How excess heme causes harmful iron-dependent cell death in sickle cell disease
Heme-induced metabolic stress drives ferroptosis in sickle cell disease
This work looks at how excess heme from broken red blood cells causes metabolic stress and an iron-driven form of cell death that can worsen sickle cell disease.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Augusta University NIH-funded |
| Lab location | 1 site (Augusta, United States) |
| Project ID | NIH-11174332 on NIH RePORTER |
What this research studies
Researchers will compare metabolite profiles from people with sickle cell disease and laboratory models to see how excess heme changes cellular metabolism. They will measure molecules such as 2‑oxoglutarate and L‑2‑hydroxyglutarate and examine related changes in gene regulation (histone methylation). Using mouse models and genetic tools like Nrf2 removal, the team will test whether these metabolic and epigenetic changes trigger ferroptosis, an iron-dependent cell death. The approach combines metabolomics, epigenetic analysis, and animal experiments to link biochemical changes to anemia and inflammation in SCD.
Who could benefit from this research
Good fit: Ideal candidates would be people with sickle cell disease who are willing to provide blood samples or participate in related clinical research tied to Augusta University.
Not a fit: People without sickle cell disease or those unwilling to provide samples or travel to the study site are unlikely to receive direct benefit from participation.
Why it matters
Potential benefit: If successful, this work could reveal new molecular targets to prevent iron-driven cell death and help reduce anemia and tissue damage in people with sickle cell disease.
How similar studies have performed: Previous studies have shown altered metabolites and oxidative stress in SCD, but linking 2OG/L2HG-driven epigenetic changes to ferroptosis is relatively new and still being tested.
Where this research is happening
Augusta, United States
- Augusta University — Augusta, United States (Active)
Researchers
- Principal investigator: Zhu, Xingguo — Augusta University
- Study coordinator: Zhu, Xingguo
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.