# Predictors of Low-risk Phenotypes after Traumatic Brain Injury Incorporating Proteomic Biomarker Signatures.

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $218,565

## Abstract

PROJECT SUMMARY
Traumatic brain injury (TBI) is a leading cause of death in the US, and treatment options are limited.
Therapeutic clinical trials in TBI have yielded disappointing results owing in part to the difficulty in accounting
for clinically important heterogeneity within TBI. Early delivery of therapy is essential after TBI to reduce
secondary brain injury, but unrestricted treatment of all brain injuries could be harmful. TBI stimulates a
complex cascade of immunologic responses, both centrally and peripherally. These peripheral immune
responses to TBI could serve as an early sensor of risk phenotype given the rapid, readily measurable
response in the blood. An improved ability to risk-stratify patients on admission will streamline patient selection
for aggressive interventions—such as invasive neuromonitoring—versus selection of those patients who can
safely be observed reducing potential harms.
Holly E Hinson, MD MCR is a Neurologist and Neurointensivist at Oregon Health and Science University where
she cares for patients with severe acute brain injury. The objective of this application is to develop supervised
learning models of actionable short- and long-term outcomes post-TBI and to interrogate if pre-specified
immunoregulatory proteins add predictive power to the models over clinical features alone. Her central
hypothesis is that immunoregulatory proteomic signatures improve our ability to classify a low-risk clinical
phenotype after TBI. Dr. Hinson’s preliminary data suggest peripheral cytokine levels are associated with
actionable clinical events acutely after TBI. The project employs a highly-sensitive, single molecule
immunoarray (SIMOA) to detect immunoregulatory proteins complemented with an unbiased proteomic
approach utilizing global discovery mass spectrometry. She will develop and assess a series of models
incorporating proteomic signatures to classify: acute progressive intracranial hemorrhage (Aim 1A), acute
neurologic deterioration (Aim 1B), and long-term outcomes measured by the 6-month Glasgow Outcome Scale
(Aim 2). She will develop these models in a well-defined, clinical trial population (development set), and test
their ability to correctly classify outcome in an independent, prospectively enrolled cohort at OHSU (test set).
Under a multidisciplinary team of expert mentors, the project will generate new insights into low-risk phenotype
recognition and outcome classification after acute TBI. The proposed patient-oriented research project will be
enhanced by a structured didactic program in the principles of predictive modeling and patient phenotyping
(including proteomics), which will provide Dr. Hinson with the critical skills she will need to conduct
independent, innovative translational clinical research in the field of neurotrauma.

## Key facts

- **NIH application ID:** 10898005
- **Project number:** 5K23NS110828-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Holly Elaine Hinson
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $218,565
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898005

## Citation

> US National Institutes of Health, RePORTER application 10898005, Predictors of Low-risk Phenotypes after Traumatic Brain Injury Incorporating Proteomic Biomarker Signatures. (5K23NS110828-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10898005. Licensed CC0.

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