# Targeting Clonal Hematopoiesis of Indeterminate Potential using Human Genetics

> **NIH NIH DP5** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $432,500

## Abstract

Project Summary
Age is the dominant risk factor for most chronic diseases; yet mechanisms by which aging confers
risk are largely unknown. One unifying feature of aging diseases as diverse as cardiovascular
disease and cancer is the acquisition of somatic mutations in hematopoietic stem cells (frequently
DNMT3A, TET2, JAK2), termed Clonal Hematopoiesis of Indeterminate Potential (CHIP). I will
leverage human genomics to identify pathways underlying CHIP acquisition, clonal expansion
and disease. Why only some individuals develop CHIP, why only some CHIP clones expand, and
why only a minority of CHIP carriers develop disease is presently unknown. I hypothesize that
germline genetic variation contributes to CHIP acquisition, clonal expansion and disease. I
propose to (1) identify CHIP in existing genome sequencing data and perform genetic association
analyses of CHIP in >800,000 individuals and evaluate how CHIP-associated variants alter
human hematopoietic stem cell function in in-vitro follow-up experiments. (2) Define the
determinants of CHIP clonal expansion and association with disease. (3) Identify gene expression
programs that cause clonal expansion and disease. Successful execution of these aims will
highlight therapeutic targets for the prevention of CHIP, clonal expansion and disease for which
no therapies currently exist. Such a CHIP therapeutic would potentially be an intervention for
multiple aging diseases. To succeed in these aims, I will receive significant institutional support
from MGH including funding, space, protected time and mentorship to establish my research
group. The Broad Institute will provide access to leading-edge genomic resources. I will leverage
my unique position at the interface of these two scientific communities to establish a leading
research program focused on CHIP. Having completed rigorous training in genomics,
cardiovascular biology, and clinical medicine, I am now poised to leverage these skills, resources
and mentorship to embark on my own independent research career without delay.

## Key facts

- **NIH application ID:** 10016727
- **Project number:** 1DP5OD029586-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Alexander Bick
- **Activity code:** DP5 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $432,500
- **Award type:** 1
- **Project period:** 2020-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016727

## Citation

> US National Institutes of Health, RePORTER application 10016727, Targeting Clonal Hematopoiesis of Indeterminate Potential using Human Genetics (1DP5OD029586-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10016727. Licensed CC0.

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