# DEVELOPMENTAL BIOLOGY OF HUMAN ERYTHROPOIESIS

> **NIH NIH P01** · BOSTON CHILDREN'S HOSPITAL · 2021 · $1,994,675

## Abstract

Abstract/Summary
In this competitive renewal application of the Program Program grant >30 yrs in existence, diverse approaches
are used to address the singular theme of gene regulation in developing red blood cells. The Project Leaders
are united in their commitment to the developing red cell as an experimental system in which to make
fundamental biological discoveries that will inform our understanding of cell differentiation and directly impact
our capacity to treat disorders of the red cell, including congenital and acquired anemias. The Program
encompasses the most relevant vertebrate systems (human, mouse, and zebrafish) and employs
contemporary genetic approaches, including gene modification using CRISPR/cas9 and innovative genetic
screens. Deep, longstanding, and intensive interactions and collaborations among the Project Leaders ensures
synergy in the accomplishment of the proposed goals of the research. Project 1 (S.H. Orkin, Project Leader)
builds on prior groundbreaking work on the role of BCL11A in HbF repression and centers on the interaction of
BCL11A and other transcription factors with the nuclear matrix, the turnover of BCL11A protein and the search
for small molecules that destabilize the protein in erythroid cells, and cis-regulatory sites of BCL11A-binding in
the human β-globin cluster. In Project 2, H. Lodish (Project Leader) and his colleagues focus on the pathways
by which self-renewal of red cell progenitors is controlled. Project 3 (L. Zon, Project Leader) addresses the role
of transcription elongation in red cell gene expression and its intersections with signaling pathways. In Project
4 (D.E. Bauer, Project Leader), erythroid cell super-enhancer elements will be analyzed functionally with
innovative CRISPR/cas9 saturating mutagenesis, an approach recently pioneered in the Program. In Project 5
(B. Paw, Project Leader), new genes/proteins involved in iron and heme metabolism will be characterized for
their physiological roles in mouse/human/zebrafish systems. Each of the projects in this Program grant
addresses critical aspects of the expression program and function of erythroid cells. These studies are founded
on the premise that discoveries emerging from the proposed projects will provide new opportunities for the
design of novel approaches to the understanding and management of red blood cell disorders, including the
hemoglobinopathies (sickle cell disease and β-thalassemia), other congenital anemias, and acquired
conditions.

## Key facts

- **NIH application ID:** 10146443
- **Project number:** 5P01HL032262-39
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** STUART H ORKIN
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,994,675
- **Award type:** 5
- **Project period:** 1997-07-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146443

## Citation

> US National Institutes of Health, RePORTER application 10146443, DEVELOPMENTAL BIOLOGY OF HUMAN ERYTHROPOIESIS (5P01HL032262-39). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10146443. Licensed CC0.

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