# Chemical Reprogramming of Traumatic Brain Injury

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $354,375

## Abstract

SUMMARY
Traumatic brain injury frequently leads to a loss of neurons and the disruption of neural circuitry. A fundamental
but unresolved challenge is how to restore lost neurons and repair the damaged neural circuits of the adult brain.
Neural stem cells persist and generate new neurons in the adult brain; however, their very restricted localization
renders them inadequate for regenerative purposes. The efficacy of transplanted stem cells is limited by the
survival and integration of induced neurons, as well as, a potential for tumorigenesis. The long-term goal of this
proposal is to define a new regenerative strategy for brain injury, which is to use a patient's endogenous glial
cells without transplantation. This strategy is based on our recent work showing that resident glial cells can be
transcriptionally reprogrammed into new neurons in the adult mouse brain. These reprogrammed neurons can
become mature and functionally integrate into the local neuronal network. Our preliminary data further revealed
that new neurons can also be induced by a pool of small molecules in the adult brain after traumatic injury,
suggesting that chemical biology can be applied to neural reprogramming in vivo. Three aims are proposed in
this application to further analyze the chemical reprogramming process: 1) to optimize the chemical composition
and to understand the underlying molecular mechanisms, 2) to examine cell origin, maturation, and connectivity
of chemically induced new neurons in the adult mouse brain after injury, and 3) to determine the biological effect
of chemical reprogramming on behavioral recovery after brain injury. The results of this proof-of-concept
research will lay the ground work for devising a potentially paradigm-shifting therapeutic strategy for brain injury.

## Key facts

- **NIH application ID:** 9942531
- **Project number:** 5R01NS099073-04
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Chun-Li Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $354,375
- **Award type:** 5
- **Project period:** 2017-06-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9942531

## Citation

> US National Institutes of Health, RePORTER application 9942531, Chemical Reprogramming of Traumatic Brain Injury (5R01NS099073-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9942531. Licensed CC0.

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