Anne Jacobi, F.M. Kirby Neurobiology Center, Boston Children’s Hospital, Harvard Medical School, Harvard University, Boston, United States

Transcriptomic Screen to Identify New Genetic Pathways and Strategies to Promote Axon Regeneration after SCI

Funded in: 2018, 2019, 2020


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Problem: Interventional possibilities after SCI are suboptimal

Target: Compare singe cell transcriptomics of cells able and unable to regenerate for finding novel targets

Goal: Identify new therapeutic targets for SCI treatment to improve regeneration and recovery

 

Despite significant progress in trying to enhance nerve regeneration after spinal cord injury (SCI), today’s interventions are still suboptimal. With this project, we will implement a new strategy for finding novel targets to improve regeneration and recovery. Our work is based on recent studies showing that there are >40 types of retinal ganglion cells (RGC’s) in the mouse retina and that the types vary dramatically in their ability of survive following optic nerve crush (ONC) and to regenerate axons following manipulations such as the activation of the mTOR pathway. Activation of this pathway leads to strong regeneration after injury of only one or a few RGC subtypes and also promotes regeneration of some corticospinal neurons, whose axons innervate motorneurons. Building on this relationship, and on advantageous features of RGC’s and ONC, this study will characterize gene expression in resilient and vulnerable types of RGC’s after ONC with or without mTOR activation using advanced single cell transcriptomics. This cutting edge method examines the gene expression of individual cells in a given population and enables us to correlate expression differences of the RGC’s with their susceptibility to ONC and their ability to regenerate following mTOR activation. Genes that correlate with resilience or vulnerability in the ONC model will then be transferred to the SCI paradigm. Here we want to down- or upregulate their expression as appropriate, and investigate if this leads to improved regeneration and functional recovery. Combining this ONC to SCI workflow with the new technology of single cell transcriptomics we hope to identify new therapeutic targets for SCI treatment.