# Determining the conserved molecular mechanisms contributing to inflammation during Sepsis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2023 · $374,181

## Abstract

Project Summary
Worldwide it is estimated that over 6 million people die each year as a result of sepsis. There
are few clinical treatment options for patients, therefore, it is critical to determine the molecular
mechanisms that occur during sepsis in order to identity new targets for therapeutic intervention.
Here we identify the long noncoding RNA, GAPLINC, as a conserved gene between human and
mice that is highly expressed in macrophages. We show that GAPLINC knockouts are resistant
to LPS induced septic shock. The overall aim of this proposal is to determine how GAPLINC
contributes to the immune response that leads to septic shock. In Aim 1 we will utilize our
genetic mouse models to expand on our initial findings and determine what impact knockout or
overexpression of GAPLINC has in response to gram negative induced sepsis in vivo. In Aim 2
we will determine the molecular mechanisms utilized by GAPLINC to influence immune genes.
We will identify the minimal region within GAPLINC required to impact gene expression. We will
determine the complexes GAPLINC makes either with RNA or proteins to function and finally we
will identify any structural features within GAPLINC that mediates these interactions. In Aim 3
we will determine if GAPLINC is functionally conserved in humans by studying its role in
controlling immune genes in primary human monocyte derived macrophages. This project will
enable us to better understand the complex mechanisms that are at play during bacterial
induced sepsis. By focusing on GAPLINC we will identify a new layer of regulation during sepsis
providing us with new avenues for future drug development.

## Key facts

- **NIH application ID:** 10614537
- **Project number:** 5R01AI148413-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Susan Carpenter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $374,181
- **Award type:** 5
- **Project period:** 2020-05-14 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10614537

## Citation

> US National Institutes of Health, RePORTER application 10614537, Determining the conserved molecular mechanisms contributing to inflammation during Sepsis (5R01AI148413-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10614537. Licensed CC0.

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