# Endogenous circadian clocks regulate NG2-glia regenerative potential

> **NIH NIH K08** · CHILDREN'S RESEARCH INSTITUTE · 2023 · $182,403

## Abstract

PROJECT SUMMARY/ABSTRACT
Traumatic brain injury (TBI) is the leading cause of death and disability in patients aged 1-44 years. While there
is no treatment for TBI, one potential strategy is to harness the brain’s native capacity for cellular regeneration
to replace lost cells. NG2-glia, the largest population of regenerative cells in the adult CNS, can proliferate and
differentiate into multiple glial cell types; uncovering the molecular pathways regulating these NG2-glia
processes is a key step to develop future therapies for TBI. The candidate previously found that cortical NG2-
glia are regulated by the molecular circadian clock, a well-characterized 24-hr transcriptional-translational
feedback loop, with a key contribution by the clock gene Bmal1. However, the mechanism by which the clock
affects regenerative potential as well as the generalizability of this mechanism to other NG2-glia (e.g. white
matter NG2-glia) are unknown. In this proposal, the candidate hypothesizes that the NG2-glia endogenous
circadian clock directly governs molecular pathways to regulate regenerative potential, both in health and
disease. He will test this hypothesis with the following aims: 1) Determine the clock-dependence of cortical and
white matter NG2-glia proliferation and differentiation in the healthy brain and in response to TBI; 2) Identify the
clock-dependent molecular programs regulating cortical NG2-glia proliferation in the healthy and injured brain;
3) Define the differential expression of BMAL1 target genes during basal and injury-induced cortical NG2-glia
proliferation. Successful completion of these aims will identify the clock-dependent molecular pathways
underlying NG2-glia regenerative potential that will serve as future targets to manipulate post-TBI cellular
regeneration. Currently holding positions as Attending Physician in Critical Care Medicine at Children’s National
Hospital and Assistant Professor of Pediatrics at George Washington University School of Medicine and Health
Sciences, the candidate is committed to a career in academic medicine. With >75% protected time, as supported
by his institution, the candidate will be guided by his primary mentor (Vittorio Gallo) and co-mentors (Kazue
Hashimoto-Torii, Amita Sehgal, Regina Armstrong). He has access to laboratory space, supplies, and research
funding to carry out the proposed project. His career development plan is comprised of hands-on training and
didactics to accomplish his training goals, which includes technical and non-technical skills necessary for future
independence. From a technical aspect, he seeks training in in vitro techniques, human post-mortem tissue
evaluation, and omics sciences; there is a focus on the last, as his proposal uses translatomics and chromatin
mapping, two approaches ideally suited for investigating the changes in NG2-glia molecular programs induced
by the transcription factors comprising the circadian clock. Completion of his training plan will permit the...

## Key facts

- **NIH application ID:** 10807543
- **Project number:** 1K08NS131529-01A1
- **Recipient organization:** CHILDREN'S RESEARCH INSTITUTE
- **Principal Investigator:** Terry Dean
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $182,403
- **Award type:** 1
- **Project period:** 2023-09-26 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10807543

## Citation

> US National Institutes of Health, RePORTER application 10807543, Endogenous circadian clocks regulate NG2-glia regenerative potential (1K08NS131529-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10807543. Licensed CC0.

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