# Testing the tyrosine phosphatase SHP-2 as a novel brake on efferocytosis

> **NIH NIH F31** · WASHINGTON UNIVERSITY · 2021 · $23,673

## Abstract

PROJECT SUMMARY/ABSTRACT
 On a daily basis, we turnover billions of apoptotic cells that are removed by phagocytic cells, such as
macrophages. The processes of cell death and phagocytic clearance are vital to maintaining homeostasis and are
related to many disease pathologies. As atherosclerotic plaques develop, monocyte-derived macrophages infiltrate
vessel walls to remove cholesterol-rich lipoproteins and cellular debris, but these lipid-laden macrophages eventually
become impaired in their phagocytic activity and undergo apoptosis (a form of cell death) due to prolonged exposure
to inflammatory stimuli. Uncleared apoptotic cells eventually progress to secondary necrosis, and as their plasma
membranes become permeabilized, intracellular contents are released into the surrounding microenvironment, further
stimulating an inflammatory response. Advanced atherosclerotic plaques with large, inflammatory necrotic cores
develop as uncleared dead cells and debris accumulate within vessel walls. Thus, modalities are needed to enhance
the clearance of dead cells and promote inflammation resolution within advanced plaques. In addition to professional
phagocytes (such as macrophages, which are impaired in atherosclerotic lesions), non-professional phagocytes also
exist and participate in the clearance process, such as epithelial cells in the digestive tract and lung, or mesenchymal
cells during embryonic limb development. These non-professional phagocytes can play vital roles in maintaining
homeostasis, yet the potential of non-professional phagocytes to help in the clearance of atherosclerotic plaques has
not been addressed. Based on our preliminary studies, loss of the tyrosine phosphatase, SHP-2, enhances the
clearance of apoptotic cells by non-professional phagocytes such as fibroblasts in vitro. We propose to further test
the role of SHP-2 as a novel brake on the clearance of dead cells, and define the mechanism(s) and immunologic
responses underlying this phenotype. Further, we propose to test the role of SHP-2 in modulating atherosclerotic
plaque clearance in vivo. Understanding the role of SHP-2 in regulating the phagocytic process by different types of
phagocytes at homeostasis and in atherosclerotic plaques will provide important therapeutic opportunities for
atherosclerosis.

## Key facts

- **NIH application ID:** 10558953
- **Project number:** 7F31HL160134-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Shannon Kelley
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $23,673
- **Award type:** 7
- **Project period:** 2021-09-30 → 2024-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10558953

## Citation

> US National Institutes of Health, RePORTER application 10558953, Testing the tyrosine phosphatase SHP-2 as a novel brake on efferocytosis (7F31HL160134-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10558953. Licensed CC0.

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