# Systematic Genetic Dissection of Human Erythropoiesis

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2021 · $398,250

## Abstract

Project Summary/ Abstract
Humans vary considerably in the process of red blood cell production (erythropoiesis). Such variation
contributes to diseases, including numerous forms of anemia. Much of this variation is attributable to genetic
polymorphisms found in the population. However, as with most other complex diseases and traits, how such
variation impacts the process of erythropoiesis remains poorly understood. We have made tremendous
progress in beginning to decipher how human genetic variation impacts erythropoiesis during the first five
years of this grant from the NIDDK. We have pioneered the use of massively parallel reporter assays as an
approach to systematically dissect how non-coding genetic variation revealed from genome-wide association
studies (GWAS) functionally impacts transcriptional regulatory elements. We have also utilized CRISPR/Cas9
genome editing to bolster these findings in an endogenous context. In this competitive renewal application, we
aim to invigorate these studies and directly address how human genetic variation shapes the non-coding
genomic landscape of erythropoiesis. We will build upon our prior studies and use innovative new approaches
to ask these questions in primary human erythroid cells. We have recently conducted one of the largest GWAS
of erythroid traits and have identified over 1,800 distinct associated loci. We propose to utilize a number of
cutting-edge genomic tools that will allow us to gain important insights from these emerging large-scale genetic
studies. First, we aim to define putative causal variants underlying these associations and their functional
effects on the linked transcriptional regulatory elements. Second, we will systematically identify target genes
that may be affected by the regulatory elements harboring trait-associated variation. Finally, we will dissect
mechanisms of action by which a subset of these variants impact target genes and alter human erythropoiesis.
Not only will the proposed studies over the next five years significantly advance our understanding of human
erythropoiesis and related diseases, but this work will also serve as a paradigm for the systematic dissection of
other complex diseases and traits.

## Key facts

- **NIH application ID:** 10168519
- **Project number:** 5R01DK103794-08
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Vijay Ganesh Sankaran
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $398,250
- **Award type:** 5
- **Project period:** 2014-09-20 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168519

## Citation

> US National Institutes of Health, RePORTER application 10168519, Systematic Genetic Dissection of Human Erythropoiesis (5R01DK103794-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10168519. Licensed CC0.

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