More than 100 years of research has shown that the adult central nervous system is incapable of self-repair after injury or disease. Indeed, adults that suffer traumatic spinal cord injuries maintain chronic functional deficits that impact all aspects of their lives. However, increasing evidence suggests that the adult CNS retains some ability to initiate a growth program and functionally re-organize in response to activity, experience and mild trauma. In this proposal we have specifically isolated adult CNS neurons that have initiated an intrinsic growth response and after completing next generating sequencing (RNAseq), we have identified Plasticity Related Gene-3 (PRG3) as a novel cell autonomous mediator of axon growth. We have designed experiments to understand the molecular mechanisms underlying PRG3-mediated axon growth and plan to assess whether exploiting this molecular machinery can enhance functional recovery after severe acute and chronic experimental spinal cord injury in vivo. We believe that a comprehensive understanding of the intrinsic molecular mechanism that initiates and sustains spontaneous axon growth in adult CNS neurons can then be exploited to design novel therapies to repair the damaged spinal cord.
There are no effective treatments for spinal cord injury (SCI). The financial and emotional burden these injuries have on patients and their families highlights the urgent clinical need for potent and effective repair strategies. The aim of this proposal is to explore the molecular machinery that drives spontaneous recovery of function after SCI and determine whether this intrinsically mediated axon growth program can be exploited to more comprehensively restore function after severe acute and chronic SCI.
|Fink, Kathren L; López-Giráldez, Francesc; Kim, In-Jung et al. (2017) Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury. Cell Rep 18:2687-2701|
|Fink, Kathren L; Cafferty, William B J (2016) Reorganization of Intact Descending Motor Circuits to Replace Lost Connections After Injury. Neurotherapeutics 13:370-81|
|Fink, Kathren L; Strittmatter, Stephen M; Cafferty, William B J (2015) Comprehensive Corticospinal Labeling with mu-crystallin Transgene Reveals Axon Regeneration after Spinal Cord Trauma in ngr1-/- Mice. J Neurosci 35:15403-18|