# Reactivation of Gamma Globin Expression in β-Hemoglobinopathies

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $39,112

## Abstract

ABSTRACT
 Oxygen delivery to the body’s tissues and organs is dependent on the qualitative and quantitative
features of hemoglobin, a tetrameric protein made up of two α- and two β-like subunits. β-
hemoglobinopathies are the most common monogenic disorders worldwide, and are defined based on
whether patients have quantitative (β-thalassemia) or qualitative (Sickle Cell Disease (SCD)) defects in β-
globin synthesis. Unfortunately, there are few treatment options for β-hemoglobinopathies. However, it
has been shown that an alternative β-like subunit, γ-globin, has the ability to compensate for the β-globin
defect in SCD and β-thalassemia. To date, few potential activators of γ-globin expression have been
discovered. Additionally, a recent study showed that steric hindrance at the γ-globin promoter (~150bp
upstream of the transcription start site) led to a decrease in γ-globin expression- implying the presence
of a γ-globin activator-binding region. Consistent with these findings, I have performed a pooled genome-
wide CRISPR activation screen that identified several novel candidate genes that may activate γ-globin
expression. In this proposal, I aim to validate these candidate γ-globin activators that I uncovered in my
screen and perform studies to determine the mechanism by which these candidate genes increase γ-
globin expression. Additionally, in my recent work I have found that a high percentage of slow cycling
human erythroid cells express γ-globin (termed F-cells) compared to erythroid cells with normal cycling
speeds. In this proposal, I also aim to dissect the impact of cell cycle speed regulation on γ-globin
expression. From this work I expect to uncover critical regulators of γ-globin. These newfound regulators
may lead to the development of novel therapeutics for β-hemoglobinopathies. Importantly, this proposal
will allow me to develop the skills, knowledge, and experience for a successful career in academic
research.

## Key facts

- **NIH application ID:** 10533403
- **Project number:** 1F31HL162544-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Ginette Theresa Balbin-Cuesta
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $39,112
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10533403

## Citation

> US National Institutes of Health, RePORTER application 10533403, Reactivation of Gamma Globin Expression in β-Hemoglobinopathies (1F31HL162544-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10533403. Licensed CC0.

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