# Genome Core

> **NIH NIH U54** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2020 · $25,643

## Abstract

ABSTRACT
NUP98 rearrangements are observed in up to 10% of the childhood acute myeloid leukemia
(AML) and are associated with poor prognosis. The unmet clinical needs and the lack of an
effective targeted therapy to the NUP98-rearranged leukemias emphasize the need for novel
regimens.
Our central hypothesis is that NUP98-fusion oncoproteins harbor critical functional regions that
are essential to their leukemogenetic potential. We also expect that NUP98-fusions will drive
specific transcriptional networks, and provide potential vulnerabilities that can be exploited using
CRISPR-mediated genome editing approach. We will test our hypothesis using multiple levels
of CRISPR-mediated genetic screens covering genome-wide, target gene panel, and saturation
protein scan. In collaboration with the Project 1 and Project 2 in this proposal, the Genome
Editing Core will help provide critical insights into the molecular mechanisms by which NUP98-
fusion oncoproteins lead to the development of leukemia.
This work is innovative in that it will illuminate critical domains/motifs in NUP98-fusion
oncoproteins, a particularly malignant disease that currently has no effective therapy. We expect
that successful completion of this proposal will (1) establish a new genetic screen approach
“saturation CRISPR protein scan” for a sub-protein level functional domain discovery, and (2)
yield novel mechanistic information about the functional regions in the NUP98-fusion
oncoproteins. The impact of this research will be of significance because (1) it provides novel
therapeutic opportunities against the difficult-to-treat NUP98-rearranged leukemias, and (2) it
will help identify novel functional elements in fusion oncoproteins and their associated pathways
for future pharmaceutical targeting.

## Key facts

- **NIH application ID:** 10230525
- **Project number:** 3U54CA243124-01S2
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Charles G Mullighan
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $25,643
- **Award type:** 3
- **Project period:** 2019-09-19 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10230525

## Citation

> US National Institutes of Health, RePORTER application 10230525, Genome Core (3U54CA243124-01S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10230525. Licensed CC0.

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