# Precision Medicine Approach:  Using genomic information to guide TBI treatment

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $471,651

## Abstract

Abstract
Concussive injury or mild/moderate TBI (mTBI) accounts for a large majority of the brain injuries in USA and
compromises neuronal function and cognitive abilities that can last for years. Neurons that survive the initial
insult show a decline in function, and one of the most intriguing aspects of mTBI is that many patients become
vulnerable to secondary injury or neurological disorders, which underlying instructions are hiding in alterations
of gene programs. The lack of information how TBI alters gene regulatory programs that govern pathogenesis
has precluded major advances in strategies to guide TBI therapeutics. Traditional medicine relies on
manifestations of symptoms and phenotypes rather than causative factors of the pathology. Instead, alterations
in the program of genes are likely causative factors of the pathology and can reveal therapeutic targets that can
support precision medicine initiatives. We have recently implemented the use of single-cell genomic analysis to
elucidate the impact of TBI on cell types, genes, pathways, and cell-cell interactions that can help inform on
novel targets for therapy. Our results from single-cell genomic analysis point to cell metabolism as a driver of
mTBI pathogenesis at the cell level and has helped us to prioritize thyroid hormone (important metabolic
modulator) as a potential therapeutic agent. The underlying hypothesis is that treatment with thyroid hormone
T4 can activate gene regulatory mechanisms that control functionality of circuits in brain regions important for
processing of higher order information. Leveraging the expertise of Dr. Xia Yang in genomics and systems
biology, and Dr. Fernando Gomez-Pinilla in TBI, we will utilize state-of-the-art parallel single cell sequencing
(drop-seq) to assess changes in gene expression in cells forming circuits in brain regions related to cognitive
processing. A unique aspect of our project is the implementation of highly sophisticated genomic procedures to
understand unsolved questions in the field of neural repair and plasticity and to monitor the efficacy of treatments,
using basic concepts of precision medicine. Astrocytes supply energy used by neurons, and they play a crucial
role in the incorporation of thyroid hormone from blood into neuronal cells, and according to our preliminary data,
astrocytes are highly vulnerable to TBI. We will modulate astrocyte activities to probe the role of astrocytes on
circuit reorganization after TBI and on the effects of thyroid hormone. Our studies have the promise to open new
avenues to mitigate mTBI pathology based on cell-specific functional aspects of gene regulation, which is also
a main premise for precision medicine initiatives.

## Key facts

- **NIH application ID:** 10832964
- **Project number:** 5R01NS111378-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Fernando Gomez-Pinilla
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $471,651
- **Award type:** 5
- **Project period:** 2020-01-15 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10832964

## Citation

> US National Institutes of Health, RePORTER application 10832964, Precision Medicine Approach:  Using genomic information to guide TBI treatment (5R01NS111378-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10832964. Licensed CC0.

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