# FOXO3 Regulation of Normal and Stress Erythropoiesis

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $423,118

## Abstract

SUMMARY
 Chronic oxidative stress exacerbates an array of erythroid disorders, including hemoglobinopathies,
polycythemia vera and anemia of inflammation; yet the mechanisms engaged by erythroid chronic stress-
response remain relatively unexplored. In addition, their impact on normal physiological processes is
unknown. Our focus has been on the homeostatic transcription factor FOXO3 which is essential for the
regulation of the erythropoiesis redox state. We showed recently that FOXO3 is critical for terminal
maturation and enucleation in erythropoiesis. On the other hand, our studies indicate that the loss of
FOXO3 improves significantly anemia in a model of ß-thalassemia that is a genetic disorder of erythroid
cells with redox imbalance at its core. Given the broad scope of FOXO3 functions, the extent of its impact
on erythropoiesis may depend on the context. Our overarching goal is to test the hypothesis that chronic
activation of FOXO3-mediated stress-response pathways contributes significantly to the deleterious
pathophysiology of erythroid disorders. To test this hypothesis we propose to employ novel quantitative
imaging methodologies, genomic high-throughput approaches, and in vitro cultures of human erythroblasts
and mouse models generated on pure genetic background combined with loss- and gain-of-function
approaches to achieve the following independent yet highly complementary and synergistic aims: (Aim 1):
To investigate mechanisms whereby FOXO3 regulates erythroblast enucleation; (Aim 2): To
elucidate the role of FOXO3 in β-thalassemic erythropoiesis. These combined studies will elucidate
how chronic activation FOXO3-mediated stress response may alter normal physiological processes and
aggravate β-thalassemia specifically and more broadly erythroid disorders.

## Key facts

- **NIH application ID:** 9843688
- **Project number:** 5R01HL136255-04
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** SAGHI GHAFFARI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $423,118
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843688

## Citation

> US National Institutes of Health, RePORTER application 9843688, FOXO3 Regulation of Normal and Stress Erythropoiesis (5R01HL136255-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9843688. Licensed CC0.

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