# Novel mechanisms of the glial response to traumatic brain injury: dissecting the role of Ets21c in a Drosophila model

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2020 · $32,610

## Abstract

PROJECT SUMMARY/ABSTRACT
Why the brain continues to undergo functional and histopathological decline after a traumatic injury is a central
question in the field of traumatic brain injury (TBI) research, and the answer has important implications for the
development of effective therapies. Despite the fact that TBI is a highly heterogeneous group of clinical brain
disorders, inflammation is observed in nearly all injuries and it is likely the key driver of long-term decline and
degeneration. This notion is supported by increasing evidence from classical degenerative diseases like
Alzheimer’s disease indicating a role for astrocytes and microglia in promoting long-term inflammation. In early
TBI, these cells have a supportive role in recovery but over time, their continued activation likely contributes to
inflammation and decline although our mechanistic understanding remains limited. In part, the foundational
work in the field of TBI research predates the advent of unbiased sequencing techniques; thus, the application
of these technologies to the study of TBI could reveal entirely novel genes and processes central to its
pathogenesis. Our lab recently developed a head-directed injury model of TBI in Drosophila, resulting in an
injury phenotype that captures the key features of mammalian disease including temporary loss of
consciousness, learning and memory impairments, brain degeneration and mortality. Results from a time
course RNA-sequencing study using our TBI model highlights the oncogenic transcription factor Ets21c as a
key player throughout injury response, based on its significant and persistent upregulation post-injury. Though
Ets21c expression is minimal at baseline, preliminary data confirms Ets21c is highly expressed in glia after
injury. Results from a pilot study show that Ets21c knockdown rescues survival post-TBI, suggesting a specific
role for Ets21c in regulating the pathogenic functions of glia. Thus, this application examines a novel role for
Ets21c in TBI, with the hypothesis that Ets21c drives long-term glial reprogramming to promote brain
inflammation and decline after TBI. The goal of this proposal is to elucidate the role of Ets21c in traumatic
injury by 1) characterizing Ets21c expression following traumatic brain injury, 2) determining the
functional, molecular and cellular consequences of Ets21c knockdown in TBI and 3) defining the glia-
specific transcriptional role of Ets21c in TBI pathogenesis. These studies will expand our understanding of
transcriptional reprogramming in glial in injury settings and provide a detailed molecular mechanism for further
study in higher animal models.

## Key facts

- **NIH application ID:** 10213003
- **Project number:** 5F31NS111868-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** China Byrns
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,610
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213003

## Citation

> US National Institutes of Health, RePORTER application 10213003, Novel mechanisms of the glial response to traumatic brain injury: dissecting the role of Ets21c in a Drosophila model (5F31NS111868-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10213003. Licensed CC0.

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