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Bart Nieuwenhuis



Email: bn246@cam.ac.uk
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Research

Injury to the brain and spinal cord has devastating consequences because adult neurons in the central nervous system (CNS) do not regenerate. My research aims to enhance the axon regeneration capacity of CNS neurons by using gene therapy.

Gene therapy

Gene therapy has advanced a lot in the past two decades. Gene therapy involves delivering a missing- or a protective gene into cells to treat a genetic disorder or acquired condition. Adeno-associated viral (AAV) vectors are carriers of genes that are the preferred choice for gene delivery in the eye, brain and spinal cord. AAVs have the benefit to turn on therapeutic genes for a long period of time. There are two important components that regulate the effectiveness of AAVs: 1) the outer-layer of the carrier that determines which type of cells are going to be hit and; 2) a DNA regulatory unit, called a promoter, that determines whether and how strongly the packaged gene will be turned on. Identifying the optimal outer-layer and promoter for each brain region has a crucial impact on how well gene therapy works, and can ultimately depict whether a treatment will be successful or unsuccessful. My research aims to optimize the delivery of transgenes in the spinal cord (corticospinal tract) and eyes (retinal ganglion cells) using AAVs.

Improving axon regeneration

In order to achieve functional recovery after injury, it is important to identify the strongest genes that drive long-range axonal regeneration. Most screenings are based on neurite outgrowth in a cell-culture dish, while axon regeneration is a different cellular process. We use a laser to injure neurons that are placed in a cell-culture dish to investigate potential axon regeneration targets. This injury model examines specifically the intrinsic axon regeneration response, and allows the investigation of individual genes or synergistic combinations. Identified therapeutic genes can next be taken forward in pre-clinical models of traumatic CNS injuries by using gene therapy.

BIOSKETCH

Bart Nieuwenhuis is a Research Associate at the University of Cambridge and the Netherlands Institute for Neuroscience. His research is supported by neurobiology and injury experts within the European ERA-NET neuron network. Bart completed his PhD in Clinical Neurosciences at the University of Cambridge. He also graduated in Neurosciences (MSc, cum laude) and Biomedical Sciences (BSc) at the VU University Amsterdam.

Publications

Nieuwenhuis B, Eva R. (2018) ARF6 and Rab11 as intrinsic regulators of axon regeneration. Small GTPases. doi: 10.1080/21541248.2018.1457914 – Download PDF

Nieuwenhuis B, Eva R. (2018) Linking axon transport to regeneration using in vitro laser axotomy. Neural Regeneration Research. doi:10.4103/1673-5374.228716Download PDF

Nieuwenhuis B, Haenzi B, Andrews MR, Verhaagen J, Fawcett JW. (2018) Integrins promote axonal regeneration after injury of the nervous systemBiologicals 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.