# Determining the biological importance of SETBP1 functional domains to develop novel therapeutic approaches for myeloid leukemias

> **NIH NIH F32** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $68,562

## Abstract

PROJECT SUMMARY/ABSTRACT
This project aims to elucidate the mechanism of action of the proto-oncogene SETBP1 (SET-binding protein 1)
through analysis of functional domains and cell cycle markers (Aim 1), and to use this mechanistic data to identify
novel therapeutic targets (Aim 2). To elucidate the role of functional domains in SETBP1-driven leukemia and
cell proliferation, I will mutate these domains and test the ability of the perturbed constructs to promote the
leukemic phenotype in a hematopoietic colony forming unit assay and in vivo. I will also utilize targeted gene
expression analysis to understand how cell cycle regulators are perturbed in context of these functional domain
mutations. I propose to use our new mechanistic data and preliminary small molecule functional screening data
to conduct informed drug development in cell line models and patient samples. I will validate prospective drug
targets and combinations in a novel SETBP1-mutant CNL cell line model, and then assess the efficacy of the
best agents in patient samples using one of the largest repositories of CNL samples in the world.
The proposed project takes advantage of my expertise in in vitro and in vivo modelling, while affording me the
opportunity to develop new skills and a fundamental understanding of translational cancer biology. Regular input
from my co-sponsors and other cancer biologists at OHSU will provide me with critical feedback on my data and
generate ideas for innovative experiments. Dr. Maxson is a leading expert on the biology of CNL and
mechanisms of CSF3R-driven oncogenesis. She has substantial experience with cellular and molecular biology
techniques and investigating novel oncogenic mutations in leukemia, making her ideally suited to mentor me on
this project. My co-sponsor, Dr. Brian Druker, is a physician scientist and the director of the Knight Cancer
Institute. As a physician scientist and a pioneer of targeted cancer therapy, Dr. Druker can provide clinical context
for my work and help to ensure that I am addressing the most clinically relevant questions. Dr. Druker’s wealth
of expertise in therapeutic development is essential for Aim 2 of this proposal.

## Key facts

- **NIH application ID:** 10151561
- **Project number:** 5F32CA239422-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Sarah Ann Carratt
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,562
- **Award type:** 5
- **Project period:** 2019-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151561

## Citation

> US National Institutes of Health, RePORTER application 10151561, Determining the biological importance of SETBP1 functional domains to develop novel therapeutic approaches for myeloid leukemias (5F32CA239422-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10151561. Licensed CC0.

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