# Regulatory Role of Transferrin in Erythropoiesis and Iron Metabolism

> **NIH NIH R01** · SAINT LOUIS UNIVERSITY · 2024 · $679,795

## Abstract

ABSTRACT
The overall goal of our proposal is to investigate how iron metabolism and erythropoietic activity are interrelated,
and the mechanisms whereby dysregulation in one contributes to pathophysiology in the other. Roles for the two
transferrin receptors in these processes is clear; however, little is understood regarding the signaling properties
of their ligand, transferrin. Transferrin has long been recognized to deliver iron by binding to receptor, transferrin
receptor 1 (TFR1), present on all cells. More recently, a homologous receptor, TFR2, has been identified almost
exclusively on bone marrow and liver cells where it serves as a sensor of iron supply and a regulator of
erythropoiesis. We generated mice in which one or other of the two iron binding sites (N and C) was mutated,
and unable to take in iron. We observed striking differences in the regulation of iron metabolism and
erythropoiesis between these mice, demonstrating that each of lobes of transferrin has distinct signaling
properties. We present in this proposal new data demonstrating significant improvement in a mouse model of
the human disease β-thalassemia when iron is specifically bound to the N but not C lobe. We now devote our
attention to the mechanisms by which the two transferrin lobes exert their effects. We also explore the potential
of increasing N lobe TF as a potential treatment approach in ineffective erythropoiesis.

## Key facts

- **NIH application ID:** 10838572
- **Project number:** 5R01DK095112-07
- **Recipient organization:** SAINT LOUIS UNIVERSITY
- **Principal Investigator:** Robert E Fleming
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $679,795
- **Award type:** 5
- **Project period:** 2012-09-28 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10838572

## Citation

> US National Institutes of Health, RePORTER application 10838572, Regulatory Role of Transferrin in Erythropoiesis and Iron Metabolism (5R01DK095112-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10838572. Licensed CC0.

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