# Targeting Enzymatic Regulation of Fetal Hemoglobin Repression

> **NIH NIH P01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $2,174,057

## Abstract

Overall Abstract:
The ultimate goal of this research program is to provide safe, effective, accessible and durable disease
modification for sickle cell anemia (SCD) that will improve multi-organ pathophysiology and reduce early death.
Research studies support the premise that fetal hemoglobin is the most powerful natural inhibitor of sickle cell
disease pathophysiology, and that inactivating fetal γ-globin (HBG) gene repression would be therapeutic in
human patients. The goals of this proposal focus on the manipulation and specific targeting of the
transcriptional regulatory machinery that represses HBG genes during development. These studies are
devoted to the identification of new drug targets, the epigenetic enzyme components that comprise the
repression machinery, that will lead to γ-globin activation in the normally silenced HBG genes in adult erythroid
progenitor cells (Project 1), to the modeling, synthesis and development of safe, effective and exquisitely
specific therapeutic compounds that will be validated in vitro and in vivo in sickle cell disease model mice
(Projects 1 and 3), and for those leads that prove to be most efficacious, onward to detailed characterization in
the optimal model for human hemoglobinopathies, the baboon (Project 2) in preparation for human clinical
trials (Project 3). The projected impact for patients suffering from β-globinopathies is that these proposed HbF-
inducing therapies will be sufficiently robust so as to counter the devastating complications of these diseases
(stroke, acute chest syndrome and early death) with safety parameters that will permit universal access as well
as life-long use.

## Key facts

- **NIH application ID:** 10164849
- **Project number:** 5P01HL146372-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** James Douglas Engel
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,174,057
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10164849

## Citation

> US National Institutes of Health, RePORTER application 10164849, Targeting Enzymatic Regulation of Fetal Hemoglobin Repression (5P01HL146372-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10164849. Licensed CC0.

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