# The role of NCK1 in CSF3R-driven myeloproliferative neoplasms

> **NIH NIH F31** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $46,752

## Abstract

PROJECT SUMMARY
Colony Stimulating Factor 3 Receptor (CSF3R) is the primary receptor that drives the production of mature
neutrophils, activating signaling pathways to control proliferative and differentiation transcriptional programs.
CSF3R is recurrently mutated in poor-prognosis myeloproliferative neoplasms (MPNs). These mutations activate
CSF3R to enhance signaling through the JAK/STAT and MAPK pathways, resulting in an overproduction of
neutrophils. Drug development efforts have been focused on targeting the JAK/STAT activation. However, recent
studies have shown that enhanced MAPK pathway signaling may be equally important in disease pathobiology.
The precise mechanisms by which CSF3R activates the MAPK pathway are not fully understood. Identifying
novel players linking CSF3R to MAPK signaling would offer new therapeutic targets to explore, and allow for a
greater understanding of CSF3R signaling in normal and aberrant hematology.
Using a protein-protein interaction screen, I identified several CSF3R interacting partners that are known to
modulate MAPK pathway activation, including the signaling adapter NCK1. My preliminary data shows that NCK1
plays critical role in activation of the MAPK pathway and is required in CSF3RT618I-driven proliferation. I
hypothesize that NCK1 is an essential regulator of CSF3R-driven MAPK pathway activation and myeloid
proliferation. In Aim 1, I will map the essential regions and residues of CSF3R that are necessary for NCK1 to
potentiate MAPK activation, and establish a role for NCK1 in the control of myeloproliferative transcriptional
programs. In Aim 2 I will investigate how NCK1 controls myeloid differentiation, and determine whether NCK1
expression is required for the biogenesis of CSF3RT618I-driven myeloproliferative neoplasms in vivo. These
experiments will uncover the role of NCK1 in CSF3R-driven MAPK pathway activation and its role in normal and
aberrant hematopoiesis.
This fellowship will prepare me for the next stage in my academic career by providing me with new skills working
with in vivo models and transcriptomics, strengthening my understanding of hematologic disease, and supporting
my professional development. During the NRSA fellowship I will be mentored by Dr. Julia Maxson and Dr. Jeffrey
Tyner, who are exceptional advisors and well poised to support my growth and project development.

## Key facts

- **NIH application ID:** 10537617
- **Project number:** 1F31HL165919-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Breanna Nicole Maniaci
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537617

## Citation

> US National Institutes of Health, RePORTER application 10537617, The role of NCK1 in CSF3R-driven myeloproliferative neoplasms (1F31HL165919-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10537617. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*