# Hypoxic Injury and Tumor Formation in the C. elegans Germline

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $353,000

## Abstract

Project Summary/Abstract
Oxygen is critical for all aspects of human physiology. Accordingly, oxygen deprivation can significantly impair
or alter cellular functions, which can have devastating consequences to human health and viability.
Physiological events that block circulation and prevent the delivery of oxygen, such as heart attack or stroke,
cause lethal damage to affected tissues and comprise the leading cause of death and disability in Western
countries. In other physiological contexts, hypoxia can stimulate the growth and metastasis of cancer, another
human disease of considerable significance. For these reasons, there is substantial interest in developing
strategies for alleviating the pathological consequences of hypoxia. The nematode C. elegans has proven to
be a powerful model for investigating the mechanisms of hypoxic injury and for identifying potential strategies
for intervention. Enlisting the genetic advantages of C. elegans enabled mutagenic and RNAi screens which
together identified over 200 genes involved in hypoxic injury. This finding was enlightening because it
revealed that although the primary effect of oxygen deprivation is a simple failure of oxidative phosphorylation,
the ultimate repercussions of hypoxia are decided by a multitude of metabolic and cellular functions. By
discovering a plethora of new mechanisms involved in hypoxic injury C. elegans has provided a significant
contribution to the field. We believe C. elegans presents the most advantageous model for further
investigation into these mechanisms. The C. elegans germline harbors a diverse array of cell types and
physiological environments, therefore we reasoned that it might be a particularly useful context for
understanding novel ways in which hypoxia may impact cellular function. Our preliminary studies have
confirmed this, and established the potential of the germline to investigate three important aspects of hypoxic
injury. Our first aim is designed to identify general and cell-specific mechanisms of hypoxic injury. The second
aim is to characterize a novel mechanism for inducing resistance to hypoxic injury. And our third aim is to
understand how hypoxia causes tumors to form in the C. elegans germline. The powerful experimental tools
and interesting physiological properties of the germline offer unique advantages for achieving each of our
objectives. We expect these studies to be of considerable biomedical significance, as we will establish the
potential of general and cell-specific interventions, determine the potential for inducible mechanisms of hypoxia
resistance, and elucidate fundamental conserved mechanisms of hypoxia induced cancer formation.

## Key facts

- **NIH application ID:** 9920166
- **Project number:** 5R01GM129034-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Marc R Van Gilst
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $353,000
- **Award type:** 5
- **Project period:** 2018-08-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9920166

## Citation

> US National Institutes of Health, RePORTER application 9920166, Hypoxic Injury and Tumor Formation in the C. elegans Germline (5R01GM129034-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9920166. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*