# Defining the metabolic regulation of erythropoiesis

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $42,094

## Abstract

PROJECT SUMMARY
The metabolic state of hematopoietic stem cells is an important contributor to self-renewal, however the
metabolic changes controlling the differentiation of hematopoietic stem cells to erythrocytes is poorly
understood. Here, I show preliminary data that that the malate-aspartate shuttle (MAS) impacts early
erythropoiesis. The MAS is a well-studied mechanism in cells that transfers electrons in the form of NADH from
the cytosol into the mitochondria, Specifically, disruption of the shuttle in vivo through conditional deletion of
one its enzyme in an erythroid progenitor leads to significant anemia. Accordingly, I hypothesize that the MAS
is required for redox homeostasis during early erythroid development and that failure of the MAS paves way for
ineffective erythropoiesis. AIM I works to determine which erythroid differentiation stages requires the MAS.
AIM II defines the molecular mechanism by which the MAS impacts erythropoiesis. For these, I am using both
in vivo mouse models and in vitro CD34+ hematopoietic stem and progenitor cells. Together, these aims
investigate whether reductive stress through the MAS during early erythropoiesis is an important contributor to
ineffective erythropoiesis.

## Key facts

- **NIH application ID:** 10826747
- **Project number:** 1F31HL172674-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Narges Pourmandi
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $42,094
- **Award type:** 1
- **Project period:** 2024-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10826747

## Citation

> US National Institutes of Health, RePORTER application 10826747, Defining the metabolic regulation of erythropoiesis (1F31HL172674-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10826747. Licensed CC0.

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