# Project 1 - Molecular and cellular determinants of hematopoietic clonal expansion

> **NIH NIH P01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $495,774

## Abstract

PROJECT SUMMARY
The human hematopoietic system is maintained by a pool of hundreds of thousands self-renewing
hematopoietic stem cells and multipotent progenitor cells. Recently, large genetic studies have revealed
the prevalence of somatic, clonal mutations, in blood cells of healthy individuals, a process referred as
clonal hematopoiesis (CH). The mechanisms by which a single hematopoietic cell carrying a CH-
related mutation expands at the expense of its normal counterparts is a major question with
implications to treat and monitor patients with CH-related complications. Another poorly understood
aspect of CH is its incomplete penetrance. While it is speculated that most humans by age 50 will have
accumulated one of these mutations in their long-lived hematopoietic progenitors, the degree of clonal
expansion among the population is tremendously varied. The cellular and molecular determinants of
this range of clonal behaviors are unclear. My lab has utilized high-resolution cellular barcoding
technologies to find that hematopoietic progenitor and stem cells exhibit remarkable heterogeneity in
their functional response to CH-associated mutations. Our analyses have also identified a number of
genes that characterizes the clones exhibiting hyper-competition. Based on these data, our project here
aims to understand the molecular mechanisms by which only a subset of hematopoietic progenitors
gains and maintains a competitive advantage. Additionally, our approach will take advantage of novel
physiologically relevant mouse models of CH where mutations can be directed to stem or progenitor cell
compartments. Our efforts here will be facilitated by state-of-the-art genomic and functional tools
uniquely suited to characterize heterogeneity at the single cell level. Successful accomplishment of the
aims of this project will provide new insight into the mechanisms of clonal dominance in states associated
with CH. Finally, our work will potentially identify actionable targets to manipulate clonal competition.

## Key facts

- **NIH application ID:** 10840856
- **Project number:** 5P01HL131477-07
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Fernando Camargo
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $495,774
- **Award type:** 5
- **Project period:** 2017-04-07 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840856

## Citation

> US National Institutes of Health, RePORTER application 10840856, Project 1 - Molecular and cellular determinants of hematopoietic clonal expansion (5P01HL131477-07). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10840856. Licensed CC0.

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