis. It is hoped that by determining intrinsic regulators of regeneration, this could one day be translated to treatments to improve recovery after traumatic central nervous system injury such as spinal cord and brain injury.
The research is funded by the Netherlands Organisation for Scientific Research (NWO) and the International Spinal Research Trust.
Callan Attwell graduated in Applied Science (BSc, distinction) at the HAN University for Applied Science, NL with research internships in iPSC differentiation & gene therapy. He is currently a PhD student at the Netherlands institute of Neuroscience in the Neuroregeneration group of Prof Joost Verhaagen, working under supervision of Dr Matthew Mason.
- Nitish D Fagoe, Callan L Attwell, R. Eggers, Lizz Tuinenbreijer, Dorette Kouwenhoven, J. Verhaagen, M.R.J. Mason Evaluation of Five Tests for Sensitivity to Functional Deficits following Cervical or Thoracic Dorsal Column Transection in the Rat PLoS One (2016)
- Nitish D Fagoe, Callan L Attwell, Dorette Kouwenhoven, J. Verhaagen, M.R.J. Mason Overexpression of ATF3 or the combination of ATF3, c-Jun, STAT3 and Smad1 promotes regeneration of the central axon branch of sensory neurons but without synergistic effects Human Molecular Genetics (2015)
- S A Hoyng, F De Winter, S Gnavi, L van Egmond, C L Attwell, M R Tannemaat, J Verhaagen, M J A Malessy Gene delivery to rat and human Schwann cells and nerve segments Gene Therapy (2015)