Epigenetic regulation of axon regeneration in ischemic stroke

Active Project Grant Awarded Last action

Award ID
F31NS149788
Recipient
Awarding agency
Obligated
$42,804

Award facts

Assistance listing
93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders
Completion date 0% complete
Place of performance
Los Angeles, CA 90095, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Rapid degeneration of axons is a core feature of stroke that translates into life changing impairments. The loss of mobility in stroke patients presents a difficult challenge in functional recovery because axonal regeneration in the central nervous system is severely restricted. Existing treatments are limited to the first few hours after onset of stroke to promote functional recovery of damaged axons. However, a large majority of stroke patients are ineligible for these therapies, making stroke the leading cause of disability worldwide. Hence, there is an urgent need to develop novel strategies promoting axonal regeneration after injury to widen the recovery window. Surviving neurons intrinsically attempt to sprout new axons to replace damaged ones but face limited ability to regenerate. The molecular pathways promoting or inhibiting this intrinsic ability to regenerate after injury are not well understood. To gain further insight into this intrinsic regenerative ability, the goal of this project is to uncover the basic mechanisms of how an axonally injured mature neuron can shift into a pro-growth state after stroke to drive axonal regeneration linked with functional recovery. Decades of research have characterized a pro- degenerative protein, SARM1, that mediates axonal degeneration locally at axon terminals. Whether the intrinsic ability of a surviving neuron to sprout new axons requires targeting specific pro-degenerative or pro-growth molecules is unknown. Recent work from the hinman lab found that absence of SARM1 promotes survival of cortical neurons after ischemic stroke by activating a regenerative gene network implying SARM1-mediated axonal degeneration may inhibit surviving neurons from activating a dormant intrinsic regenerative program. The exact mechanism to activate these dormant regenerative programs remains unclear. Emerging studies and our RNA and assay for transposase accessible chromatin (ATAC) sequencing data suggest epigenomic modifiers can regulate coordinated changes in the transcriptome to activate regenerative gene networks. I will conduct a critical in-depth investigation of the molecular pathways driving neuronal survival and axon regeneration after stroke to test the hypothesis that a coordinated program of histone modifications acts as an epigenetic switch promoting these pro-growth pathways. I will receive training in techniques for the following aims. Aim 1 will identify epigenetically active genes mediating the intrinsic pro-growth shift of surviving neurons to regenerate axons after injury using stroke modeling with in vivo crispr interference. Aim 2 will reveal a 3D spatiotemporal map of axon regeneration linked with functional recovery using whole brain tissue clearing with dual neuronal tracer method and behavioral paradigms for functional motor and cognitive battery. I have selected my sponsor and mentors to provide training on each technical and intellectual aspect of the project, and on career advancement more broadly. Completing this project at ucla ensures access to a highly collaborative network of leading neuroscientists and help launch me into an independent career in regenerative neuroscience.

Quick answers

Who received award F31NS149788?

F31NS149788 was awarded to University Of California, LOS Angeles by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on December 1, 2026.

How much is award F31NS149788 worth?

$42,804 has been obligated on F31NS149788.

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