# The role of the MBD2-NuRD complex in gamma-globin gene silencing

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2022 · $656,634

## Abstract

PROJECT SUMMARY
Studies of developmental regulation of globin gene expression have provided important mechanistic insight
into normal mammalian gene control and abnormal gene expression in diseases. Epigenetic mechanisms are
now recognized as central to globin gene regulation as well as dysregulation of genes in leukemia and other
cancers. This project is aimed at elucidating the key protein-protein interactions among components of the
MBD2-NuRD chromatin remodeling complex in the context of fetal β-type globin gene silencing in adult human
erythroid cells. The long term goal is to identify and validate targets for safe therapeutic activation of fetal
hemoglobin expression in sickle cell anemia and β-Thalassemia. This goal will be pursued through the
following collaborative aims: 1) To functionally define the roles of specific regions of MBD2 and NuRD complex
components in the ability of MBD2-NuRD to silence the fetal γ-globin gene in adult human erythroid cells and
2) to biophysically and structurally characterize interfaces critical for MBD-NuRD complex formation and
stability. The experimental approach employs a real-time iterative feedback between genome editing of key
protein interactions in adult erythroid cells in conjunction with structural studies of key protein-protein
interactions of MBD2, GATAD2A and CHD4 NuRD components using both standard NMR, and
crystallographic techniques as well as state-of-the-art paramagnetic relaxation enhancement (PRE) and
bioluminescence resonance energy transfer (BRET). The erythroid genes that are directly activated by
disruption of MBD2-NuRD and in turn relieve γ-globin gene silencing will be characterized by both RNA-seq
and ChIP-seq assays and bioinformatics analyses as well as ChIP assay validation. These experiments will
identify and validate proof of principle peptide and small molecule targets for future development of therapy of
sickle cell anemia and β-Thalessemia.

## Key facts

- **NIH application ID:** 10442549
- **Project number:** 5R01DK115563-05
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** GORDON D GINDER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $656,634
- **Award type:** 5
- **Project period:** 2018-08-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10442549

## Citation

> US National Institutes of Health, RePORTER application 10442549, The role of the MBD2-NuRD complex in gamma-globin gene silencing (5R01DK115563-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10442549. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*