# Core 2: GENETIC ENGINEERING CORE

> **NIH NIH P01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $379,125

## Abstract

ABSTRACT
The core objective of this Program Project is to define the relationships and interconnections between
hematopoiesis (the differentiation of hematopoietic stem cells, or HSCs) and the progression of cardiovascular
diseases (CVDs). To close this gap in knowledge, the Program Project will bring together field-leading
researchers to investigate currently unknown factors that mediate hematopoiesis following CVD processes
including myocardial infarction, atherosclerosis, and stroke, while also the dissecting contribution of these
factors to CVD progression. Therefore, there exists a great opportunity to leverage the capabilities imparted by
platform technologies like genome editing to engineer HSCs ex vivo and in mouse models of CVD to help
address these outstanding questions. Advances in genome-editing technologies have enabled researchers to
precisely alter DNA sequences and gene expression, allowing the rapid generation of biological models to test
functional significance of sequence variants. Genome editing enables the permanent heritable alteration of
genetic sequence by inducing targeted double-strand breaks (DSBs) in DNA at specified sequences. A
complementary approach called epigenome editing leverages the DNA targeting capabilities of the nuclease
platforms to transiently alter gene expression by recruiting heterologous effector domains capable of
modulating transcriptional states to regulatory regions of the genome, such as promoters or enhancers, without
the need for DSBs. Thus, the long-term goal of our Genome Engineering Core (Core 2) is to concurrently
develop and optimize genome- and epigenome editing technologies that will enable the rapid, safe, and
efficient editing of HSCs to elucidate the connection between hematopoiesis and CVD. Major objectives of
Core 2 include supporting the Projects of this proposal by optimizing experimental approaches, and providing
genome and epigenome editing reagents and expertise for key experiments of Projects 1 through 4. Core 2 will
also develop novel and innovative genome editing, epigenome editing, and lineage tracing platforms to
characterize genes, processes, and differentiation of HSCs. Specifically, Core 2 will support Projects 1-4 by
enabling efficient and specific genome editing strategies in mouse HSCs, by developing novel epigenome
editing reagents for use in HSCs, and by implementing and developing editing-based lineage tracing methods.
Successful optimization and development of editing in mouse HSCs pursued by this Core will expedite the
ability of Projects 1 through 4 to examine the relationships between hematopoiesis and CVD and more broadly,
these advances will be widely applicable to the study and therapeutic intervention of cardiovascular and
hematopoietic disorders, and the ex vivo genome and epigenome editing of HSCs.

## Key facts

- **NIH application ID:** 10469360
- **Project number:** 5P01HL142494-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** J. KEITH JOUNG
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $379,125
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469360

## Citation

> US National Institutes of Health, RePORTER application 10469360, Core 2: GENETIC ENGINEERING CORE (5P01HL142494-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10469360. Licensed CC0.

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