# Systematic Genetic Dissection of Human Erythropoiesis

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2024 · $645,733

## Abstract

Project Summary/ Abstract
Our lab has made substantial strides in understanding how human genetic variation affects erythropoiesis and
fetal hemoglobin (HbF) levels, both critical factors in conditions such as sickle cell disease and β-thalassemia,
as well as other forms of anemia. Utilizing cutting-edge genetic studies, we have mapped thousands of genetic
variants influencing red blood cell phenotypes and HbF levels. We have also functionalized these variants
through the use of innovative techniques such as massively parallel reporter assays and base editing in primary
human hematopoietic stem and progenitor cells that were developed with support we received over the past ten
years from this grant. In this competitive renewal application for this foundational grant, “Systematic Genetic
Dissection of Human Erythropoiesis,” we propose a deeper investigation into the genetic network regulating
human erythropoiesis and HbF expression. Specifically, we aim to 1) use massively parallel base editing to
pinpoint key nucleotide determinants of HbF-related regulatory elements; 2) chart high-resolution interaction
maps between these regulatory elements, their target genes, and other interactive genomic elements across
different stages of erythropoiesis; and 3) conduct multiplexed base editing of key transcription factors and
identified regulatory nucleotides to understand their genetic interactions. Our research will provide invaluable
insights into the intricate genetic mechanisms regulating erythropoiesis and HbF expression, potentially paving
the way for innovative therapeutic approaches for hemoglobinopathies. This project signifies a critical
foundational step in leveraging genetic knowledge for the development of clinical interventions in debilitating
hematological conditions.

## Key facts

- **NIH application ID:** 10881447
- **Project number:** 2R01DK103794-11
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Vijay Ganesh Sankaran
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $645,733
- **Award type:** 2
- **Project period:** 2014-09-20 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10881447

## Citation

> US National Institutes of Health, RePORTER application 10881447, Systematic Genetic Dissection of Human Erythropoiesis (2R01DK103794-11). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10881447. Licensed CC0.

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