Monday, February 16, 2026 2/16/2026

Deciphering the mechanism of SHIP1 regulation in human neutrophils

Award Number: R01GM143406
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2026

Group Awards By:

View Award Description

Deciphering the mechanism of SHIP1 regulation in human neutrophils - Research Summary Statement Immune cells interpret chemical cues in their environment and make decisions that control their fate. For example, human neutrophils often respond to signals by polarizing and migrating toward the chemical source. Critical for these cellular functions is the dynamic interplay between cell surface receptors, small GTPases, and the enzymes that synthesize phosphatidylinositol phosphate (PIP) lipids. This study aims to decipher the mechanisms the control communication between these different classes of signaling molecules at the plasma membrane. Using human neutrophils, we find that Cdc42 GTPase and a lipid phosphatase denoted SHIP1 trigger a molecular signal that propagates across the plasma membrane in the form of a traveling wave. This behavior, coined excitability, involves repetitive cycles of protein recruitment ON and OFF the membrane. The goal of this study is to determine how SHIP1 regulates the excitable signaling network by integrating signals derived from lipids and membrane tethered proteins. Using a variety of in vitro biochemistry techniques, including supported membrane technology and single molecule imaging, we will determine how lipid composition controls SHIP1 membrane association and phosphatase activity (Aim 1). Using factors that regulate the excitable signaling network in cells, we will reconstitute mechanisms that control SHIP1 membrane recruitment, release of autoinhibition, and activation (Aim 2). In parallel, we will use CRISPR based genome editing, optogenetics, and quantitative live cell imaging of fluorescent biosensors to elucidate how communication between PIP lipids and small GTPase is regulated by SHIP1. Using these tools we will determine the role SHIP1 serves as signaling network scaffold versus a lipid phosphatase (Aim 3). Overall, this study will unify membrane biophysics and cell biology to explain how PIP lipids, small GTPases, and SHIP1 synergistically control the excitable signaling network and cell migration in neutrophils. By unraveling how white blood cells sense, interpret, and respond to pathogenic signals we will fill a gap in knowledge concerning how these signaling molecules coordinate cellular movement with the underlying excitable network. This discovery could open doors for researchers to develop new therapeutics that can be used to modulate immune cell functions in ways that combat infection, inflammation, and cancer.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $379,161 )
2025	2025	UNIVERSITY OF OREGON	1776 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Biomedical Research and Research Training	001	5	6/3/2025	NON-COMPETING CONTINUATION	$301,384
2025	2025	UNIVERSITY OF OREGON	1776 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Biomedical Research and Research Training	003	5	7/16/2025	NON-COMPETING CONTINUATION	$0
2025	2025	UNIVERSITY OF OREGON	1776 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Biomedical Research and Research Training	004	5	7/18/2025	SUPPLEMENT FOR EXPANSION	$77,777
2025	2024	UNIVERSITY OF OREGON	1776 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Biomedical Research and Research Training	000	4	6/3/2025	TERMINATION	$0
2025	2024	UNIVERSITY OF OREGON	1776 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Biomedical Research and Research Training	002	4	7/16/2025	OTHER REVISION	$0
														Subtotal = $379,161

Issue Date FY: 2024 ( Subtotal = $372,433 )
2024	2024	UNIVERSITY OF OREGON	1776 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Biomedical Research and Research Training	001	4	7/16/2024	SUPPLEMENT FOR EXPANSION	$71,049
2024	2024	UNIVERSITY OF OREGON	1776 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Biomedical Research and Research Training	000	4	5/10/2024	NON-COMPETING CONTINUATION	$301,384
														Subtotal = $372,433

Issue Date FY: 2023 ( Subtotal = $301,384 )
2023	2023	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Biomedical Research and Research Training	000	3	5/16/2023	NON-COMPETING CONTINUATION	$301,384
														Subtotal = $301,384

Issue Date FY: 2022 ( Subtotal = $379,982 )
2022	2022	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Biomedical Research and Research Training	001	2	6/3/2022	SUPPLEMENT FOR EXPANSION	$78,598
2022	2022	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Biomedical Research and Research Training	000	2	5/17/2022	NON-COMPETING CONTINUATION	$301,384
														Subtotal = $379,982

Issue Date FY: 2021 ( Subtotal = $295,399 )
2021	2021	UNIVERSITY OF OREGON	1585 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Biomedical Research and Research Training	000	1	6/18/2021	NEW	$295,399
														Subtotal = $295,399

Grand Total All Awards = $1,728,359

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Deciphering the mechanism of SHIP1 regulation in human neutrophils

Award Number: R01GM143406

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer