# The Platelet Transcriptome and Organ Failure After Injury: Discovering Molecular Biomarkers and Preventative Targets through Interrogating Novel RNA Modifications

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $403,750

## Abstract

Project Summary/Abstract
As a trauma surgeon-scientist and early stage investigator in the 5th year of an NIGMS mentored career
development award for the translational study of post-injury platelet function, I have developed expertise,
infrastructure, and made significant contributions to demonstrating that early platelet dysfunction after injury is
common, driven by changing physiology, and associated with later development of organ failure. This is
important because injury remains a leading cause of death worldwide, but advances in initial care have shifted
the burden of injury-related morbidity and mortality from early after injury to later, leaving two important
challenges:1) identifying injured survivors at highest risk of developing initial and sustained organ failure
leading to long-term morbidity and late mortality, and 2) discovering novel targets for early therapies to prevent
development of organ failure after injury.
Platelets contribute to organ failure through pathobiology in thromboinflammation. In similar diseases, platelet
transcriptomics has improved mechanistic understandings and driven exploration of platelet-based
therapeutics. Platelet megakaryocyte derived ribonucleic acids (RNAs) are stable in health, but modified by
physiological signals in disease. Importantly, platelets are anucleate and lack RNA synthesis, thus providing
the cleanest transcriptomic view of RNA modification in human biology. As such, my proposal seeks to re-
imagine how we understand, measure, and intervene on early alterations in platelets after injury by focusing on
the platelet transcriptome to explore prediction and prevention of organ failure among patients who initially
survive their injuries, and to identify RNA modification targets that can be tested in model systems by
addressing these knowledge gaps: 1) Identify the early platelet transcriptional landscape of severe injury and
its relationship to development and resolution of organ failure in longitudinal patient studies; 2) Define the
effect of platelet RNA modifications on platelet function in samples from patients with severe injury and in ex
vivo modified healthy platelets; 3) Develop ex vivo and in vitro model systems to manipulate clinically relevant
platelet RNA modifications as ultimate conduits to in vivo models and clinical testing. I will use feasible (next
generation sequencing, ribosome footprint profiling), and novel (sub-population sequencing, ex vivo transgenic
platelet model systems) methods to identify novel molecular biomarkers and preventative targets of
development of organ failure after injury, and innovate our understanding of physiologically driven RNA
modification through the ideal anucleate biology of platelets under the optimal acute physiologic changes of
injury. This K to R award transition proposal is NIGMS mission-focused by using basic research to increase
understanding of biological processes and lay the foundation for advances in disease diagnosis, treatment,
...

## Key facts

- **NIH application ID:** 10890084
- **Project number:** 5R35GM150656-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Lucy Zumwinkle Kornblith
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $403,750
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890084

## Citation

> US National Institutes of Health, RePORTER application 10890084, The Platelet Transcriptome and Organ Failure After Injury: Discovering Molecular Biomarkers and Preventative Targets through Interrogating Novel RNA Modifications (5R35GM150656-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10890084. Licensed CC0.

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