# BLRD Research Career Scientist Award Application

> **NIH VA IK6** · VETERANS HEALTH ADMINISTRATION · 2024 · —

## Abstract

Research in the Chen lab focuses on alleviating the neurological sequelae of traumatic brain injury (TBI) and
ischemic stroke, which diminish our veterans’ quality of life. Our goals are to help identify and/or develop
pharmacologic agents that can leverage phylogenetically conserved tissue-repair mechanisms to alleviate acute
and secondary brain damage and sustain functional recovery.
TBI is a major concern for US military veterans. In TBI survivors, white matter injury is associated with long-term
functional deficits, including sensorimotor, cognitive, and psychiatric impairments. The Chen lab will continue to
develop restorative therapies that augment endogenous repair processes. Supported by VA Merit Review, we
found that the functional phenotypes of brain innate immune cells, including resident microglia and infiltrating
blood-borne macrophages, critically regulate the microenvironment in white matter and impact both white matter
injury and repair. We have recently identified salt-inducible kinase-1 (SIK1), an evolutionarily conserved protein
kinase, as a key molecular switch that governs the functional states of innate immune brain cells after TBI. Thus,
in the next four years, we will test the new hypotheses that genetic deletion or pharmacological inhibition of SIK1
improves white matter restoration and long-term TBI outcomes through dual mechanisms: 1) protecting against
early synaptic and axonal injury by inflammation-resolving microglia/macrophage responses, and 2) enhancing
chronic-stage white matter repair. Our preliminary data suggest that SIK1 inhibition not only reduces TBI-induced
sensorimotor and cognitive deficits, but also the psychiatric symptoms relevant to post-traumatic stress disorder
(PTSD). We believe that continued positive outcomes of this research will accelerate the development of novel
therapies to promote successful rehabilitation of veterans with TBI.
Stroke is a leading cause of long-term disability in elderly US veterans. Approximately 11,000 veterans are
hospitalized annually with new strokes. Although survival has increased with improvements in emergency care
and new recanalization therapy, the population with disabilities continues to climb. Optimal care of our veterans
will require therapies that not only ameliorate brain injury—but also lead to regeneration of brain tissue and
restoration of neurological function. Post-stroke immune responses have a substantial impact on the progression
of ischemic brain injury and brain recovery, but there are no clinical treatments that successfully harness the
restorative power of the immune system while also tempering inflammation-induced secondary injuries. The
reasons for this gap are multifactorial, but include a preclinical overemphasis on young adult animals, which do
not display the same pathophysiological mechanisms underlying brain ischemia as the aged. Using a clinically
relevant stroke model in 20-month old aging mice, our VA-funded research helped us make tw...

## Key facts

- **NIH application ID:** 10813046
- **Project number:** 5IK6BX006298-02
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Jun Chen
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-04-01 → 2030-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10813046

## Citation

> US National Institutes of Health, RePORTER application 10813046, BLRD Research Career Scientist Award Application (5IK6BX006298-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10813046. Licensed CC0.

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